Search results for: vitamin D toxicity

Authors: Yamma Rose, Kone Martine, Yonli Arsène, Wanko Ngnien Adrien

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Artisanal gold mining has seen a resurgence in recent years in Burkina Faso with its corollary of soil and water pollution. Indeed, in addition to visible impacts, it generates discharges rich in trace metal elements and acids. This pollution has significant environmental consequences, making these lands unusable while the population depends on the natural environment for its survival. The goal of this study is to assess the decontamination potential of Chrysopogon zizanioides on two artisanal gold processing sites in Burkina Faso. The cyanidation sites of Nebia (1Ha) and Nimbrogo (2Ha) located respectively in the Central West and Central South regions were selected. The soils were characterized to determine the initial pollution levels before the implementation of phytoremediation. After development of the site, parallel trenches equidistant 6 m apart, 30 cm deep, 40 cm wide and opposite to the water flow direction were dug and filled with earth amended with manure. The Chrysopogon zizanioides plants were transplanted 5 cm equidistant into the trenches. The mere fact that Chrysopogon zizanioides grew in the polluted soil is an indication that this plant tolerates and resists the toxicity of trace elements present on the site. The characterization shows sites very polluted with free cyanide 900 times higher than the national standard, the level of Hg in the soil is 5 times more than the limit value, iron and Zn are respectively 1000 times and 200 more than the tolerated environmental value. At time T1 (6 months) and T2 (12 months) of culture, Chrysopogon zizanioides showed less development on the Nimbrogo site than that of the Nebia site. Plant shoots and associated soil samples were collected and analyzed for total As, Hg, Fe and Zn concentration. The trace element content of the soil, the bioaccumulation factor and the hyper accumulation thresholds were also determined to assess the remediation potential. The concentration of As and Hg in the soil was below international risk thresholds, while that of Fe and Zn was well above these thresholds. The CN removal efficiency at the Nebia site is respectively 29.90% and 68.62% compared to 6.6% and 60.8% at Nimbrogo at time T1 and T2.

Keywords: chrysopogon zizanioides, in-situ phytoremediation, polluted soils, micropollutants

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Authors: Wilfred A. Abiaa, Chibundu N. Ezekiel, Benedikt Warth, Michael Sulyok, Paul C. Turner, Rudolf Krska, Paul F. Moundipa

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Mycotoxins are a wide range of toxic secondary metabolites of fungi that contaminate various food commodities worldwide especially in sub-Saharan Africa (SSA). Such contamination seriously compromises food safety and quality posing a serious problem for human health as well as to trade and the economy. Their concentrations depend on various factors, such as the commodity itself, climatic conditions, storage conditions, seasonal variances, and processing methods. When humans consume foods contaminated by mycotoxins, they exert toxic effects to their health through various modes of actions. Rural populations in sub-Saharan Africa, are exposed to dietary mycotoxins, but it is supposed that exposure levels and health risks associated with mycotoxins between SSA countries may vary. Dietary exposures and health risk assessment studies have been limited by lack of equipment for the proper assessment of the associated health implications on consumer populations when they eat contaminated agricultural products. As such, mycotoxin research is premature in several SSA nations with product evaluation for mycotoxin loads below/above legislative limits being inadequate. Few nations have health risk assessment reports mainly based on direct quantification of the toxins in foods ('external exposure') and linking food levels with data from food frequency questionnaires. Nonetheless, the assessment of the exposure and health risk to mycotoxins requires more than the traditional approaches. Only a fraction of the mycotoxins in contaminated foods reaches the blood stream and exert toxicity ('internal exposure'). Also, internal exposure is usually smaller than external exposure thus dependence on external exposure alone may induce confounders in risk assessment. Some studies from SSA earlier focused on biomarker analysis mainly on aflatoxins while a few recent studies have concentrated on the multi-biomarker analysis of exposures in urine providing probable associations between observed disease occurrences and dietary mycotoxins levels. As a result, new techniques that could assess the levels of exposures directly in body tissue or fluid, and possibly link them to the disease state of individuals became urgent.

Keywords: mycotoxins, biomarkers, exposure assessment, health risk assessment, sub-Saharan Africa

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Authors: Koteswara Rao Pagolu, Raghava Rao Tamanam

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The present study was aimed to find out the prevalence of DD's in Visakhapatnam, one of the north coastal districts of Andhra Pradesh, India during a span of five years. A cross-sectional investigation was held at District early intervention center (DEIC), Visakhapatnam from 2016 to 2020. To identify the pattern and trend of different DD's including seasonal variations, a retrospective analysis of the health center's inpatient database for the past 5 years was done. Male and female children aged 2 months-18 years are included in the study with the prior permission of the concerned medical officer. The screening tool developed by the Ministry of health and family welfare, India, was used for the study. Among 26,423 cases, children with birth defects are 962, 2229 with deficiencies, 7516 with diseases, and 15716 with disabilities were admitted during the study period. From birth defects, congenital deafness occurred in large numbers with 22.66%, and neural tube defect observed in a small number of cases with 0.83% during the period. From the side of deficiencies, severe acute malnutrition has mostly occurred (66.80 %) and a small number of children were affected with goiter (1.70%). Among the diseases, dental carriers (67.97%) are mostly found and these cases were at peak during the years 2016 and 2019. From disabilities, children with vision impairment (20.55%) have mostly approached the center. Over the past 5 years, the admission rate of down's syndrome and congenital deafness cases showed a rising trend up to 2019 and then declined. Hearing impairment, motor delay, and learning disorder showed a steep rise and gradual decline trend, whereas severe anemia, vitamin-D deficiency, otitis media, reactive airway disease, and attention deficit hyperactivity disorder showed a declining trend. However, congenital heart diseases, dental caries, and vision impairment admission rates showed a zigzag pattern over the past 5 years. This center had inadequate diagnostic facilities related to genetic disease management. For advanced confirmation, the cases are referred to a district government hospital or private diagnostic laboratories in the city for genetic tests. Information regarding the overall burden and pattern of admissions in the health center is obtained by the review of DEIC records. Through this study, it is observed that the incidence of birth defects, as well as genetic disease burden, is high in the Visakhapatnam district. Hence there is a need for strengthening of management services for these diseases in this region.

