Search results for: inhibition of cancer cells

Authors: P. Haldar, P. Ghosh, S. Ghoshdastidar, K. Kargupta

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In polymer electrolyte membrane fuel cells (PEMFC), the membrane electrode assembly (MEA) is consisting of two platinum coated carbon electrodes, sandwiched with one proton conducting phosphoric acid doped polymeric membrane. Due to low mechanical stability, flooding and fuel cell crossover, application of phosphoric acid in polymeric membrane is very critical. Phosphorous and silica based 3D inorganic gel gains the attention in the field of supercapacitors, fuel cells and metal hydrate batteries due to its thermally stable highly proton conductive behavior. Also as a large amount of water molecule and phosphoric acid can easily get trapped in Si-O-Si network cavities, it causes a prevention in the leaching out. In this study, we have performed molecular dynamics (MD) simulation and first principle calculations to understand the structural, electronics and electrochemical and morphological behavior of this inorganic gel at various P to Si ratios. We have used dipole-dipole interactions, H bonding, and van der Waals forces to study the main interactions between the molecules. A 'structure property-performance' mapping is initiated to determine optimum P to Si ratio for best proton conductivity. We have performed the MD simulations at various temperature to understand the temperature dependency on proton conductivity. The observed results will propose a model which fits well with experimental data and other literature values. We have also studied the mechanism behind proton conductivity. And finally we have proposed a structure for the gel paste with optimum P to Si ratio.

Keywords: first principle calculation, molecular dynamics simulation, phosphorous and silica based 3D inorganic gel, polymer electrolyte membrane fuel cells, proton conductivity

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Authors: Thomas Heffernan, Nick Neave, Colin Hamilton, Gill Case

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Hoarding is the acquisition of and failure to discard possessions, leading to excessive clutter and significant psychological/emotional distress. From a cognitive-behavioural approach, excessive hoarding arises from information-processing deficits, as well as from problems with emotional attachment to possessions and beliefs about the nature of possessions. In terms of information processing, hoarders have shown deficits in executive functions, including working memory, planning, inhibitory control, and cognitive flexibility. However, this previous research is often confounded by co-morbid factors such as anxiety, depression, or obsessive-compulsive disorder. The current study adopted a cognitive-behavioural approach, specifically assessing executive deficits and working memory in a non-clinical sample of hoarders, compared with non-hoarders. In this study, a non-clinical sample of 40 hoarders and 73 non-hoarders (defined by The Savings Inventory-Revised) completed the Adult Executive Functioning Inventory, which measures working memory and inhibition, Dysexecutive Questionnaire-Revised, which measures general executive function and the Hospital Anxiety and Depression Scale, which measures mood. The participant sample was made up of unpaid young adult volunteers who were undergraduate students and who completed the questionnaires on a university campus. The results revealed that, after observing no differences between hoarders and non-hoarders on age, sex, and mood, hoarders reported significantly more deficits in inhibitory control and general executive function when compared with non-hoarders. There was no between-group difference on general working memory. This suggests that non-clinical hoarders have a specific difficulty with inhibition-control, which enables you to resist repeated, unwanted urges. This might explain the hoarder’s inability to resist urges to buy and keep items that are no longer of any practical use. These deficits may be underpinned by general executive function deficiencies.

Keywords: hoarding, memory, executive, deficits

Procedia PDF Downloads 188

Authors: Alexandra Tucaliuc, Alexandra C. Blaga, Anca I. Galaction, Lenuta Kloetzer, Dan Cascaval

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Ergosterol (ergosta-5,7,22-trien-3β-ol), also known as provitamin D2, is the precursor of vitamin D2 (ergocalciferol), because it is converted under UV radiation to this vitamin. The natural sources of ergosterol are mainly the yeasts (Saccharomyces sp., Candida sp.), but it can be also found in fungus (Claviceps sp.) or plants (orchids). In the yeasts cells, ergosterol is accumulated in membranes, especially in free form in the plasma membrane, but also as esters with fatty acids in membrane lipids. The chemical synthesis of ergosterol does not represent an efficient method for its production, in these circumstances, the most attractive alternative for producing ergosterol at larger-scale remains the aerobic fermentation using S. cerevisiae on glucose or by-products from agriculture of food industry as substrates, in batch or fed-batch operating systems. The aim of this work is to analyze comparatively the influence of aeration efficiency on ergosterol production by S. cerevisiae in batch and fed-batch fermentations, by considering different levels of mixing intensity, aeration rate, and n-dodecane concentration. The effects of the studied factors are quantitatively described by means of the mathematical correlations proposed for each of the two fermentation systems, valid both for the absence and presence of oxygen-vector inside the broth. The experiments were carried out in a laboratory stirred bioreactor, provided with computer-controlled and recorded parameters. n-Dodecane was used as oxygen-vector and the ergosterol content inside the yeasts cells has been considered at the fermentation moment related to the maximum concentration of ergosterol, 9 hrs for batch process and 20 hrs for fed-batch one. Ergosterol biosynthesis is strongly dependent on the dissolved oxygen concentration. The hydrocarbon concentration exhibits a significant influence on ergosterol production mainly by accelerating the oxygen transfer rate. Regardless of n-dodecane addition, by maintaining the glucose concentration at a constant level in the fed-batch process, the amount of ergosterol accumulated into the yeasts cells has been almost tripled. In the presence of hydrocarbon, the ergosterol concentration increased by over 50%. The value of oxygen-vector concentration corresponding to the maximum level of ergosterol depends mainly on biomass concentration, due to its negative influences on broth viscosity and interfacial phenomena of air bubbles blockage through the adsorption of hydrocarbon droplets–yeast cells associations. Therefore, for the batch process, the maximum ergosterol amount was reached for 5% vol. n-dodecane, while for the fed-batch process for 10% vol. hydrocarbon.

