Search results for: cancer cell apoptosis

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: Hossain A., Miah S., Ray P. K.

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Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.

Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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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: Asmat Nawaz, Ali Koray Erdinc, Burak Gultekin, Muhammad Tayyib, Ceylan Zafer, Kaiying Wang, M. Nadeem Akram

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In this study, a sequential deposition process is used for the fabrication of PEDOT: PSS based inverted planar perovskite solar cell. A small amount of additive deionized water (DI-H₂O) was added into PbI₂ + Dimethyl formamide (DMF) precursor solution in order to increase the solubility of PbI₂ in DMF, and finally to manipulate the surface morphology of the perovskite films. A morphology transition from needle like structure to hexagonal plates, and then needle-like again has been observed as the DI-H2O was added continuously (0.0 wt% to 3.0wt%). The latter one leads to full surface coverage of the perovskite, which is essential for high performance solar cell.

Keywords: charge carrier diffusion lengths, Methylamonium lead iodide, precursor composition, perovskite solar cell, sequential deposition

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Authors: Yuta Kurashina, Chikahiro Imashiro, Kiyoshi Ohnuma, Kenjiro Takemura

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Research objectives and goals: To realize clinical applications of regenerative medicine, a mass cell culture is highly required. In a conventional cell culture, trypsinization was employed for cell detachment. However, trypsinization causes proliferation decrease due to injury of cell membrane. In order to detach cells using an enzyme-free method, therefore, this study proposes a novel cell detachment method capable of detaching adherent cells using acoustic radiation pressure exposed to the dish by the assistance of serum-free medium with ITS liquid medium supplement. Methods used In order to generate acoustic radiation pressure, a piezoelectric ceramic plate was glued on a glass plate to configure an ultrasonic transducer. The glass plate and a chamber wall compose a chamber in which a culture dish is placed in glycerol. Glycerol transmits acoustic radiation pressure to adhered cells on the culture dish. To excite a resonance vibration of transducer, AC signal with 29-31 kHz (swept) and 150, 300, and 450 V was input to the transducer for 5 min. As a pretreatment to reduce cell adhesivity, serum-free medium with ITS liquid medium supplement was spread to the culture dish before exposed to acoustic radiation pressure. To evaluate the proposed cell detachment method, C2C12 myoblast cells (8.0 × 104 cells) were cultured on a ø35 culture dish for 48 hr, and then the medium was replaced with the serum-free medium with ITS liquid medium supplement for 24 hr. We replaced the medium with phosphate buffered saline and incubated cells for 10 min. After that, cells were exposed to the acoustic radiation pressure for 5 min. We also collected cells by using trypsinization as control. Cells collected by the proposed method and trypsinization were respectively reseeded in ø60 culture dishes and cultured for 24 hr. Then, the number of proliferated cells was counted. Results achieved: By a phase contrast microscope imaging, shrink of lamellipodia was observed before exposed to acoustic radiation pressure, and no cells remained on the culture dish after the exposed of acoustic radiation pressure. This result suggests that serum-free medium with ITS liquid inhibits adhesivity of cells and acoustic radiation pressure detaches cells from the dish. Moreover, the number of proliferated cells 24 hr after collected by the proposed method with 150 and 300 V is the same or more than that by trypsinization, i.e., cells were proliferated 15% higher with the proposed method using acoustic radiation pressure than with the traditional cell collecting method of trypsinization. These results proved that cells were able to be collected by using the appropriate exposure of acoustic radiation pressure. Conclusions: This study proposed a cell detachment method using acoustic radiation pressure by the assistance of serum-free medium. The proposed method provides an enzyme-free cell detachment method so that it may be used in future clinical applications instead of trypsinization.