Keywords: child health screening, developmental delays, district early intervention center, genetic disease management, infrastructural facility, Visakhapatnam district

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Authors: Sakshi Gupta, Seema Joshi

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Thiosemicarbazones (TSCs) have garnered significant attention in coordination chemistry due to their versatile coordination modes and pharmacological properties. Mixed ligand complexes of TSCs represent a promising area of research, offering enhanced antimicrobial activities compared to their parent compounds. This review provides an overview of the synthesis, characterization, and antimicrobial properties of mixed ligand complexes incorporating thiosemicarbazones. The synthesis of mixed ligand complexes typically involves the reaction of a metal salt with TSC ligands and additional ligands, such as nitrogen- or oxygen-based ligands. Various transition metals, including copper, nickel, and cobalt, have been employed to form mixed ligand complexes with TSCs. Characterization techniques such as spectroscopy, X-ray crystallography, and elemental analysis are commonly utilized to confirm the structures of these complexes. One of the key advantages of mixed ligand complexes is their enhanced antimicrobial activity compared to pure TSC compounds. The synergistic effect between the TSC ligands and additional ligands contributes to increased efficacy, possibly through improved metal-ligand interactions or enhanced membrane permeability. Furthermore, mixed ligand complexes offer the potential for selective targeting of microbial species while minimizing toxicity to mammalian cells. This selectivity arises from the specific interactions between the metal center, TSC ligands, and biological targets within microbial cells. Such targeted antimicrobial activity is crucial for developing effective treatments with minimal side effects. Moreover, the versatility of mixed ligand complexes allows for the design of tailored antimicrobial agents with optimized properties. By varying the metal ion, TSC ligands, and additional ligands, researchers can fine-tune the physicochemical properties and biological activities of these complexes. This tunability opens avenues for the development of novel antimicrobial agents with improved efficacy and reduced resistance. In conclusion, mixed ligand complexes of thiosemicarbazones represent a promising class of compounds with potent antimicrobial activities. Further research in this field holds great potential for the development of novel therapeutic agents to combat microbial infections effectively.

Keywords: metal complex, thiosemicarbazones, mixed ligand, selective targeting, antimicrobial activity

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Authors: Amina Sa'id Muhammad, Asmau Ishaq Alhassan, Beba Raymond, Fatima Bello

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Severe acute malnutrition (SAM) remains a major killer of children under five years of age. Nigeria has the second highest burden of stunted children in the world, with a national prevalence rate of 32 percent of children under five. An estimated 2 million children in Nigeria suffer from severe acute malnutrition (SAM), and 3.9% of children in northwest Nigeria suffer from SAM, which is significantly higher than the national average of 2.1%. Community-Based Management of Acute Malnutrition (CMAM) has proven to be an effective intervention in the treatment of SAM in children using Ready-to-Use Therapeutic Food (RUTF). Ready-to-use therapeutic food (RUTF) is a key component for the treatment of Severe Acute Malnutrition. It contains all the energy and nutrients required for rapid catch-up growth and used particularly in the treatment of children over 6 months of age with SAM without medical complications. However, almost all RUTFs are currently imported to Nigeria from other countries. Shortages of RUTF due to logistics (shipping costs, delays, donor fatigue etc) and funding issues present a threat to the achievement of the 2030 World Health Assembly (WHA) targets for reducing malnutrition in addition to 2030 SDGs 2 (Zero Hunger), 3 (Good Health and Wellbeing), 12 (Responsible Consumption and Production), and 17 (Partnerships for the Goals), thus undermining its effectiveness in combating malnutrition On the other hand, the availability of human and material resources that will aid local production of RUTF presents an opportunity to fill in the gap in regular RUTF supply. About one thousand Nigerian children die of malnutrition-related causes every day, reaching a total of 361,000 each year. Owing to the high burden of malnutrition in Nigeria, the local production of RUTF is a logical step, that will ensure increased availability, acceptability, access, and efficiency in supply, and at lower costs. Objective(s): The objectives of this study were therefore, to formulate RUTF from locally available resources and to determine its energy and nutrients composition, incommensurate with the standard/commercial RUTF. Methods: Three samples of RUTF were formulated using locally available resources (soya beans, wheat, rice, baobab, brown-sugar, date palm and soya oil); which were subjected to various analysis to determine their energy/proximate composition, vitamin and mineral contents and organoleptic properties were also determined using sensory evaluation. Results: The energy values of the three samples of locally produced RUTF were found to be in conformity with WHO recommendation of ≥ 500 kcal per 100g. The energy values of the three RUTF samples produced in the current study were found to be 563.08, 503.67 and 528.98 kcal respectively. Sample A, B and C had protein content of 13.56% 16.71% and 14.62% respectively, which were higher than that of commercial RUTF (10.9%). Conclusions/recommendations: The locally formulated RUTF samples had energy value of more than 500 kcal per 100g; with an appreciable amount of macro and micro nutrients. The appearance, taste, flavor and general acceptability of the formulated RUTF samples were also commendable.

Keywords: energy, malnutrition, nutrients, RUTF

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Authors: V. E. Messerle, A. L. Mosse, O. A. Lavrichshev, A. N. Nikonchuk, A. B. Ustimenko

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One of the most serious environmental problems today is pollution by biomedical waste (BMW), which in most cases has undesirable properties such as toxicity, carcinogenicity, mutagenicity, fire. Sanitary and hygienic survey of typical solid BMW, made in Belarus, Kazakhstan, Russia and other countries shows that their risk to the environment is significantly higher than that of most chemical wastes. Utilization of toxic BMW requires use of the most universal methods to ensure disinfection and disposal of any of their components. Such technology is a plasma technology of BMW processing. To implement this technology a thermodynamic analysis of the plasma processing of BMW was fulfilled and plasma-box furnace was developed. The studies have been conducted on the example of the processing of bone. To perform thermodynamic calculations software package Terra was used. Calculations were carried out in the temperature range 300 - 3000 K and a pressure of 0.1 MPa. It is shown that the final products do not contain toxic substances. From the organic mass of BMW synthesis gas containing combustible components 77.4-84.6% was basically produced, and mineral part consists mainly of calcium oxide and contains no carbon. Degree of gasification of carbon reaches 100% by the temperature 1250 K. Specific power consumption for BMW processing increases with the temperature throughout its range and reaches 1 kWh/kg. To realize plasma processing of BMW experimental installation with DC plasma torch of 30 kW power was developed. The experiments allowed verifying the thermodynamic calculations. Wastes are packed in boxes weighing 5-7 kg. They are placed in the box furnace. Under the influence of air plasma flame average temperature in the box reaches 1800 OC, the organic part of the waste is gasified and inorganic part of the waste is melted. The resulting synthesis gas is continuously withdrawn from the unit through the cooling and cleaning system. Molten mineral part of the waste is removed from the furnace after it has been stopped. Experimental studies allowed determining operating modes of the plasma box furnace, the exhaust gases was analyzed, samples of condensed products were assembled and their chemical composition was determined. Gas at the outlet of the plasma box furnace has the following composition (vol.%): CO - 63.4, H2 - 6.2, N2 - 29.6, S - 0.8. The total concentration of synthesis gas (CO + H2) is 69.6%, which agrees well with the thermodynamic calculation. Experiments confirmed absence of the toxic substances in the final products.