Keywords: bioreactors, ergosterol, fermentation, oxygen-vector

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Authors: Van Tang Nguyen, Jennette A. Sakoff, Christopher J. Scarlett

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Phyllanthus amarus (P. amarus) has been used as a traditional herbal plant for the treatment of chronic ailments such as hepatitis, diabetes and cancer. The objectives of this study were to determine the physicochemical properties, antioxidant and cytotoxic activities of crude P. amarus extracts and fractions using MTT and CCK-8 assays for cytotoxic evaluation. The outcomes indicated that P. amarus methanol (PAM) extract had lower residual moisture (7.40%) and water activity (0.24) and higher contents of saponins, phenolics, flavonoids and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents/g dried extract, respectively) than those of P. amarus water (PAW) extract, resulting antioxidant activity of PAM extract was significantly higher (P < 0.05) than that of PAW extract, PAM fractions and phyllanthin (a major compound in P. amarus). Cytotoxic activity of PAM extract for cancer cell lines of MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was higher than those of PAW extract and PAM fractions. Therefore, we can conclude that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs.

Keywords: antioxidant, cytotoxicity, Phyllanthus amarus, physicochemical

Procedia PDF Downloads 318

Authors: Gema Gómez-Casado, Alba Rodríguez-Muñoz, Virginia Mela-Rivas, Pallavi Kompella, Francisco José Tinahones-Madueña, Isabel Moreno-Indias, Almudena Ortega-Gómez

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Obesity is a high-priority health problem worldwide due to its high prevalence. The proportion of obese and overweight subjects in industrialized countries exceeds half of the population in most cases. Beyond the metabolic problem, obesity boosts inflammation levels in the organism. The gut microbiota, considered an organ by itself, controls a high variety of processes at a systemic level. In fact, the microbiota interacts closely with the immune system, being crucial in determining the maturation state of neutrophils, key effectors of the innate immune response. It is known that changes in the diet exert strong effects on the variety and activity of the gut microbiota. The effect that those changes have on the axis microbiota-immune response is an unexplored field. In this study, 10 patients with obesity (weight 114,3 ± 14,5Kg, BMI 40,47±3,66) followed a Mediterranean-hypocaloric diet for 3 months, reducing their initial weight by 12,71 ± 3%. A transplant of microbiota from these patients before and after the diet was performed into wild type “germ-free” mice (n=10/group), treated with antibiotics. Six weeks after the transplant, mice were euthanized, and the presence of cells from the innate immune system were analysed in different organs (bone marrow, blood, spleen, visceral adipose tissue, and intestine) by flow cytometry. No differences were observed in the number of myeloid cells in bone marrow, blood, spleen, or visceral adipose tissue of mice transplanted with patient’s microbiota before and after following the Mediterranean diet. However, the intestine of mice that received post-diet microbiota presented a marked decrease in the number of neutrophils (whose presence is associated with tissue inflammation), as well as macrophages. In line with these findings, intestine monocytes from mice with post-diet microbiota showed a less inflammatory profile (lower Ly6Gˡᵒʷ proportion of cells). These results point toward a decrease in the inflammatory state of the intestinal tissue, derived from changes in the gut microbiota, which occurred after a 3-month Mediterranean diet.

Keywords: obesity, nutrition, Mediterranean diet, gut microbiota, immune system

Procedia PDF Downloads 118

Authors: Ali A. Bazzi, Ameer Hamza, Riley O’Hara, Kimberly Kado, Karen H. Hagglund, Lamia Fathallah, Robert T. Morris

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Introduction: Endometrial Cancer is a common gynecologic malignancy primarily treated with complete surgical staging, which may include complete pelvic and para-aortic lymphadenectomy. The role of lymphadenectomy is controversial, especially the intraoperative indications for the procedure. Three factors are important in decision to proceed with lymphadenectomy: Myometrial invasion, maximum tumor dimension, and histology. Many institutions incorporate these criteria in varying degrees in the decision to proceed with lymphadenectomy. This investigation assesses the use of intraoperatively measured MTD with and without pre-operative histologic grade. Methods: This study compared retrospectively EEC patients with intraoperatively measured MTD ≤2 cm to those with MTD >2 cm from January 1, 2002 to August 31, 2017. This assessment compared those with MTD ≤ 2cm with endometrial biopsy (EB) grade 1-2 to patients with MTD > 2cm with EB grade 3. Lymph node metastasis (LNM), recurrence, and survival were compared in these groups. Results: This study reviewed 222 patient cases. In tumors > 2 cm, LNM occurred in 20% cases while in tumors ≤ 2 cm, LNM was found in 6% cases (p=0.04). Recurrence and mean survival based on last follow up visit in these two groups were not statistically different (p=0.78 and 0.36 respectively). Data demonstrated a trend that when combined with preoperative EB International Federation of Gynecology and Obstetrics (FIGO) grade, a higher proportion of patients with EB FIGO Grade 3 and MTD > 2 cm had LNM compared to those with EB FIGO Grade 1-2 and MTD ≤ 2 cm (43% vs, 11%, p=0.06). LNM was found in 15% of cases in which lymphadenectomy was performed based on current practices, whereas if the criteria of EB FIGO 3 and MTD > 2 cm were used the incidence of LNM would have been 44% cases. However, using this criterion, two patients would not have had their nodal metastases detected. Compared to the current practice, the sensitivity and specificity of the proposed criteria would be 60% and 81%, respectively. The PPV and NPV would be 43% and 90%, respectively. Conclusion: The results indicate that MTD combined with EB FIGO grade can detect LNM in a higher proportion of cases when compared to current practice. MTD combined with EB FIGO grade may eliminate the need of frozen section sampling in a substantial number of cases.