Keywords: acoustic radiation pressure, cell detachment, enzyme free, ultrasonic transducer

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Authors: Naya Masood, Russell Hodgson, Mark Tacey

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Purpose: Patients with acute diverticulitis (AD) have an increased risk of underlying colorectal cancer (CRC); however, those with uncomplicated AD may have the same underlying population risk. This study informs on an Australian AD population who were not routinely offered colonoscopic follow-up. Methods: A 2-year (July 2016 – June 2018) retrospective study of patients admitted with CT-confirmed acute diverticulitis was conducted. CT findings were categorised as ‘complicated’ and ‘uncomplicated’ and were correlated with the detection of cancer in subsequent colonoscopy or follow-up. Results: 67.7% (n=292) of 431 patients were seen to have had complicated AD on an abdominopelvic CT scan. Patients were complicated most commonly due to bowel wall thickening reported on CT (90.4%), perforation (20.2%), or an abscess (12%). Follow-up colonoscopic evaluation was conducted in 52.9% (n=228) of total cases of AD, out of which 156 suffered complicated AD and the rest uncomplicated. None of the uncomplicated AD patients in our cohort were found to have CRC. Of those with complicated AD, six were found to have CRC. Conclusion: The only CRC diagnoses were made in patients with complicated AD. Despite available evidence, a significant proportion of uncomplicated AD patients were still undergoing colonoscopy. There is scope to further safely decrease the number of colonoscopies performed in AD patients.

Keywords: acute diverticulitis, colonoscopy, colorectal cancer, advanced adenoma, complicated diverticulitis

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Authors: Jiun-Nan Hou, Tien-Huang Chen, Wei-June Chen

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Dengue viruses (DENVs) are naturally transmitted between humans by mosquito vectors. Mosquito cells usually survive DENV infection, allowing infected mosquitoes to retain an active status for virus transmission. In this study, we found that DENV2 virus infection in mosquito cells causes the unfolded protein response (UPR) that activates the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway, leading to shutdown of global protein translation in infected cells which was apparently regulated by the PERK signal pathway. According to observation in this study, the PERK signal pathway in DENV2-infected C6/36 cells alleviates ER stress, and reduces initiator and effector caspases, as well as the apoptosis rate via shutdown of cellular proteins. In fact, phosphorylation of eukaryotic initiation factor 2ɑ (eIF2ɑ) by the PERK signal pathway may impair recruitment of ribosomes that bind to the mRNA 5’-cap structure, resulting in an inhibitory effect on canonical cap-dependent cellular protein translation. The resultant pro-survival “byproduct” of infected mosquito cells is undoubtedly advantageous for viral replication. This finding provides insights into elucidating the PERK-mediated modulating web that is actively involved in dynamic protein synthesis, cell survival, and viral replication in mosquito cells.

Keywords: cap-dependent protein translation, dengue virus, endoplasmic reticulum stress, mosquito cells, PERK signal pathway

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Authors: Mokdad Sakhri, Youcef Bouhadda

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Thin film chalcopyrite technology is thus nowadays a solid candidate for photovoltaic cells. The currently used window layer for the solar cell Cu(In,Ga)S2 is our interest point in this work. For this purpose, we have performed a first-principles study of structural, electronic and optical properties for both delafossite transparent conductive oxides Cu (In, Ga)O2 and absorbers films Cu(In,Ga)S2. The calculations have been carried out within the local density functional (LDA) and generalized gradient approximations (GGA) combined with the hubbard potential using norm-conserving pseudopotentials and a plane-wave basis with ABINIT code. We have found the energy gap is :1.6, 2.53, 3.6, 3.8 eV for CuInS2, CuGaS2, CuInO2 and CuGaO2 respectively. The results are in good agreement with experimental results.

Keywords: ABINIT code, DFT, electronic and optical properties, solar-cell absorbers, delafossite transparent conductive oxides

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Authors: Barun Chakrabarti, Dan Nir, Vladimir Yufit, P. V. Aravind, Nigel Brandon

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Fuel cell grade gas-diffusion layer carbon paper (CP) electrodes are subjected to electrophoresis in N,N’-dimethylformamide (DMF) consisting of reduced graphene oxide (rGO). The rGO modified electrodes are compared with CP in a single asymmetric all-vanadium redox battery system (employing a double serpentine flow channel for each half-cell). Peak power densities improved by 4% when the rGO deposits were facing the ion-exchange membrane (cell performance was poorer when the rGO was facing the flow field). Cycling of the cells showed least degradation of the CP electrodes that were coated with rGO in comparison to pristine samples.