Keywords: biomedical waste, box furnace, plasma torch, processing, synthesis gas

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Authors: Rabab Makki

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Bone mineral density and bone metabolism are affected by various factors such as genetic, endocrine, mechanical and nutritional. Our understanding of nutritional influences on bone health is limited because most studies have focused on calcium. This study investigated the dietary factors which are likely t contribute to Osteoporosis in Saudi post-menopausal women, and correlated it with BMD. This is a case controlled study involved 36 postmenopausal Saudi females selected from the Orthopedics and osteoporosis outpatient clinics, and 25 postmenopausal Saudi females as controls from the primary clinic of Military Hospital in Riyadh. The women were diagnosed as osteoporotic based on the BMD measurement at any site (left femur neck, right femur neck, left total hip or right total hip or spine). Both the controls and the Osteoporotics were over 50 years of age and BMI between 31-34 kg/m2 had 2nd degree obesity, and were not free from other problems such as diabetes, hypertension, etc. Subjects (osteoporotics and controls) were interviewed to called data on demographic characterstics, medical history, dietary intake anthropometry (height and weight) bone mineral density. Blood samples were collected from subjects (Osteoporotics and controls). Analysis of serum calcium, vitamin D, phosphate were done at the main laboratory at Military Hospital Riyadh, by the laboratory technician while BMD was determined at the department of Nuclear Medicine by an expert technician and results were interpreted by radiologist.Data on frequency of consumption of animal food (meat, eggs, poultry and fish) and diary foods (milk, yogurt, cheese) of osteoporotic was less than control. In spite of the low intake there was no association with BMD.In general, the vegetables and fruits were consumed less by the osteoporotics than control. The only fruit which had shown a significant positive correlation is banana with right and left hip BMD total probably due to high potassium and minerals content which likely to prevent bone resorption. Mataziz vegetables combination of wheat showed a significant positive correlation with the same site (total right and left hip). Both osteoporotics abd controls were consuming table sugar. (But the sweet intake showed a significant negative correlation with left neck femur BMD, suggesting sucrose increase urinary calcium loss. Both osteoporotic and controls were consuming Arabic coffee. A negative significant correlation between intake of Arabic coffee and BMD of right neck femur of osteoporosis patient was observed. It could be suggested that increased intake of fruits and vegetables, might promote bone density while high intake of coffee and sugars might affect bone density, no significant correlation was observed between BMD at any site and diary product. We can say the major risk factors are inadequate nutrition. Further studies are needed among Saudi population to confirm these results.

Keywords: osteoporosi, Saudia Arabia, Riyadh Armed Forces, postmenopausal women

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Authors: Md. Shoffikul Islam, Hongqing Hu

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Immobilizing trace elements by reducing their mobility and bioavailability through amendment application, especially biochar (BC), is a cost-effective and efficient method to address their toxicity in the soil environment. However, the low molecular weight organic acids (LMWOAs) in the rhizosphere could affect BC's efficiency to immobilize trace metals as the LMWOAs could either mobilize or fix metals in the soils. Therefore, understanding the BC's and LMWOAs' interaction mechanisms on metals stabilization in the rhizosphere is crucial. The present study examined the impact of BC derived from rice husk, tartaric acid (TA), and oxalic acid (OA), and the combination of BC and TA/OA on the changes of cadmium (Cd), lead (Pb), and zinc (Zn) among their geochemical forms through incubation experiment. The changes of zeta potential and X-ray diffraction (XRD) pattern of BC and BC-amended soils to investigate the probable mechanisms of trace elements' immobilization by BC under the attacks of TA and OA were also examined. The rice husk BC at 5% (w/w) was mixed with the air-dry soil (an Anthrosols) contaminated with Cd, Pb, and Zn in the plastic pot. The TA and OA each at 2, 5, 10, and 20 mM kg-1 (w/v) were added separately into the pot. All the ingredients were mixed thoroughly with the soil. A control (CK) treatment was also prepared without BC, TA, and OA addition. After 7, 15, and 60 days of incubation with 60% (w/v) moisture level at 25 °C, the incubated soils were determined for pH and EC and were sequentially extracted to assess the metals' transformation in soil. The electronegative charges and XRD peaks of BC and BC-amended soils were also measured. The BC, low level of TA (2 mM kg-1 soil), and BC plus the low concentration of TA (BC-TA2) addition considerably declined the acid-soluble Cd, Pb, and Zn in which BC-TA2 was found to be the most effective treatment. The trends were reversed concerning the high levels of TA (>5-20 mM kg-1 soil), all levels of OA (2-20 mM kg-1 soil), and the BC plus high levels of TA/OA treatments. BC-TA2 changed the highest amounts of acid-soluble and reducible metals to the oxidizable and residual fractions with time. The most increased electronegative charges of BC-TA2 indicate its (BC-TA2) highest metals' immobilizing efficiency, probably through metals adsorption and fixation with the negative charge sites. The XRD study revealed the presence of P, O, CO32-, and Cl1- in BC, which might be responsible for the precipitation of CdCO3, pyromorphite, and hopeite concerning Cd, Pb, and Zn immobilization, respectively. The findings demonstrated that the low level of TA increased metals immobilization, while the high levels of TA and all levels of OA enhanced their mobilization. The BC-TA2 was the best treatment in stabilizing metals in soil.