Keywords: endometrial cancer, FIGO grade, lymphadenectomy, tumor size

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Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

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Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

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Authors: Suttijit Sriwatcharakul

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The bioactivity studies from the weed ethanolic crude extracts from leaf, stem, pod and root of wild spider flower; Cleoma viscosa Linn. were analyzed for the growth inhibition of 6 bacterial species; Salmonella typhimurium TISTR 5562, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus TISTR 1466, Streptococcus epidermidis ATCC 1228, Escherichia coli DMST 4212 and Bacillus subtilis ATCC 6633 with initial concentration crude extract of 50 mg/ml. The agar well diffusion results found that the extracts inhibit only gram positive bacteria species; S. aureus, S. epidermidis and B. subtilis. The minimum inhibition concentration study with gram positive strains revealed that leaf crude extract give the best result of the lowest concentration compared with other plant parts to inhibit the growth of S. aureus, S. epidermidis and B. subtilis at 0.78, 0.39 and lower than 0.39 mg/ml, respectively. The determination of total phenolic compounds in the crude extracts exhibited the highest phenolic content was 10.41 mg GAE/g dry weight in leaf crude extract. Analyzed the efficacy of free radical scavenging by using DPPH radical scavenging assay with all crude extracts showed value of IC50 of leaf, stem, pod and root crude extracts were 8.32, 12.26, 21.62 and 35.99 mg/ml, respectively. Studied cytotoxicity of crude extracts on human breast adenocarcinoma cell line by MTT assay found that pod extract had the most cytotoxicity CC50 value, 32.41 µg/ml. Antioxidant activity and cytotoxicity of crude extracts exhibited that the more increase of extract concentration, the more activities indicated. According to the bioactivities results, the leaf crude extract of Cleoma viscosa Linn. is the most interesting plant part for further work to search the beneficial of this weed.

Keywords: antimicrobial, antioxidant activity, Cleoma viscosa Linn., cytotoxicity test, total phenolic compound

Procedia PDF Downloads 265

Authors: Pei-Shan Liang

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Objective: This article explores the care experience of a terminal lung cancer patient who developed lower limb paralysis after surgery for aortic dissection. The patient, diagnosed with aortic dissection during chemotherapy for lung cancer, faced post-surgical lower limb paralysis, leading to feelings of helplessness and hopelessness as they approached death with reduced mobility. Methods: The nursing period was from July 19 to July 27, during which the author, alongside the intensive care team and palliative care specialists, conducted a comprehensive assessment through observation, direct care, conversations, physical assessments, and medical record review. Gordon's eleven functional health patterns were used for a holistic evaluation, identifying four nursing health issues: "pain related to terminal lung cancer and invasive procedures," "decreased cardiac tissue perfusion due to hemodynamic instability," "impaired physical mobility related to lower limb paralysis," and "hopelessness due to the unpredictable prognosis of terminal lung cancer." Results: The medical team initially focused on symptom relief, administering Morphine 5mg in 0.9% N/S 50ml IVD q6h for pain management and continuing chemotherapy as prescribed. Open communication was employed to address the patient's physical, psychological, and spiritual concerns. Non-pharmacological interventions, including listening, caring, companionship, opioid medication, and distraction techniques like comfortable positioning and warm foot baths, were used to alleviate pain, reducing the pain score to 3 on the numeric rating scale and easing respiratory discomfort. The palliative care team was also involved, guiding the patient and family through the "Four Paths of Life," helping the patient achieve a good end-of-life experience and the family to experience a peaceful life. This process also served to promote the concept of palliative care, enabling more patients and families to receive high-quality and dignified care. The patient was encouraged to express inner anxiety through drawing or writing, which helped reduce the hopelessness caused by psychological distress and uncertainty about the disease's prognosis, as assessed by the Hospital Anxiety and Depression Scale, reaching a level of mild anxiety but acceptable without affecting sleep. Conclusion: What left a deep impression during the care process was the need for intensive care providers to consider the patient's psychological state, not just their physical condition, when the patient's situation changes. Family support and involvement often provide the greatest solace for the patient, emphasizing the importance of comfort and dignity. This includes oral care to maintain cleanliness and comfort, frequent repositioning to alleviate pressure and discomfort, and timely removal of invasive devices and unnecessary medications to avoid unnecessary suffering. The nursing process should also address the patient's psychological needs, offering comfort and support to ensure that they can face the end of life with peace and dignity.

Keywords: intensive care, lung cancer, aortic dissection, lower limb paralysis

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Authors: Vidia A. Nuraini, Eugene M. H. Yee, Mohan Bhadbhade, David StC. Black, Naresh Kumar

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Flavonoids are naturally occurring compounds that have been shown to exhibit a wide range of biological properties including anticancer and anti-inflammatory activities. However, flavonoids suffer from low bioavailability, which limits their overall utility for therapeutic applications. One of the methods to overcome this limitation is through structural modification of natural flavonoids. In this study, flavanone, isoflavanone, and isoflavene, were structurally modified through the introduction of additional fused-ring systems via ortho-quinone methide intermediates (o-QMs). These intermediates can readily undergo a [4+2] cycloaddition through an inverse-electron-demand Diels–Alder reaction with electron-rich dienophiles. A regioselective Mannich reaction using bis-(N,N-dimethylamino)methane was employed to generate the o-QM precursors of flavanone, isoflavanone, and isoflavene. The o-QM intermediates were subsequently generated in situ through thermal elimination of the dimethylamine functionality and reacted with a variety of dienophiles to produce novel flavonoids with fused-ring systems. A total of 21 novel flavonoid analogs were successfully synthesized. The X-ray crystal structure of cycloaddition adducts, particularly those derived from 3,4-dihydro-2H-pyran and p-methoxystyrene revealed a special case of enantiomeric disorder, where two enantiomers in equal amounts superpose with one another, with the exception for atoms that have opposite configuration. The anticancer properties of fused-ring systems derived from isoflavene were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. One of these cycloaddition adducts had displayed improved anti-proliferative activity against MDA-MB-231 and U87 cancer cell lines as compared to the parent compound. Further anticancer and anti-inflammatory activities of the flavanone and isoflavanone analogs are currently being investigated.