Keywords: all-vanadium redox flow batteries, carbon paper electrodes, electrophoretic deposition, reduced graphene oxide

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Authors: Sze Wing Ho, Nagendra P. Shah

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Lactic acid bacteria (LAB) have shown the beneficial effects on human gastrointestinal tract, such as protects diarrhea induced by lactose intolerance or enteric pathogens. Citrulline is a non-protein amino acid and also the precursors of arginine and nitric oxide, it has shown to enhance intestinal barrier function. Citrulline has shown to improve the growth of some strains of LAB, it is important for LAB to have a sufficient cell concentration to contribute the effects. Therefore, the aims of this study were to investigate the effect of combining citrulline with LAB on the anti-adhesion effect against pathogens and the effect on the cell integrity. The effect of citrulline on selected LAB was determined by incubating in 0%, 0.1% or 0.2% citrulline enriched MRS broth for 18 h. The adhesion ability of LAB and the anti-adhesion effect of LAB and citrulline against pathogens were performed on IPEC-J2 cell line. Transepithelial electrical resistance (TEER) assay was used to measure the tight junction (TJ) integrity. TJ proteins (claudin-1, occludin and zonula occluden-1 (ZO-1)) were determined by western blot analysis. It found that the growth of Lactobacillus helveticus ASCC 511 was significantly stimulated by 0.2% citrulline compared with control during 18 h fermentation. The adhesion of L. helveticus ASCC 511 and Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) ASCC 756 was increased when supplemented with citrulline. Citrulline has shown significant inhibitory effect on the adhesion of Escherichia coli PELI0480 (O157:H7), Shigella sonnei ATCC 25931, Staphyloccocus aureus CMCC26003 and Cronobacter sakazakii ATCC 29544. The anti-adhesion effect of L. helveticus ASCC 511, L. bulgaricus ASCC 756 and Lactobacillus paracasei ASCC 276 against Cronobacter sakazakii ATCC 29544 was significantly enhanced with citrulline supplementation. Treatments with citrulline and LAB were able to maintain the TEER of IPEC-J2 cell and shown the positive effect on the TJ proteins. In conclusion, citrulline had stimulating effect on some strains of LAB and determined to improve the adhesion of LAB on intestinal epithelial cell, to enhance the inhibitory effect on enteric pathogens adhesion as well as had beneficial effects on maintaining cell integrity. It implied LAB supplemented with citrulline might have advantageous effects on gastrointestinal tracts.

Keywords: citrulline, lactic acid bacteria, amino acid, anti-adhesion effect, cell integrity

Procedia PDF Downloads 238

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Benyapa Suksuwan

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Introduction: Oxidative stress is identified as the root cause of the development and progression of several diseases as the disproportion of free radicals in the body leads to tissue or cell damage. Polyphenols are the most common antioxidant found in plants and are efficient in capturing oxidative free radicals. Aim of the Study: This study focused on the antioxidant activity of polyphenols extracted from Phyllanthus Emblica L. as oxidative stress plays a vital role in developing and progressing many diseases, including cardiovascular diseases and cancer. Materials and Methods: The plant was extracted using a mixture solvent (ethyl alcohol: water in ratio 8:2). The total phenolic content of P. Emblica extract was determined using the Folin-Cioucalteu method and calculated as gallic acid equivalents (GAE) and various antioxidant assays DPPH and ABTS radical scavenging capacity assays. Results and Discussion: The findings exhibited a strong correlation between antioxidant activity and the total phenol contents. In addition, the IC₅₀ of P. Emblica extract via DPPH and ABTS assays were 68.10 μg/mL ± 0.455, and 49.24 μg/mL ± 0.716, respectively. Furthermore, P. Emblica extract showed antioxidant activities in a concentration-dependent manner. Vitamin C was used as a positive control in the DPPH assay, while Trolox was used as a positive control in the ABTS assay. Conclusions: In conclusion, P. Emblica extract consisted of a high amount of total phenolic content, which possesses potent antioxidant activity. However, further antioxidant activity assays using human cell lines such as SOD, ROS, and RNS scavenging assays and in vitro antioxidant experiments should be performed in order.