Keywords: biochar, immobilization, low molecular weight organic acids, trace elements contaminated soil

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Authors: Carlos Minguez, Christian F. Sagbay, Erika E. Ordoñez

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Guinea pigs (Cavia porcellus) play prominent roles as experimental models for medical research and as pets. However, in developing countries like South America, the Philippines, and sub-Saharan Africa, the meat of guinea pigs is an economic source of animal protein for the poor and malnourished humans because guinea pigs are mainly fed with forage and do not compete directly with human beings for food resources, such as corn or wheat. To achieve efficient production of guinea pigs, it is essential to provide insurance against vitamin C deficiency. The objective of this research was to investigate the effect of the partial replacement of alfalfa with fresh citrus pulp (Citrus sinensis) in a diet of guinea pigs on the growth performance, slaughter traits and mortality during the fattening period (between 20 and 74 days of age). A total of 300 guinea pigs were housed in collective cages of about ten animals (2 x 1 x 0.4 m) and were distributed into two completely randomized groups. Guinea pigs in both groups were fed ad libitum, with a standard commercial pellet diet (10 MJ of digestible energy/kg, 17% crude protein, 11% crude fiber, and 4.5% crude fat). Control group was supplied with fresh alfalfa as forage. In the treatment group, 30% of alfalfa was replaced by fresh citrus pulp. Growth traits, including body weight (BW), average daily gain (ADG), feed intake (FI), and feed conversion ratio (FCR), were measured weekly. On day 74, the animals were slaughtered, and slaughter traits, including live weight at slaughter (LWS), full gastrointestinal tract weight (FGTW), hot carcass weight (with head; HCW), cold carcass weight (with head; CCW), drip loss percentage (DLP) and dressing out carcass yield percentage (DCY), were evaluated. Contrasts between groups were obtained by calculated generalized least squares values. Mortality was evaluated by Fisher's exact test due to low numbers in some cells. In the first week, there were significant differences in the growth traits BW, ADG, FI, and FCR, which were superior in control group. These differences may have been due to the origin of the young guinea pigs, which, before weaning, were all raised without fresh citrus pulp, and they were not familiarized with the new supplement. In the second week, treatment group had significantly increased ADG compared with control group, which may have been the result of a process of compensatory growth. During subsequent weeks, no significant differences were observed between animals raised in the two groups. Neither were any significant differences observed across the total fattening period. No significant differences in slaughter traits or mortality rate were observed between animals from the two groups. In conclusion, although there were no significant differences in growth performance, slaughter traits, or mortality, the use of fresh citrus pulp is recommended. Fresh citrus pulp is a by-product of orange juice industry and it is cheap or free. Forage made with fresh citrus pulp could reduce about of 30 % the quantity of alfalfa in guinea pig for meat and as consequence, reduce the production costs.

Keywords: fresh citrus, growth, Guinea pig, mortality

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Authors: Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Kemal Aygun, Ecem Deniz Kırkpantur, Ozge Ecmel Onur

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Although the mechanism of action is not well known, Intravenous Lipid Emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that ILE probably separate the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high dose free fatty acids activating the voltage gated calcium channels in the myocytes. In this study, the effects of ILE treatment on digoxin overdose which are frequently observed in emergency departments was searched in an animal model in terms of cardiac side effects and survival. The study was carried out at Yeditepe University, Faculty of Medicine-Experimental Animals Research Center Labs in December 2015. 40 Sprague-Dawley rats weighing 300-400 g were divided into 5 groups randomly. As the pre-treatment, the first group received saline, the second group received lipid, the third group received DigiFab, and the fourth group received DigiFab and lipid. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest occurrence times were recorded. As no medication causing arrhythmia was infused, Group 5 was excluded from the statistical analysis performed for the comparisons of first arrhythmia and death time. According to the results although there was no significant difference in the statistical analysis comparing the four groups, as the rats, only exposed to digoxin intoxication were compared with the rats pre-treated with ILE in terms of first arrhythmia time and cardiac arrest occurrence times, significant difference was observed between the groups. According to our results, using DigiFab treatment, intralipid treatment, intralipid and DigiFab treatment for the rats exposed to digoxin intoxication makes no significant difference in terms of the first arrhythmia and death occurrence time. However, it is not possible to say that at the doses we use in the study, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the inter-comparisons of all the groups, the study should be repeated in the larger groups.

Keywords: arrhytmia, cardiac arrest, DigiFab, digoxin intoxication

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Authors: Emma O’ Keeffe, Helen Hughes, Peter McLoughlin, Shiau Pin Tan, Nick McCarthy

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Biosecurity is emerging as one of the most important issues facing the agricultural and forestry community. This is as a result of increased invasion from new pests and diseases with the main protocol for dealing with these species being the use of synthetic pesticides. However, these chemicals have been shown to exhibit negative effects on the environment. Seaweeds represent a vast untapped resource of bio-molecules with a broad range of biological activities including pesticidal. This project investigated both the antifungal and antibacterial activity of seaweed species against two problematic root rot fungi, Armillaria mellea and Heterobasidion annosum and ten quarantine bacterial plant pathogens including Xanthomonas arboricola, Xanthomonas fragariae, and Erwinia amylovora. Four seaweed species were harvested from the South-East coast of Ireland including brown, red and green varieties. The powdered seaweeds were extracted using four different solvents by liquid extraction. The poisoned food technique was employed to establish the antifungal efficacy, and the standard disc diffusion assay was used to assess the antibacterial properties of the seaweed extracts. It was found that extracts of the green seaweed exhibited antifungal activity against H. annosum, with approximately 50% inhibition compared to the negative control. The protectant activities of the active extracts were evaluated on disks of Picea sitchensis, a plant species sensitive to infection from H. annosum and compared to the standard chemical control product urea. The crude extracts exhibited very similar activity to the 10% and 20% w/v concentrations of urea, demonstrating the ability of seaweed extracts to compete with commercially available products. Antibacterial activity was exhibited by a number of seaweed extracts with the red seaweed illustrating the strongest activity, with a zone of inhibition of 15.83 ± 0.41 mm exhibited against X. arboricola whilst the positive control (10 μg/disk of chloramphenicol) had a zone of 26.5 ± 0.71 mm. These results highlight the potential application of seaweed extracts in the forestry and agricultural industries for use as biopesticides. Further work is now required to identify the bioactive molecules that are responsible for this antifungal and antibacterial activity in the seaweed extracts, including toxicity studies to ensure the extracts are non-toxic to plants and humans.