Keywords: Diels-Alder reaction, flavonoids, Mannich reaction, ortho-quinone methide.

Procedia PDF Downloads 243

Authors: Abir Mohamed Mohamed Ibrahim, Amina Titouche, Mohamed Hazzit

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Phytotherapy is based on use of plant natural products holding the main sources of drugs with healing properties for the treatment of human, animal or vegetable diseases. With these aims, and to replace chemical preservatives in natural products, we are interested to use essential oils from Algerian endemic plants belonging to the Asteraceae family: Artemisia herba alba Asso, which was undergoes a hydro-distillation after its irradiation by Gamma rays at frequencies: 10, 20, and 30 KGray which gave respectively the following essential oil yields: 1.087%, 1.087%, 1.085%, compared with that of the untreated sample giving a yield of 1.27 %. Evaluation of the antioxidant activity in vitro of essential oil for A. herba alba has been assessed by two different methods: inhibition of DPPH radical and measurement of reducing power. The first method has not revealed a very big difference regardless of the dose of irradiation, the IC50 is about 4000 mg/l, the maximum of inhibition was around 49.4%, likewise, the test of reducing power awarded us a maximum reducing capacity was of 0.76%; both of results were registered by the specimen irradiated at 20 KGy, it has a more better antioxidant power than no irradiated sample but slightly. To combat Fusarium culmorum, causing the wilts and rots, we are focused on the antifungal screening of this aromatic plant. The results obtained, followed by measurements of Minimal Inhibitory Concentrations (MIC); showed promising inhibitory effect against pathogen tested. With a yield superior to l%, the essential oil has shown a remarkable efficiency on the stump, mainly for sample irradiate at 30KGray (MICs= 625 µg/ml; MICc= 1250 µg/ml) with MIC of 2%. These results demonstrate a good antifungal activity, to limit and even to stop the development of the pathogenic microorganism and also the positive effect of dose of irradiation to upgrade this capacity as well, to uphold the antioxidant capacity.

Keywords: artemisia herba alba Asso, essential oil yield, gamma ray, antioxidant activity, antifungal activity

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Authors: Layaly Ayoub, Mariana Ribeiro

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Introduction: Breast cancer is currently considered the leading cause of cancer-related deaths among women in Brazil. Mastectomy, essential in this treatment, often necessitates subsequent breast reconstruction to restore physical appearance and aid in the emotional and psychological recovery of patients. The choice between immediate or delayed reconstruction is influenced by factors such as the type and stage of cancer, as well as the patient's overall health. The decision between autologous breast reconstruction or implant-based reconstruction requires a detailed analysis of individual conditions and needs. Objectives: This study analyzes the techniques and indications used in post-mastectomy breast reconstruction. Methodology: Literature review conducted in the PubMed and SciELO databases, focusing on articles that met the inclusion and exclusion criteria and descriptors. Results: After mastectomy, breast reconstruction is commonly performed. It is necessary to determine the type of technique to be used in each case depending on the specific characteristics of each patient. The tissue expander technique is indicated for patients with sufficient skin and tissue post-mastectomy, who do not require additional radiotherapy, and who opt for a less complex surgery with a shorter recovery time. This procedure promotes the gradual expansion of soft tissues where the definitive implant will be placed. Both temporary and permanent expanders offer flexibility, allowing for adjustment in the expander size until the desired volume is reached, enabling the skin and tissues to adapt to the breast implant area. Conversely, autologous reconstruction is indicated for patients who will undergo radiotherapy, have insufficient tissue, and prefer a more natural solution. This technique uses the transverse rectus abdominis muscle (TRAM) flap, the latissimus dorsi muscle flap, the gluteal flap, and local muscle flaps to shape a new breast, potentially combined with a breast implant. Conclusion: In this context, it is essential to conduct a thorough evaluation regarding the technique to be applied, as both have their benefits and challenges.

Keywords: indications, post-mastectomy, breast reconstruction, techniques

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Authors: Georgia Saxami, Evangelia N. Kerezoudi, Evdokia K. Mitsou, Marigoula Vlassopoulou, Georgios Zervakis, Adamantini Kyriacou