Keywords: antioxidant, ABTS scavenging, DPPH scavenging assay, total phenol contents assay, Phyllanthus Emblica L

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Authors: Nada Bezić, Valerija Dunkić, Antonija Markovina, Mirko Rušćić

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Valeriana is a genus of the well-known medicinal plant of Valerianacea family and growing wild in the sub-Mediterranean area. This abstract reports the types and distribution of trichomes and phyto-active composition of the essential oil of the Valeriana tuberosa from mountain Kozjak, near Split, Croatia. Two types of glandular trichomes: peltate (one basal epidermal cell, one short stalk cell and a small head) and capitate trichomes (one basal epidermal cell, one elongated stalk cell) were observed on leaf, using light microscopy. We analyzed the composition of the essential oil of stems and leaves of V. tuberosa species. Water distilled essential oils from aerial parts of investigation plant have been analysed by GC and GC/MS using VF-5ms capillary column. The total yield of oil was 0.2%, based on dry weight of samples. Forty compounds representing 94.1% of the total oil of V. tuberosa. This essential oil was characterized by a high concentration of isovaleric acid (17.2%), geranyl isovalerate (12.2%) and caryophyllene oxide (7.7%). The present study gives additional knowledge about micromorphological traits and secondary metabolites contents on the genus Valeriana.

Keywords: essential oil, isovaleric acid, Valeriana tuberosa, Croatia

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Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen

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Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.

Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team

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Authors: Ella Tyuryumina, Alexey Neznanov

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Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

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Authors: Abir Yahya, Hacen Dhahri, Khalifa Slimi

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The present paper deals with a numerical simulation of temperature field inside a solid oxide fuel cell (SOFC) components. The temperature distribution is investigated using a co-flow planar SOFC comprising the air and fuel channel and two-ceramic electrodes, anode and cathode, separated by a dense ceramic electrolyte. The Lattice Boltzmann method (LBM) is used for the numerical simulation of the physical problem. The effects of inlet temperature, anode thermal conductivity and current density on temperature distribution are discussed. It was found that temperature distribution is very sensitive to the inlet temperature and the current density.

Keywords: heat sources, Lattice Boltzmann method, solid oxide fuel cell, temperature

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Authors: Stephen Daniel Iduh, Evans Chidi Egwin, Oluwatosin Kudirat Shittu

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The process for the development of reliable and eco-friendly metallic Nanoparticles is an important step in the field of Nanotechnology for biomedical application. To achieve this, use of natural sources like biological systems becomes essential. In the present work, extracellular biosynthesis of gold Nanoparticles using aqueous leave and stembark extracts of K. senegalensis has been attempted. The gold Nanoparticles produced were characterized using High Resolution scanning electron microscopy, Ultra Violet–Visible spectroscopy, zeta-sizer Nano, Energy-Dispersive X-ray (EDAX) Spectroscopy and Fourier Transmission Infrared (FTIR) Spectroscopy. The cytotoxicity of the synthesized gold nanoparticles on MCF-7 cell line was evaluated using MTT assay. The result showed a rapid development of Nano size and shaped particles within 5 minutes of reaction with Surface Plasmon Resonance at 520 and 525nm respectively. An average particle size of 20-90nm was confirmed. The amount of the extracts determines the core size of the AuNPs. The core size of the AuNPs decreases as the amount of extract increases and it causes the shift of Surface Plasmon Resonance band. The FTIR confirms the presence of biomolecules serving as reducing and capping agents on the synthesised gold nanoparticles. The MTT assay shows a significant effect of gold nanoparticles which is concentration dependent. This environment-friendly method of biological gold Nanoparticle synthesis has the potential and can be directly applied in cancer therapy.