Keywords: antibacterial, antifungal, biopesticides, seaweeds

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Authors: Mansi Patel, Priti Mehta

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Background: Ionizing radiations have detrimental effects on humans, and the growing technological encroachment has increased human exposure to it enormously. So, the safety issues have emphasized researchers to develop radioprotector from natural resources having minimal toxicity. A substance having anti-inflammatory, antioxidant, and immunomodulatory activity can be a potential candidate for radioprotection. One such plant with immense potential i.e. Bamboo was selected for the present study. Purpose: The study aims to evaluate the potential of Indian bamboo leaves for protection against the clastogenic effect of gamma radiation. Methods: The protective effect of bamboo leaf extract against gamma radiation-induced genetic damage in human peripheral blood lymphocytes (HPBLs) was evaluated in vitro using Cytokinesis blocked micronuclei assay (CBMN). The blood samples were pretreated with varying concentration of extract 30 min before the radiation exposure (4Gy & 6Gy). The reduction in the frequency of micronuclei was observed for the irradiated and control groups. The effect of various concentration of bamboo leaf extract (400,600,800 mg/kg) on the development of radiation induced sickness and altered mortality in mice exposed to 8 Gy of whole-body gamma radiation was studied. The developed symptoms were clinically scored by multiple endpoints for 30 days. Results: Treatment of HPBLs with varying concentration of extract before exposure to a different dose of γ- radiation resulted in significant (P < 0.0001) decline of radiation induced micronuclei. It showed dose dependent and concentration driven activity. The maximum protection ~ 70% was achieved at nine µg/ml concentration. Extract treated whole body irradiated mice showed 50%, 83.3% and 100% survival for 400, 600, and 800mg/kg with 1.05, 0.43 and 0 clinical score respectively when compared to Irradiated mice having 6.03 clinical score and 0% survival. Conclusion: Our findings indicate bamboo leaf extract reduced the radiation induced cytogenetic damage. It has also increased the survival ratio and reduced the radiation induced sickness and mortality when exposed to a lethal dose of gamma radiation.

Keywords: bamboo leaf extract, Cytokinesis blocked micronuclei (CBMN) assay, ionizing radiation, radio protector

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Authors: Tanu Sharma, Bikramjit Singh Bajwa, Inderpreet Kaur

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Monitoring of groundwater in Tarn-Taran, Bathinda, Faridkot and Mansa districts of Punjab state, India is essential where this freshwater resource is being over-exploited causing quality deterioration, groundwater depletion and posing serious threats to residents. The present integrated study was done to appraise quality and suitability of groundwater for drinking/irrigation purposes, hydro-geochemical characteristics, source identification and associated health risks. In the present study, groundwater of various districts of Punjab state was found to be heavily contaminated with As followed by U, thus posing high cancerous risks to local residents via ingestion, along with minor contamination of Fe, Mn, Pb and F−. Most health concerns in the study region were due to the elevated concentrations of arsenic in groundwater with average values of 130 µg L-1, 176 µg L-1, 272 µg L-1 and 651 µg L-1 in Tarn-Taran, Bathinda, Faridkot and Mansa districts, respectively, which is quite high as compared to the safe limit as recommended by BIS i.e. 10 µg L-1. In Tarn-Taran, Bathinda, Faridkot and Mansa districts, average uranium contents were found to be 37 µg L-1, 88 µg L-1, 61 µg L-1 and 104 µg L-1, with 51 %, 74 %, 61 % and 71 % samples, respectively, being above the WHO limit of 30 µg L-1 in groundwater. Further, the quality indices showed that groundwater of study region is suited for irrigation but not appropriate for drinking purposes. Hydro-geochemical studies revealed that most of the collected groundwater samples belonged to Ca2+ - Mg2+ - HCO3- type showing dominance of MgCO3 type which indicates the presence of temporary hardness in groundwater. Rock-water reactions and reverse ion exchange were the predominant factors for controlling hydro-geochemistry in the study region. Dissolution of silicate minerals caused the dominance of Na+ ions in the aquifers of study region. Multivariate statistics revealed that along with geogenic sources, contribution of anthropogenic activities such as injudicious application of agrochemicals and domestic waste discharge was also very significant. The results obtained abolished the myth that uranium is only root cause for large number of cancer patients in study region as arsenic and mercury were also present in groundwater at levels that were of health concern to groundwater.

Keywords: uranium, trace elements, multivariate data analysis, risk assessment

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Authors: H. Li, L. Ji, J. Su

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Forward osmosis is an emerging technology for separation and has great potential in the concentration of liquid products such as protein, pharmaceutical, and natural products. In pharmacy industry, one of the very tough talks is to concentrate the product in a gentle way since some of the key components may lose bioactivity when exposed to heating or pressurization. Therefore, forward osmosis (FO), which uses inherently existed osmosis pressure instead of externally applied hydraulic pressure, is attractive for pharmaceutical enrichments in a much efficient and energy-saving way. Recently, coordination complexes have been explored as the new class of draw solutes in FO processes due to their bulky configuration and excellent performance in terms of high water flux and low reverse solute flux. Among these coordination complexes, ferric citrate complex with lots of hydrophilic groups and ionic species which make them good solubility and high osmotic pressure in aqueous solution, as well as its low toxicity, has received much attention. However, the chemistry of ferric complexation by citrate is complicated, and disagreement prevails in the literature, especially for the structure of the ferric citrate. In this study, we investigated the chemical reaction with various molar ratio of iron and citrate. It was observed that the ferric citrate complex (Fe-CA2) with molar ratio of 1:1 for iron and citrate formed at the beginning of the reaction, then Fecit would convert to ferric citrate complex at the molar ratio of 1:2 with the proper excess of citrate in the base solution. The structures of the ferric citrate complexes synthesized were systematically characterized by X-ray diffraction (XRD), UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Thermogravimetric analysis (TGA). Fe-CA2 solutions exhibit osmotic pressures more than twice of that for NaCl solutions at the same concentrations. Higher osmotic pressure means higher driving force, and this is preferable for the FO process. Fe-CA2 and NaCl draw solutions were prepared with the same osmotic pressure and used in FO process for BSA protein concentration. Within 180 min, BSA concentration was enriched from 0.2 to 0.27 L using Fe-CA draw solutions. However, it was only increased from 0.20 to 0.22 g/L using NaCl draw solutions. A reverse flux of 11 g/m²h was observed for NaCl draw solutes while it was only 0.1 g/m²h for Fe-CA2 draw solutes. It is safe to conclude that Fe-CA2 is much better than NaCl as draw solute and it is suitable for the enrichment of liquid product.