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Autism Spectrum Disorder (ASD) is a complex group of developmental disorders of the brain, characterized by social and communication dysfunctions, stereotypes and repetitive behaviors. The potential interaction between gut microbiota (GM) and autism has not been fully elucidated. Children with autism often suffer gastrointestinal dysfunctions, while alterations or dysbiosis of GM have also been observed. Treatment with dietary components has been postulated to regulate GM and improve gastrointestinal symptoms, but there is a lack of evidence for such approaches in autism, especially for prebiotics. This study assessed the effects of Pleurotus eryngii mushroom (candidate prebiotic) and inulin (known prebiotic compound) on gut microbial composition, using faecal samples from autistic children in an in vitro batch culture fermentation system. Selected members of GM were enumerated at baseline (0 h) and after 24 h fermentation by quantitative PCR. After 24 h fermentation, inulin and P. eryngii mushroom induced a significant increase in total bacteria and Faecalibacterium prausnitzii compared to the negative control (gut microbiota of each autistic donor with no carbohydrate source), whereas both treatments induced a significant increase in levels of total bacteria, Bifidobacterium spp. and Prevotella spp. compared to baseline (t=0h) (p for all <0.05). Furthermore, this study evaluated the impact of fermentation supernatants (FSs), derived from P. eryngii mushroom or inulin, on the expression levels of tight junctions’ genes (zonulin-1, occludin and claudin-1) in Caco-2 cells stimulated by bacterial lipopolysaccharides (LPS). Pre-incubation of Caco-2 cells with FS from P. eryngii mushroom led to a significant increase in the expression levels of zonulin-1, occludin and claudin-1 genes compared to the untreated cells, the cells that were subjected to LPS and the cells that were challenged with FS from negative control (p for all <0.05). In addition, incubation with FS from P. eryngii mushroom led to the highest mean expression values for zonulin-1 and claudin-1 genes, which differed significantly compared to inulin (p for all <0.05). Overall, this research highlighted the beneficial in vitro effects of P. eryngii mushroom on the composition of GM of autistic children after 24 h of fermentation. Also, our data highlighted the potential preventive effect of P. eryngii FSs against dysregulation of the intestinal barrier, through upregulation of tight junctions’ genes associated with the integrity and function of the intestinal barrier. This research has been financed by "Supporting Researchers with Emphasis on Young Researchers - Round B", Operational Program "Human Resource Development, Education and Lifelong Learning."

Keywords: gut microbiota, intestinal barrier, autism spectrum disorders, Pleurotus Eryngii

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Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

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The digestive system of insects is composed of three distinct regions: fore-, mid- and hingut. The middle region (the midgut) is treated as one of the barriers which protects the organism against any stressors which originate from external environment, e.g. toxic metals. Such factors can activate the cell death in epithelial cells to preserve the entire tissue/organs against the degeneration. Different mechanisms involved in homeostasis maintenance have been described, but the studies of animals under field conditions do not give the opportunity to conclude about potential ability of subsequent generation to inherit the tolerance mechanisms. It is possible only by a multigenerational strain of an animal led under laboratory conditions, exposed to a selected toxic factor, present also in polluted ecosystems. The main purpose of the project was to check if changes, which appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects with the special emphasis on apoptosis. As the animal for these studies we chose 5th larval stage of the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), which is one of pest of many vegetable crops. Animals were divided into some experimental groups: K, Cd, KCd, Cd1, Cd2, Cd3. A control group (K) fed a standard diet, and was conducted for XX generations, a cadmium group (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for XXX generations. A reference Cd group (KCd) has been initiated: control insects were fed with Cd supplemented diet (44 mg Cd per kg of dry weight of food). Experimental groups Cd1, Cd2, Cd3 developed from the control one: 5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food. We were interested in the activation of apoptosis during following generations in all experimental groups. Therefore, during the 1st year of the experiment, the measurements were done for 6 generations in all experimental group. The intensity and the course of apoptosis have been examined using transmission electron microscope (TEM), confocal microscope and flow cytometry. During apoptosis the cell started to shrink, extracellular spaces appeared between digestive and neighboring cells, the nucleus achieved a lobular shape. Eventually, the apoptotic cells was discharged into the midgut lumen. A quantitative analysis revealed that the number of apoptotic cells depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the following 6 generations, we observed that the percentage of apoptotic cells in the midguts from cadmium-exposed groups decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. At the same time, it was still higher than the percentage of apoptotic cells in the same tissues of the insects from the control and multigenerational cadmium strain. The results of our studies suggest that changes caused by cadmium treatment were preserved during 6-generational development of lepidopteran larvae. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: cadmium, cell death, digestive system, ultrastructure

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Authors: Ali Bayram, Burak Uz, Remzi Yiğiter

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The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.

Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

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Authors: Farzad Doostishoar, Abdolreza Hasanzadeh, Seyed Amin Ayatolahi Mousavi

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Introduction and Goals: Deuterium has different action from its isotopes hydrogen in chemical reactions and biochemical processes. It is not a significant difference in heavier atoms between the behavior of heavier isotope and the lighter One but for very lighter atoms it is significant . According to that most of the weight of all creatures body is water natural rate can be significant. In this article we want to study the effect of reduced deuterium on the fungus cell. If we saw the dependence of deuterium concentration of environment on the cells growth we can test this in invivo models too. Methods: First we measured deuterium concentration of the distillated water this analyze was operated by Arak’s heavy water company. Then the deuterium was diluted to ½ ¼ 1/8 1/16 by adding water free of deuterium for making media. In tree of samples the deuterium concentration was increased by adding D2O up to 10,50,100 times more concentrated. For candida albicans growth we used sabor medium and for aspergillus fomigatis growth we used sabor medium containing chloramphenicol. After culturing the funguses species we put the mediums for each species in the shaker incubator for 10 days in 25 centigrade. In different days and times the plates were studied morphologically and some microscopic characteristics were studied too. This experiments and cultures were repeated 3 times. Results: Statistical analyzes by paired-sample T test showed that aspergilus fomigatoos growth was decreased in concentration of 72 ppm( half deuterium concentration of negative control) significantly. In deuterium concentration reduction the growth reduce into the negative control significantly. The project results showed that candida albicans was sensitive to reduce and decrease of the deuterium in all concentrations.