Keywords: biosynthesis, gold nanoparticles, characterization, calotropis procera, cytotoxicity

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Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli

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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing

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Authors: Bing Yan

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Nanomaterials are widely used in various industrial sectors, biomedicine, and more than 1300 consumer products. Although there is still no standard safety regulation, their potential toxicity is a major concern worldwide. We discovered that nanoparticles target and enter human cells1, perturb cellular signaling pathways2, affect various cell functions3, and cause malfunctions in animals4,5. Because the majority of atoms in nanoparticles are on the surface, chemistry modification on their surface may change their biological properties significantly. We modified nanoparticle surface using nano-combinatorial chemistry library approach6. Novel nanoparticles were discovered to exhibit significantly reduced toxicity6,7, enhance cancer targeting ability8, or re-program cellular signaling machineries7. Using computational chemistry, quantitative nanostructure-activity relationship (QNAR) is established and predictive models have been built to predict biocompatible nanoparticles.

Keywords: nanoparticle, nanotoxicity, nano-bio, nano-combinatorial chemistry, nanoparticle library

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Authors: Roman Matejka, Vaclav Prochazka, Tibor Izak, Jana Stepanovska, Martina Travnickova, Alexander Kromka

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Cell-based impedance spectroscopy is suitable method for electrical monitoring of cell activity especially on substrates that cannot be easily inspected by optical microscope (without fluorescent markers) like decellularized tissues, nano-fibrous scaffold etc. Special sensor for this measurement was developed. This sensor consists of corning glass substrate with gold interdigitated electrodes covered with diamond layer. This diamond layer provides biocompatible non-conductive surface for cells. Also, a special PPFC flow cultivation chamber was developed. This chamber is able to fix sensor in place. The spring contacts are connecting sensor pads with external measuring device. Construction allows real-time live cell imaging. Combining with perfusion system allows medium circulation and generating shear stress stimulation. Experimental evaluation consist of several setups, including pure sensor without any coating and also collagen and fibrin coating was done. The Adipose derived stem cells (ASC) and Human umbilical vein endothelial cells (HUVEC) were seeded onto sensor in cultivation chamber. Then the chamber was installed into microscope system for live-cell imaging. The impedance measurement was utilized by vector impedance analyzer. The measured range was from 10 Hz to 40 kHz. These impedance measurements were correlated with live-cell microscopic imaging and immunofluorescent staining. Data analysis of measured signals showed response to cell adhesion of substrates, their proliferation and also change after shear stress stimulation which are important parameters during cultivation. Further experiments plan to use decellularized tissue as scaffold fixed on sensor. This kind of impedance sensor can provide feedback about cell culture conditions on opaque surfaces and scaffolds that can be used in tissue engineering in development artificial prostheses. This work was supported by the Ministry of Health, grants No. 15-29153A and 15-33018A.

Keywords: bio-impedance measuring, bioreactor, cell cultivation, diamond layer, gold interdigitated electrodes, tissue engineering

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Authors: Taek Hwan Lee, Moon Ho Do, Lalita Subedi, Young Un Park, Sun Yeou Kim

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Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: dolichos lablab, germination, neuroprotection, trigonelline

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Authors: B. Samuel Raj, Solomon R. D. Jebakumar