Keywords: draw solutes, ferric citrate complex, forward osmosis, protein enrichment

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Shwu-Ling Peng, Chiung-Man Tsai, Chia-Jui Weng

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Chronic micro-inflammation is a hallmark of many aging-related neurodegenerative and metabolic syndrome-driven diseases. In high glucose (HG) environment, reactive oxygen species (ROS) is generated and the ROS induced inflammation, cytokines secretion, DNA damage, and cell cycle arrest to lead to cellular senescence. Water chestnut shell (WCS) is a plant hull which containing polyphenolic compounds and showed antioxidant and anticancer activities. Orchid, which containing a natural polysaccharide compound, possesses many physiological activities including anti-inflammatory and neuroprotective effects. These agricultural plants might be able to reduce oxidative stress and inflammation. This study was used HG-induced human normal dermal fibroblasts (HG-HNDFs) as an in vitro model to disclose the effects of water extract of Phalaenopsis orchid flower (WEPF) and ethanol extract of water chestnut shell (EEWCS) on the anti-aging and their underlying molecular mechanisms. The toxicity of extracts on human normal dermal fibroblasts (HNDFs) was determined by MTT method. The senescence of cells was assayed by β-galactosidase (SA-β-gal) kit. ROS and nitrate production was analyzed by Intracellular ROS contents and ELISA, respectively. Western blotting was used to detect the proteins in cells. The results showed that the exposure of HNDFs to HG (30 mM) for 72 h were caused cellular senescence and arrested cells at G0/G1 phase. Indeed, the treatment of HG-HNDFs with WEPF (200 μg/ml) and EEWCS (10 μg/ml) significantly released cell cycle arrest and promoted cell proliferation. The G1/S phase transition regulatory proteins such as protein retinoblastoma (pRb), p53, and p16ᴵᴺᴷ⁴ᵃ depressed by WEPF and EEWCS were also observed. Additionally, the treatment of WEPF and EEWCS increased the activity of HO-1 through upregulating Nrf2 as well as decreased the ROS and NO of HG-HNDFs. Therefore, the senescence marker protein-30 (SMP30) in cells was diminished. In conclusion, the WEPF and EEWCS might inhibit HG-induced aging of HNDFs by reducing oxidative stress and free radicals.

Keywords: agricultural plant extract, anti-aging, high glucose, Phalaenopsis orchid flower, water chestnut shell

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Authors: Matheus Madureira Matos, Alexandre Rodrigues Farias

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Magnetic Resonance Imaging (MRI) is a vital imaging technique used in both clinical and pre-clinical areas to obtain detailed anatomical and functional information. However, MRI scans can be expensive, time-consuming, and often require the use of anesthetics to keep animals still during the imaging process. Anesthetics are commonly administered to animals undergoing MRI scans to ensure they remain still during the imaging process. However, prolonged or repeated exposure to anesthetics can have adverse effects on animals, including physiological alterations and potential toxicity. Minimizing the duration and frequency of anesthesia is, therefore, crucial for the well-being of research animals. In recent years, various sampling trajectories have been investigated to reduce the number of MRI measurements leading to shorter scanning time and minimizing the duration of animal exposure to the effects of anesthetics. Compressed sensing (CS) and sampling trajectories, such as cartesian, spiral, and radial, have emerged as powerful tools to reduce MRI data while preserving diagnostic quality. This work aims to apply CS and cartesian, spiral, and radial sampling trajectories for the reconstruction of MRI of the abdomen of mice sub-sampled at levels below that defined by the Nyquist theorem. The methodology of this work consists of using a fully sampled reference MRI of a female model C57B1/6 mouse acquired experimentally in a 4.7 Tesla MRI scanner for small animals using Spin Echo pulse sequences. The image is down-sampled by cartesian, radial, and spiral sampling paths and then reconstructed by CS. The quality of the reconstructed images is objectively assessed by three quality assessment techniques RMSE (Root mean square error), PSNR (Peak to Signal Noise Ratio), and SSIM (Structural similarity index measure). The utilization of optimized sampling trajectories and CS technique has demonstrated the potential for a significant reduction of up to 70% of image data acquisition. This result translates into shorter scan times, minimizing the duration and frequency of anesthesia administration and reducing the potential risks associated with it.

Keywords: compressed sensing, magnetic resonance, sampling trajectories, small animals

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Authors: Omoruyi G. Idemudia, Alexander P. Sadimenko

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The need for the development of new sustainable bioactive compounds with unique properties that can become potential replacement for commonly used medicinal drugs has continued to gain tremendous research concerns because of the problems of disease resistant to these medicinal drugs and their toxicity effects. NOS-donor heterocycles are particularly of interest as they have showed good pharmacological activities in the midst of their interesting chelating properties towards metal ions, an important characteristic for transition metal based drugs design. These new compounds have also gained application as dye sensitizers in solar cell panels for the generation of renewable solar energy, as greener water purification polymer for supply and management of clean water and as catalysts which are used to reduce the amount of pollutants from industrial reaction processes amongst others, because of their versatile properties. Di-ketone acylpyrazolones and their azomethine schiff bases have been employed as pharmaceuticals as well as analytical reagents, and their application as transition metal complexes have being well established. In this research work, a new 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one-thiosemicarbazone was synthesized from the reaction of 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one and thiosemicarbazide in methanol. The pure isolate of the thiosemicarbazone was further reacted with aqueous solutions of palladium and platinum salts to obtain their metal complexes, in an effort towards the discovery of transition metal based synthetic drugs. These compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one thiosemicarbazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group according to x-ray crystallography. The tridentate NOS ligand formed a tetrahedral geometry on coordinating with metal ions. Reported compounds showed varying antioxidant free radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 100, 200, 300, 400 and 500 µg/ml concentrations. The platinum complex have shown a very good antioxidant property against DPPH with an IC50 of 76.03 µg/ml compared with standard ascorbic acid (IC50 of 74.66 µg/ml) and as such have been identified as a potential anticancer candidate.