Keywords: deuterium, cancer cell, growth, candida albicans

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Authors: Annisa Ulfah Pristya, Andi Setiawan

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Electricity is the primary requirement today's world, including Indonesia. This is because electricity is a source of electrical energy that is flexible to use. Fossil energy sources are the major energy source that is used as a source of energy power plants. Unfortunately, this conversion process impacts on the depletion of fossil fuel reserves and causes an increase in the amount of CO2 in the atmosphere, disrupting health, ozone depletion, and the greenhouse effect. Solutions have been applied are solar cells, ocean wave power, the wind, water, and so forth. However, low efficiency and complicated treatment led to most people and industry in Indonesia still using fossil fuels. Referring to this Fuel Cell was developed. Fuel Cells are electrochemical technology that continuously converts chemical energy into electrical energy for the fuel and oxidizer are the efficiency is considerably higher than the previous natural source of electrical energy, which is 40-60%. However, Fuel Cells still have some weaknesses in terms of the use of an expensive platinum catalyst which is limited and not environmentally friendly. Because of it, required the simultaneous source of electrical energy and environmentally friendly. On the other hand, Indonesia is a rich country in marine sediments and organic content that is never exhausted. Stacking the organic component can be an alternative energy source continued development of fuel cell is A Microbial Fuel Cell. Microbial Fuel Cells (MFC) is a tool that uses bacteria to generate electricity from organic and non-organic compounds. MFC same tools as usual fuel cell composed of an anode, cathode and electrolyte. Its main advantage is the catalyst in the microbial fuel cell is a microorganism and working conditions carried out in neutral solution, low temperatures, and environmentally friendly than previous fuel cells (Chemistry Fuel Cell). However, when compared to Chemistry Fuel Cell, MFC only have an efficiency of 40%. Therefore, the authors provide a solution in the form of Nano-MFC (Nano Microbial Fuel Cell): Utilization of Carbon Nano Tube to Increase Efficiency of Microbial Fuel Cell Power as an Effective, Efficient and Environmentally Friendly Alternative Energy Source. Nano-MFC has the advantage of an effective, high efficiency, cheap and environmental friendly. Related stakeholders that helped are government ministers, especially Energy Minister, the Institute for Research, as well as the industry as a production executive facilitator. strategic steps undertaken to achieve that begin from conduct preliminary research, then lab scale testing, and dissemination and build cooperation with related parties (MOU), conduct last research and its applications in the field, then do the licensing and production of Nano-MFC on an industrial scale and publications to the public.

Keywords: CNT, efficiency, electric, microorganisms, sediment

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Tahra ElObeid, Omnya Ahmed, Reem Al-Sharshani, Doaa Dalloul, Jannat Alnattei

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Background: Camelus dormedarius camels are also called ‘the Arabian camels’ and are present in the desert area of North Africa and the Middle East. Recently, camel’s milk has a great attention globally because of their proteins and peptides that have been reported to be beneficial for the health and in the management of many diseases. Objectives: This study was designed to investigate the antioxidant, antimicrobial activity and to evaluate the total phenolic content of camel’s milk proteins in Qatar. Methods: Fresh two camel’s milk samples from Omani breed and called Muhajer (camel’s milk A and B) were collected on the 1st of the December. Both samples were from the same location Al- Shahaniyah, Doha, Qatar, but from different local private farms and feeding system. Camel’s milk A and B were defatted by centrifugation and their proteins were extracted by acid and thermal precipitation. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Total phenolic compound (TPC) was evaluated by Folin-Ciocalteu reagent (FCR). On the other hand, the antimicrobial activity against eight different type of pathogenic bacteria was evaluated by disc diffusion method and the zone of inhibition was measured. Results: The of the total phenolic content of whole milk in both camel’s milk A and B were significantly the highest among the protein extracts. The % of the DPPH radical inhibition of casein protein in both camel’s milk A and B were significantly the highest among the protein extracts. In this study, there were marked changes in the antibacterial activity in the different camel milk protein extracts. All extracts showed bacterial overgrowth. Conclusion: The antioxidant activity of the camel milk protein extracts correlated to their unique phenolic compounds and bioactive protein peptides. The antimicrobial activity was not detected perhaps due to the technique, the quality, or the extraction method. Overall, camel's milk exhibits a high antioxidant activity, which is responsible for many health benefits besides the nutritional values.

Keywords: camels milk, antioxidant content, antimicrobial activity, proteins, Qatar

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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Postmenopausal osteoporosis is characterized by low bone density which leads to increased bone fragility and greater susceptibility to fracture. Current treatments for osteoporosis are dominated by drugs that inhibit bone resorption although they also suppress bone formation that may contribute to pathogenesis of osteonecrosis. To restore the extensive bone loss, there is a great need for anabolic treatments that induce osteoblasts to build new bone. Pre-osteoblastic cells produce proteins of the extra-cellular matrix, including type I collagen at first, and then to successively produce alkaline phosphatase (ALP) and osteocalcin during differentiation to osteoblasts. Finally, osteoblasts deposit calcium. Present study investigated the effects of egg yolk peptide (EYP) on osteogenic activities and bone matrix gene expressions in human osteoblastic MG-63 cells. The effects of EYP on cell proliferation, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization were measured. The expression of osteogenic genes including COL1A1 (collagen, type I, alpha 1), ALP, BGLAP (osteocalcin), and SPP1 (secreted phosphoprotein 1, osteopontin) were measured by quantitative realtime PCR. EYP dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. Furthermore, COL1A1, ALP, and SPP1 gene expressions were increased by EYP treatment. Present study suggested that EYP treatment enhanced osteogenic activities and increased bone matrix osteogenicgenes. These results could provide a mechanistic explanation for the bone-strengthening effects of EYP.