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Microbial fuel cells (MFCs) are an emerging and promising method for achieving sustainable energy since they can remove contaminated organic matter and simultaneously generate electricity. Our approach was driven in three different ways like Bacterial fuel cell, Soil Microbial fuel cell (Soil MFC) and Plant Microbial fuel cell (Plant MFC). Bacterial MFC: Sulphate reducing bacteria (SRB) were isolated and identified as the efficient electricigens which is able to produce ±2.5V (689mW/m2) and it has sustainable activity for 120 days. Experimental data with different MFC revealed that high electricity production harvested continuously for 90 days 1.45V (381mW/m2), 1.98V (456mW/m2) respectively. Biofilm formation was confirmed on the surface of the anode by high content screening (HCS) and scanning electron Microscopic analysis (SEM). Soil MFC: Soil MFC was constructed with low cost and standard Mudwatt soil MFC was purchased from keegotech (USA). Vermicompost soil (V1) produce high energy (± 3.5V for ± 400 days) compared to Agricultural soil (A1) (± 2V for ± 150 days). Biofilm formation was confirmed by HCS and SEM analysis. This finding provides a method for extracting energy from organic matter, but also suggests a strategy for promoting the bioremediation of organic contaminants in subsurface environments. Our Soil MFC were able to run successfully a 3.5V fan and three LED continuously for 150 days. Plant MFC: Amaranthus candatus (P1) and Triticum aestivium (P2) were used in Plant MFC to confirm the electricity production from plant associated microbes, four uniform size of Plant MFC were constructed and checked for energy production. P2 produce high energy (± 3.2V for 40 days) with harvesting interval of two times and P1 produces moderate energy without harvesting interval (±1.5V for 24 days). P2 is able run 3.5V fan continuously for 10days whereas P1 needs optimization of growth conditions to produce high energy.

Keywords: microbial fuel cell, biofilm, soil microbial fuel cell, plant microbial fuel cell

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Authors: Norah Al Hokbany, Ibrahim Al Jammaz, Basem Al Otaibi, Yousif Al Malki, Subhani M. Okarvi

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Objective: The folate receptor is over-expressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers. Methods: we synthesized ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugates using a straightforward and simple one-step reaction. Radiochemical yields were greater than 95% (decay-corrected) with a total synthesis time of less than 20 min. Results: Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for ⁶⁴Cu-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radio conjugates were associated with cell fractions. Bio-distribution studies in nude mice bearing human KB xenografts demonstrated a significant tumor uptake and favorable bio-distribution profile for ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugate. The uptake in the tumors was blocked by the excess injection of folic acid, suggesting a receptor-mediated process. Conclusion: These results demonstrate that the ⁶⁴Cu-NOTAM-folate conjugate may be useful as a molecular probe for the detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Keywords: folate, receptor, tumor imaging, ⁶⁴Cu-NOTA-folate, PET

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Authors: Sofia G. Meirinho, Luis G. Dias, António M. Peres, Lígia R. Rodrigues

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The emerging development of electrochemical aptasen sors has enabled the easy and fast detection of protein biomarkers in standard and real samples. Biomarkers are produced by body organs or tumours and provide a measure of antigens on cell surfaces. When detected in high amounts in blood, they can be suggestive of tumour activity. These biomarkers are more often used to evaluate treatment effects or to assess the potential for metastatic disease in patients with established disease. Osteopontin (OPN) is a protein found in all body fluids and constitutes a possible biomarker because its overexpression has been related with breast cancer evolution and metastasis. Currently, biomarkers are commonly used for the development of diagnostic methods, allowing the detection of the disease in its initial stages. A previously described RNA aptamer was used in the current work to develop a simple and sensitive electrochemical aptasensor with high affinity for human OPN. The RNA aptamer was biotinylated and immobilized on a gold electrode by avidin-biotin interaction. The electrochemical signal generated from the aptamer–target molecule interaction was monitored electrochemically using cyclic voltammetry in the presence of [Fe (CN) 6]−3/− as a redox probe. The signal observed showed a current decrease due to the binding of OPN. The preliminary results showed that this aptasensor enables the detection of OPN in standard solutions, showing good selectivity towards the target in the presence of others interfering proteins such as bovine OPN and bovine serum albumin. The results gathered in the current work suggest that the proposed electrochemical aptasensor is a simple and sensitive detection tool for human OPN and so, may have future applications in cancer disease monitoring.