Keywords: acylpyrazolone, free radical scavenging activities, tridentate ligand, x-ray crystallography

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

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The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

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Authors: Satya P. Dubey, Hrushikesh A Abhyankar, Veronica Marchante, James L. Brighton, Björn Bergmann

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Aims: To develop a mathematical model that simulates the ROP of PLA taking into account the effect of alternative energy to be implemented in a continuous reactive extrusion production process of PLA. Introduction: The production of large amount of waste is one of the major challenges at the present time, and polymers represent 70% of global waste. PLA has emerged as a promising polymer as it is compostable, biodegradable thermoplastic polymer made from renewable sources. However, the main limitation for the application of PLA is the traces of toxic metal catalyst in the final product. Thus, a safe and efficient production process needs to be developed to avoid the potential hazards and toxicity. It has been found that alternative energy sources (LASER, ultrasounds, microwaves) could be a prominent option to facilitate the ROP of PLA via continuous reactive extrusion. This process may result in complete extraction of the metal catalysts and facilitate less active organic catalysts. Methodology: Initial investigation were performed using the data available in literature for the reaction mechanism of ROP of PLA based on conventional metal catalyst stannous octoate. A mathematical model has been developed by considering significant parameters such as different initial concentration ratio of catalyst, co-catalyst and impurity. Effects of temperature variation and alternative energies have been implemented in the model. Results: The validation of the mathematical model has been made by using data from literature as well as actual experiments. Validation of the model including alternative energies is in progress based on experimental data for partners of the InnoREX project consortium. Conclusion: The model developed reproduces accurately the polymerisation reaction when applying alternative energy. Alternative energies have a great positive effect to increase the conversion and molecular weight of the PLA. This model could be very useful tool to complement Ludovic® software to predict the large scale production process when using reactive extrusion.

Keywords: polymer, poly-lactic acid (PLA), ring opening polymerization (ROP), metal-catalyst, bio-degradable, renewable source, alternative energy (AE)

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Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: Luís R. Silva, Ana C. Gonçalves, Catarina Bento, Fábio Jesus, Branca M. Silva

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Prunus avium Linnaeus, more known as sweet cherry, is one of the most appreciated fruit worldwide. Most of these quantities are produced in Fundão region, being Saco the cultivar most produced. Saco is very rich in bioactive compounds, especially phenolics, and presents great antioxidant capacity. The purpose of the present study was to investigate the chemical profile and biological potential, concerning antioxidant, anti-diabetic activity and protective effects towards erythrocytes by Saco sweet cherry collected from Fundão region (Portugal). The hydroethanolic extracts were prepared and passed through a C18 solid-phase extraction column. The phenolic profile analyzed by LC-DAD method allowed to the identification of 22 phenolic compounds, being 16 non-phenolics and 6 anthocyanins. In respect to non-coloured phenolics, 3-O-caffeoylquinic and ρ-coumaroylquinic acids were the main ones. Concerning to anthocyanins, cyanidin-3-O-rutinoside was found in higher amounts. Relatively to biological potential, Saco showed great antioxidant potential, through DPPH and NO radical assays, with IC50 =16.24 ± 0.46 µg/mL and IC50 = 176.69 ± 3.35 µg/mL for DPPH and NO, respectively. These results were similar to those obtained for ascorbic acid control (IC50 = 16.92 ± 0.69 and IC50 = 162.66 ± 1.31 μg/mL for DPPH and NO, respectively). In respect to antidiabetic potential, Saco revealed capacity to inhibit α-glucosidase in a dose-dependent manner (IC50 = 10.79 ± 0.40 µg/mL), being much active than positive control acarbose (IC50 = 306.66 ± 0.84 μg/mL). Additionally, Saco extracts revealed protective effects against ROO•-mediated toxicity generated by AAPH in human blood erythrocytes, inhibiting hemoglobin oxidation (IC50 = 38.57 ± 0.96 μg/mL) and hemolysis (IC50 = 73.03 ± 1.48 μg/mL), in a concentration-dependent manner. However, Saco extracts were less effective than quercetin control (IC50 = 3.10 μg/mL and IC50 = 0.7 μg/mL for inhibition of hemoglobin oxidation and hemolysis, respectively). The results obtained showed that Saco is an excellent source of phenolic compounds. These ones are natural antioxidant substances, which easily capture reactive species. This work presents new insights regarding sweet cherry antioxidant properties which may be useful for the future development of new therapeutic strategies for preventing or attenuating oxidative-related disorders.

Keywords: antioxidant capacity, health benefits, phenolic compounds, saco

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.

Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle

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Authors: Marco Soto-Arriaza, Eduardo Cena-Ahumada, Jaime Melendez-Rojel

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Background: Liposomes have been widely used as a model of lipid bilayer to study the physicochemical properties of biological membrane, encapsulation, transport and release of different molecules. Furthermore, extensive research has focused on improving the efficiency in the transport of drugs, developing tools that improve the release of the encapsulated drug from liposomes. In this context, the enzymatic activity of PLA₂, despite having been shown to be an effective tool to promote the release of drugs from liposomes, is still an open field of research. Aim: The aim of the present study is to explore the effect of cholesterol (Cho) and amphipathic di- and tri-block copolymers, on calcein release mediated by enzymatic activity of PLA2 in Dipalmitoylphosphatidylcholine (DPPC) liposomes under physiological conditions. Methods: Different dispersions of DPPC, cholesterol, di-block POE₄₅-PCL₅₂ or tri-block PCL₁₂-POE₄₅-PCL₁₂ were prepared by the extrusion method after five freezing/thawing cycles; in Phosphate buffer 10mM pH 7.4 in presence of calcein. DPPC liposomes/Calcein were centrifuged at 15000rpm 10 min to separate free calcein. Enzymatic activity assays of PLA₂ were performed at 37°C using the TBS buffer pH 7.4. The size distribution, polydispersity, Z-potential and Calcein encapsulation of DPPC liposomes was monitored. Results: PLA₂ activity showed a slower kinetic of calcein release up to 20 mol% of cholesterol, evidencing a minimum at 10 mol% and then a maximum at 18 mol%. Regardless of the percentage of cholesterol, up to 18 mol% a one-hundred percentage release of calcein was observed. At higher cholesterol concentrations, PLA₂ showed to be inefficient or not to be involved in calcein release. In assays where copolymers were added in a concentration lower than their cmc, a similar behavior to those showed in the presence of Cho was observed, that is a slower kinetic in calcein release. In both experimental approaches, a one-hundred percentage of calcein release was observed. PLA₂ was shown to be sensitive to the 4-(4-Octadecylphenyl)-4-oxobutenoic acid inhibitor and calcium, reducing the release of calcein to 0%. Cell viability of HeLa cells decreased 7% in the presence of DPPC liposomes after 3 hours of incubation and 17% and 23% at 5 and 15 hours, respectively. Conclusion: Calcein release from DPPC liposomes, mediated by PLA₂ activity, depends on the percentage of cholesterol and the presence of copolymers. Both, cholesterol up to 20 mol% and copolymers below it cmc could be applied to the regulation of the kinetics of antitumoral drugs release without inducing cell toxicity per se.