Keywords: egg yolk peptide, osteoblastic MG-63 cells, alkaline phosphatase, collagen synthesis, osteogenic genes, COL1A1, osteocalcin, osteopontin

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Authors: Kyoung Lee

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Numerous aerobic bacteria have the ability to form multicellular communities on the surface layer of the air-liquid (A-L) interface as a biofilm called a pellicle. Pellicles occupied at the A-L interface will benefit from the utilization of oxygen from air and nutrient from liquid. Buoyancy of cells can be obtained by high surface tension at the A-L interface. Thus, formation of pellicles is an adaptive advantage in utilization of excess nutrients in the standing culture where oxygen depletion is easily set up due to rapid cell growth. In natural environments, pellicles are commonly observed on the surface of lake or pond contaminated with pollutants. Previously, we have shown that when cultured in standing LB media an alkylphenol-degrading bacteria Pseudomonas alkylphenolia KL28 forms pellicles in a diameter of 0.3-0.5 mm with a thickness of ca 40 µm. The pellicles have unique features for possessing flatness and unusual rigidity. In this study, the biogenesis of the circular pellicles has been investigated by observing the cell organization at early stages of pellicle formation and cell arrangements in pellicle, providing a clue for highly organized cellular arrangement to be adapted to the air-liquid niche. Here, we first monitored developmental patterns of pellicle from monolayer to multicellular organization. Pellicles were shaped by controlled growth of constituent cells which accumulate extracellular polymeric substance. The initial two-dimensional growth was transited to multilayers by a constraint force of accumulated self-produced extracellular polymeric substance. Experiments showed that pellicles are formed by clonal growth and even with knock-out of genes for flagella and pilus formation. In contrast, the mutants in the epm gene cluster for alginate-like polymer biosynthesis were incompetent in cell alignment for initial two-dimensional growth of pellicles. Electron microscopic and confocal laser scanning microscopic studies showed that the fully matured structures are highly packed by matrix-encased cells which have special arrangements. The cells on the surface of the pellicle lie relatively flat and inside longitudinally cross packed. HPLC analysis of the extrapolysaccharide (EPS) hydrolysate from the colonies from LB agar showed a composition with L-fucose, L-rhamnose, D-galactosamine, D-glucosamine, D-galactose, D-glucose, D-mannose. However, that from pellicles showed similar neutral and amino sugar profile but missing galactose. Furthermore, uronic acid analysis of EPS hydrolysates by HPLC showed that mannuronic acid was detected from pellicles not from colonies, indicating the epm-derived polymer is critical for pellicle formation as proved by the epm mutants. This study verified that for the circular pellicle architecture P. alkylphenolica KL28 cells utilized EPS building blocks different from that used for colony construction. These results indicate that P. alkylphenolica KL28 is a clever architect that dictates unique cell arrangements with selected EPS matrix material to construct sophisticated building, circular biofilm pellicles.

Keywords: biofilm, matrix, pellicle, pseudomonas

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Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Reihane Mehrparvar

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Human age could exceed further by altering gene expression through food intaking, although as a consequence of recent century eating patterns, human life-span getting shorter by emerging irregulating in autophagy mechanism, insulin, leptin, gut microbiota which are important etiological factors of type-2 diabetes, obesity, infertility, cancer, metabolic and autoimmune diseases. However, restricted calorie intake and vigorous exercise might be beneficial for losing weight and metabolic regulation in a short period but could not be implementable in the long term as a way of life. Therefore, the lack of a dietary program that is compatible with the genes of the body is essential. Sweet and high-glycemic-index (HGI) foods were associated with type-2 diabetes and cancer morbidity. The neuropsychological perspective characterizes the inclination of sweet and HGI-food consumption as addictive behavior; hence this process engages preference of gut microbiota, neural node, and dopaminergic functions. Moreover, meal composition is not the only factor that affects body hemostasis. In this narrative review, it is believed to attempt to investigate how the body responded to different food intakes and represent an accurate model based on current evidence. Eating frequently and ingesting unassimilable protein and carbohydrates may not be compatible with human genes and could cause impairments in the self-renovation mechanism. This trajectory indicates our body is more adapted to starvation and eating animal meat and marrow. Here has been recommended a model that takes into account three important factors: frequent eating, meal composition, and circadian rhythm, which may offer a promising intervention for obesity, inflammation, cardiovascular, autoimmune disorder, type-2 diabetes, insulin resistance, infertility, and cancer through intensifying autophagy-mechanism and eliminate medical costs.

Keywords: metabolic disease, anti-aging, type-2 diabetes, autophagy

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Authors: Huyen T. Pham, Nhue P. Nguyen, Tien Q. Phi, Phuong T. Dang, Hy G. Le

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Since the marine environmental conditions are extremely different from the other ones, so that marine actinomycetes might produce novel bioactive compounds. Therefore, actinomycete strains were screened from marine water and sediment samples collected from the coastal areas of Northern Vietnam. Ninety-nine actinomycete strains were obtained on starch-casein agar media by dilution technique, only seven strains, named HP112, HP12, HP411, HPN11, HP 11, HPT13 and HPX12, showed significant antibacterial activity against both gram-positive and gram-negative bacteria (Bacillus subtilis ATCC 6633, Staphylococcus epidemidis ATCC 12228, Escherichia coli ATCC 11105). Further studies were carried out with the most active HP411strain against Candida albicans ATCC 10231. This strain could grow rapidly on starch casein agar and other media with high salt containing 7-10% NaCl at 28-30oC. Spore-chain of HP411 showed an elongated and circular shape with 10 to 30 spores/chain. Identification of the strain was carried out by employing the taxonomical studies including the 16S rRNA sequence. Based on phylogenetic and phenotypic evidence it is proposed that HP411 to be belongs to species Streptomyces variabilis. The potent of the crude extract of fermentation broth of HP411that are effective against wide range of pathogens: both gram-positive, gram-negative and fungi. Further studies revealed that the crude extract HP411 could obtain the anticancer activity for cancer cell lines: Hep-G2 (liver cancer cell line); RD (cardiac and skeletal muscle letters cell line); FL (membrane of the uterus cancer cell line). However, the actinomycetes from marine ecosystem will be useful for the discovery of new drugs in the furture.