Keywords: osteopontin, aptamer, aptasensor, screen-printed electrode, cyclic voltammetry

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Authors: Simon Grossemy, Peggy P. Y. Chan, Pauline M. Doran

Abstract:

Nerve tissue engineering is the main field of research aimed at finding an alternative to autografts as a treatment for nerve injuries. Scaffolds are used as a support to enhance nerve regeneration. In order to successfully design novel scaffolds and in vitro cell culture systems, a deep understanding of the factors affecting nerve regeneration processes is needed. Physical and biological parameters associated with the culture environment have been identified as potentially influential in nerve cell differentiation, including electrical stimulation, exposure to extracellular-matrix (ECM) proteins, dynamic medium conditions and co-culture with glial cells. The mechanisms involved in driving the cell to differentiation in the presence of these factors are poorly understood; the complexity of each of them raises the possibility that they may strongly influence each other. Some questions that arise in investigating nerve regeneration include: What are the best protein coatings to promote neural cell attachment? Is the scaffold design suitable for providing all the required factors combined? What is the influence of dynamic stimulation on cell viability and differentiation? In order to study these effects, scaffolds adaptable to bioreactor culture conditions were designed to allow electrical stimulation of cells exposed to ECM proteins, all within a dynamic medium environment. Gold coatings were used to make the surface of viscose rayon microfiber scaffolds (VRMS) conductive, and poly-L-lysine (PLL) and laminin (LN) surface coatings were used to mimic the ECM environment and allow the attachment of rat PC12 neural cells. The robustness of the coatings was analyzed by surface resistivity measurements, scanning electron microscope (SEM) observation and immunocytochemistry. Cell attachment to protein coatings of PLL, LN and PLL+LN was studied using DNA quantification with Hoechst. The double coating of PLL+LN was selected based on high levels of PC12 cell attachment and the reported advantages of laminin for neural differentiation. The underlying gold coatings were shown to be biocompatible using cell proliferation and live/dead staining assays. Coatings exhibiting stable properties over time under dynamic fluid conditions were developed; indeed, cell attachment and the conductive power of the scaffolds were maintained over 2 weeks of bioreactor operation. These scaffolds are promising research tools for understanding complex neural cell behavior. They have been used to investigate major factors in the physical culture environment that affect nerve cell viability and differentiation, including electrical stimulation, bioreactor hydrodynamic conditions, and combinations of these parameters. The cell and tissue differentiation response was evaluated using DNA quantification, immunocytochemistry, RT-qPCR and functional analyses.

Keywords: bioreactor, electrical stimulation, nerve differentiation, PC12 cells, scaffold

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Authors: Gerard Bray, Arya Bahadori, Sachinka Ranasinghe

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Renal cell carcinoma (RCC) is among the top 10 most common cancers worldwide, where metastatic disease carries a poor prognosis. Herein, we present a 74-year-old male presenting with asymptomatic solitary metachronous metastasis to the gall bladder 4 years following nephrectomy for clear cell RCC. Solitary RCC metastasis to the gall bladder following nephrectomy is rarely reported in the literature and brings with it a clinical conundrum of whether surgical resection or systemic therapy should be utilized. In this case, surgical excision with cholecystectomy was employed without systemic therapy. We, therefore, contribute a rare and interesting case that highlights that metastasectomy of a solitary metastasis can improve survival according to current literature.

Keywords: renal cell carcinoma, gall bladder metastasis, solitary metastasectomy, metachronous

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Authors: Marcin Kruszewski, Barbara Sochanowicz, Sylwia Męczyńska-Wielgosz, Maria Wojewódzka, Lucyna Kapka-Skrzypczak

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Metallic NPs are widely used in a number of applications in industry, science and medicine. Among metallic NPs foreseen to be widely used in medicine are gold nanoparticles (AuNPs) due to their low toxicity, and silver NPs (AgNPs) due to their strong antimicrobial activity. In this study, we compared an effect of AgNPs and gold NPs (AuNPs) on the formation of DNA damage and global DNA methylation and in A2780 and 4T1 cell lines, widely used models of human ovarian carcinoma and murine mammary carcinoma, respectively. The cells were treated with AgNPs coated with citrate (AgNPs(cit) or PEG (AgNPs(PEG), or AuNPs. A global DNA methylation was investigated with ELISA, whereas the formation of DNA damage was investigated by a comet +/- FPG. AgNPs decreased global DNA methylation and increased the formation of DNA lesions in both cell lines. The effect was dependent on the type of NPs used, it's coating, and cell line used. In conclusion, the epigenetic and genotoxic effects of NPs strongly depends on NP nature and cellular context. Epigenetic changes observed upon the action of AgNPs may play a crucial role in NPs-induced changes in protein expression.