Keywords: amphipathic copolymers, calcein release, cholesterol, DPPC liposome, phospholipase A₂

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Authors: Y. Sakai, C. Wang

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The decrease in agricultural production due to soil deterioration has been an urgent task. Soil acidification is a potentially serious land degradation issue and it will have a major impact on agricultural productivity and sustainable farming systems. In China, acid soil is mainly distributed in the southern part, the decrease in agricultural production and heavy metal contamination are serious problems. In addition, not only environmental and health problems due to the exhaust gas such as mainly sulfur dioxide (SO₂) but also the generation of a huge amount of construction and demolition wastes with the accelerating urbanization has emerged as a social problem in China. Therefore, the need for the recycling and reuse of both desulfurization waste and waste concrete is very urgent and necessary. So we have investigated the effectiveness as acid soil amendments of both coal bio-briquette ash and waste concrete. In this paper, acid soil (AS1) in Nanjing (pH=6.0, EC=1.6dSm-1) and acid soil (AS2) in Guangzhou (pH=4.1, EC=0.2dSm-1) were investigated in soil amelioration test. Soil amendments were three coal bio-briquette ashes (BBA1, BBA2 and BBA3), the waste cement fine powders (CFP) ( < 200µm (particle diameter)), waste concrete particles (WCP) ( < 4.75mm ( < 0.6mm, 0.6-1.0mm, 1.0-2.0mm, 2.0-4.75mm)), and six mixtures with two coal bio-briquette ashes (BBA2 and BBA3), CFP, WCP( < 0.6mm) and WCP(2.0-4.75mm). In acid soil amelioration test, the three BBAs, CFP and various WCPs based on exchangeable calcium concentration were added to two acid soils. The application rates were from 0 wt% to 3.5 wt% in AS1 test and from 0 wt% to 6.0 wt% in AS2 test, respectively. Soil chemical properties (pH, EC, exchangeable and soluble ions (Na, Ca, Mg, K)) before and after mixing with soil amendments were measured. In addition, Al toxicity and the balance of salts (CaO, K₂O, MgO) in soil after amelioration was evaluated. The order of pH and exchangeable Ca concentration that is effective for acid soil amelioration was WCP(0.6mm) > CFP > WCP(2.0-4.25mm) > BB1 > BB2 > BB3. In all AS 1 and AS 2 amelioration tests using three BBAs, the pH and EC increased slightly with the increase of application rate and reached to the appropriate value range of both pH and EC in BBA1 only. Because BBA1 was higher value in pH and exchangeable Ca. After that, soil pH and EC with the increase in the application rate of BBA2, BBA3 and by using CFP, WC( < 0.6mm), WC(2.0-4.75mm) as soil amendment reached to each appropriate value range, respectively. In addition, the mixture amendments with BBA2, BBA3 CFP, WC( < 0.6mm), and WC(2.0-4.75mm) could ameliorate at a smaller amount of application rate in case of BBA only. And the exchangeable Al concentration decreased drastically with the increase in pH due to soil amelioration and was under the standard value. Lastly, the heavy metal (Cd, As, Se, Ni, Cr, Pb, Mo, B, Cu, Zn) contents in new soil amendments were under control standard values for agricultural use in China. Thus we could propose a new acid soil amelioration method using coal bio-briquette ash and waste concrete in China.

Keywords: acid soil, coal bio-briquette ash, soil amelioration, waste concrete

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Authors: Nahal Najafi, Afsaneh Yegdaneh, Sedigheh Saberi

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Introduction: Leishmaniasis poses a substantial global risk, affecting millions and resulting in thousands of cases each year in endemic regions. Challenges in current leishmaniasis treatments include drug resistance, high toxicity, and pancreatitis. Marine compounds, particularly brown algae, serve as a valuable source of inspiration for discovering treatments against Leishmania. Material and method: Padina pavonica was collected from the Persian Gulf. The seaweeds were dried and extracted with methanol: ethylacetate (1:1). The extract was partitioned to hexane (Hex), dicholoromethane (DCM), butanol, and water by Kupchan partitioning method. Hex partition was fractionated by silica gel column chromatography to 10 fractions (Fr. 1-10). Fr. 6 was further separated by the normal phase HPLC method to yield compounds 1-3. The structures of isolated compounds were elucidated by NMR, Mass, and other spectroscopic methods. Hex and DCM partitions, Fr. 6 and compounds 1-3, were tested for anti-leishmanicidal activity. RAW cell lines were cultured in enriched RPMI (10% FBS, 1% pen-strep) in a 37°C CO2 5% incubator, while promastigote cells were initially cultured in NNN culture and subsequently transferred to the aforementioned medium. Cytotoxicity was assessed using MTT tests, anti-promastigote activity was evaluated through Hemocytometer chamber promastigote counting, and the impact of amastigote damage was determined by counting amastigotes within 100 macrophages. Results: NMR and Mass identified isolated compounds as fucosterol and two sulfoquinovosyldiacylglycerols (SQDG). Among the samples tested, Fr.6 exhibited the highest cytotoxicity (CC50=60.24), while compound 2 showed the lowest cytotoxicity (CC50=21984). Compound 1 and dichloromethane fraction demonstrated the highest and lowest anti-promastigote activity (IC50=115.7, IC50=16.42, respectively), and compound 1 and hexane fraction exhibited the highest and lowest anti-amastigote activity (IC50=7.874, IC50=40.18, respectively). Conclusion: All six samples, including Hex and DCM partitions, Fr.6, and compounds 1-3, demonstrate a noteworthy correlation between rising concentration and time, with a statistically significant P-value of ≤0.05. Considering the higher selectivity index of compound 2 compared to others, it can be inferred that the presence of sulfur groups and unsaturated chains potentially contributes to these effects by impeding the DNA polymerase, which, of course, needs more research.

Keywords: Padina, leishmania, sulfoquinovosyldiacylglycerol, cytotoxicity

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

Abstract:

Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

Procedia PDF Downloads 259

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

Abstract:

Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

Procedia PDF Downloads 128