Keywords: marine actinomycetes, antibacterial, anticancer, Streptomyces variabilis

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Authors: Hairin Taha, Aditya Arya, M. A. Hapipah, A. M. Mustafa

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Plants have been an important source of medicine since ancient times. Pseuduvaria monticola is a rare montane forest species from the Annonaceae family. Traditionally, the plant was used to cure symptoms of fever, inflammation, stomach-ache and also to reduce the elevated levels of blood glucose. Scientifically, we have evaluated the antidiabetic potential of the Pseuduvaria monticola bark methanolic extract on certain in vitro cell based assays, followed by in vivo study. Results from in vitro models displayed PMm upregulated glucose uptake and insulin secretion in mouse pancreatic β-cells. In vivo study demonstrated the PMm down-regulated hyperglycaemia, oxidative stress and elevated levels of pro-inflammatory cytokines in type 2 diabetic rat models. Altogether, the study revealed that Pseuduvaria monticola might be used as a potential candidate for the management of type 2 diabetes and its related complications.

Keywords: type 2 diabetes, Pseuduvaria monticola, insulin secretion, glucose uptake

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Authors: Anne N. Heirman, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Michiel W.M. van den Brekel

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Background: Due to the rising incidence of oropharyngeal squamous cell cancer (OPSCC), many patients are challenged with choosing between transoral(robotic) surgery and radiotherapy, with equal survival and oncological outcomes. Also, functional outcomes are of little difference over the years. With this study, the wants and needs of patients and caregivers are identified to develop a comprehensible patient decision aid (PDA). Methods: The development of this PDA is based on the International Patient Decision Aid Standards criteria. In phase 1, relevant literature was reviewed and compared to current counseling papers. We interviewed ten post-treatment patients and ten doctors from four head and neck centers in the Netherlands, which were transcribed verbatim and analyzed. With these results, the first draft of the PDA was developed. Phase 2 beholds testing the first draft for comprehensibility and usability. Phase 3 beholds testing for feasibility. After this phase, the final version of the PDA was developed. Results: All doctors and patients agreed a PDA was needed. Phase 1 showed that 50% of patients felt well-informed after standard care and 35% missed information about treatment possibilities. Side effects and functional outcomes were rated as the most important for decision-making. With this information, the first version was developed. Doctors and patients stated (phase 2) that they were satisfied with the comprehensibility and usability, but there was too much text. The PDA underwent text reduction revisions and got more graphics. After revisions, all doctors found the PDA feasible and would contribute to regular counseling. Patients were satisfied with the results and wished they would have seen it before their treatment. Conclusion: Decision-making for OPSCC should focus on differences in side-effects and functional outcomes. Patients and doctors found the PDA to be of great value. Future research will explore the benefits of the PDA in clinical practice.

Keywords: head-and-neck oncology, oropharyngeal cancer, patient decision aid, development, shared decision making

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Authors: Mohammed Fayez Al Rez

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Nowadays, there is an unmet clinical need for new small-diameter vascular grafts to overcome the drawbacks of traditional methods used for treatment of widespread cardiovascular diseases. Vascular tissue engineering (VTE) is a promising approach that can be utilized to develop viable vascular grafts by in vitro seeding of functional cells onto a scaffold allowing them to attach, proliferate and differentiate. To achieve this purpose, the scaffold should provide cells with the initial necessary extracellular matrix environment and structure until being able to reconstruct the required vascular tissue. Therefore, producing scaffolds with suitable features is crucial for guiding cells properly to develop the desired tissue-engineered vascular grafts for clinical applications. The main objective of this work is fabrication and characterization of tubular small-diameter ( < 6 mm) bilayered scaffolds for VTE. The scaffolds were prepared via mixing electrospinning approach of biodegradable poly(ε-caprolactone) (PCL) polymer – due to its favorable physicochemical properties – to mimic the natural environment-extracellular matrix. Firstly, tubular nanofibrous construct with inner diameter of 3, 4 or 5 mm was electrospun as inner layer, and secondly, microfibrous construct was electrospun as outer layer directly on the first produced inner layer. To improve the biological properties of PCL, a group of the electrospun scaffolds was immersed in type-1 collagen solution. The morphology and structure of the resulting fibrous scaffolds were investigated by scanning electron microscope. The electrospun nanofibrous inner layer contained fibers measuring 219±35 nm in diameter, while the electrospun microfibrous outer layer contained fibers measuring 1011 ± 150 nm. Furthermore, mechanical, thermal and physical tests were conducted with both electrospun bilayered scaffold types where revealed improved properties. Biological investigations using endothelial, smooth muscle and fibroblast cell line showed good biocompatibility of both tested electrospun scaffolds. Better attachment and proliferation were obviously found when cells were cultured on the scaffolds immersed with collagen due to increasing the hydrophilicity of the PCL. The easy, inexpensive and versatile electrospinning approach used in this work was able to successfully produce double layered tubular elastic structures containing both nanofibers and microfibers to imitate the native vascular structure. The PCL – as a suitable and approved biomaterial for many biomedical and tissue engineering applications – can ensure favorable mechanical properties of scaffolds used for VTE. The VTE approach using electrospun bilayered scaffolds offers optimal solutions and holds significant promises for treatment of many cardiovascular diseases.

Keywords: electrospinning, poly(ε-caprolactone) (PCL), tissue-engineered vascular graft, tubular bilayered scaffolds, vascular cells

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