Keywords: DNA damage, gold nanoparticles, methylation, silver nanoparticles

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Authors: Cyril Deroy, Agata Rumianek, David R. Greaves, Peter R. Cook, Edmond J. Walsh

Abstract:

Various microfluidic platforms have been developed in the past couple of decades offering experimental methods for the study of cell migration; however, their implementation in the laboratory has remained limited. Some reasons cited for the lack of uptake include the technical complexity of the devices, high failure rate associated with gas-bubbles, biocompatibility concerns with the use of polydimethylsiloxane (PDMS) and equipment/time/expertise requirements for operation and manufacture. As sample handling remains challenging due to the closed format of microfluidic devices, open microfluidic systems have been developed offering versatility and simplicity of use. Rather than confining fluids by solid walls, samples can be accessed directly over the open platform, by removing at least one of the solid boundaries, such as the cover. In this paper, a method for the fabrication of open fluid-walled microfluidic circuits for cell migration studies is introduced, where only materials commonly used by the life-science community are required; tissue culture dishes and cell media. The simplicity of the method, and ability to retrieve cells of interest are two key features of the method. Both passive and active flow-devices can be created in this way. To demonstrate the versatility of the method a cell migration assay is performed, which requires fabricating circuits for establishing chemical gradients, loading cells and incubating, creating chemical gradients, real time imaging of cell migration and finally retrieval of cells. The open architecture has high fidelity as it eliminates air bubble related failures and enables the precise control of gradients. The ability to fabricate custom microfluidic designs in minutes should make this method suitable for use in a wide range of cell migration studies.

Keywords: chemotaxis, fluid walls, gradient generation, open microfluidics

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Authors: Laura Elena De León Prado, Dora Alicia Cortés Hernández, Javier Sánchez

Abstract:

Among the different cancer treatments that are currently used, hyperthermia has a promising potential due to the multiple benefits that are obtained by this technique. In general terms, hyperthermia is a method that takes advantage of the sensitivity of cancer cells to heat, in order to damage or destroy them. Within the different ways of supplying heat to cancer cells and achieve their destruction or damage, the use of magnetic nanoparticles has attracted attention due to the capability of these particles to generate heat under the influence of an external magnetic field. In addition, these nanoparticles have a high surface area and sizes similar or even lower than biological entities, which allow their approaching and interaction with a specific region of interest. The most used magnetic nanoparticles for hyperthermia treatment are those based on iron oxides, mainly magnetite and maghemite, due to their biocompatibility, good magnetic properties and chemical stability. However, in order to fulfill more efficiently the requirements that demand the treatment of magnetic hyperthermia, there have been investigations using ferrites that incorporate different metallic ions, such as Mg, Mn, Co, Ca, Ni, Cu, Li, Gd, etc., in their structure. This paper reports the synthesis of nanosized Mg_xMn_1-xFe₂O₄ (x = 0.3 and 0.4) ferrites by sol-gel method and their evaluation in terms of heating capability and in vitro hemolysis to determine the potential use of these nanoparticles as thermoseeds for the treatment of cancer by magnetic hyperthermia. It was possible to obtain ferrites with nanometric sizes, a single crystalline phase with an inverse spinel structure and a behavior near to that of superparamagnetic materials. Additionally, at concentrations of 10 mg of magnetic material per mL of water, it was possible to reach a temperature of approximately 45°C, which is within the range of temperatures used for the treatment of hyperthermia. The results of the in vitro hemolysis assay showed that, at the concentrations tested, these nanoparticles are non-hemolytic, as their percentage of hemolysis is close to zero. Therefore, these materials can be used as thermoseeds for the treatment of cancer by magnetic hyperthermia.

Keywords: ferrites, heating capability, hemolysis, nanoparticles, sol-gel

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