Search results for: in vivo imaging

Authors: S. Alireza Mirghasemi, Elly Trepman, Mohammad Saleh Sadeghi, Narges Rahimi Gabaran, Shervin Rashidinia

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Bone marrow edema syndrome (BMES) is an uncommon and self-limited syndrome characterized by atraumatic extremity pain with unknown of etiology. Symptom onset may include sudden or gradual swelling and pain at rest or during activity, usually at night. This syndrome mostly affects middle-aged men and younger women who have pain in the lower extremities. The most common sites involved with BMES, in decreasing order of frequency, are the bones about the hip, knee, ankle, and foot. The diagnosis of BMES is made with magnetic resonance imaging to exclude other causes of bone marrow edema. The correct diagnosis often is delayed because of the low prevalence and nonspecific signs in the foot and ankle. This delay may intensify bone pain and impair patient function and quality of life. The goal of BMES treatment is to relieve pain and shorten disease duration. Treatment options are limited and may include symptomatic treatment, pharmacologic treatment, and surgery.

Keywords: transient osteoporosis, bone marrow edema syndrome, iloprost, bisphosphonates

Procedia PDF Downloads 363

Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

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Authors: A. Matiushkina, A. Bazhenova, I. Litvinov, E. Kornilova, A. Dubavik, A. Orlova

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Magnetic-luminescent complexes based on superparamagnetic iron oxide nanoparticles (SPIONs) and semiconductor quantum dots (QDs) have been recognized as a new class of materials that have high potential in modern medicine. These materials can serve for theranostics of oncological diseases, and also as a target agent for drug delivery. They combine the qualities characteristic of magnetic nanoparticles, that is, magneto-controllability and the ability to local heating under the influence of an external magnetic field, as well as phosphors, due to luminescence of which, for example, early tumor imaging is possible. The complexity of creating complexes is the energy transfer between particles, which quenches the luminescence of QDs in complexes with SPIONs. In this regard, a relatively new type of alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs is used in our work. The presence of a sufficiently thick gradient semiconductor shell in alloyed QDs makes it possible to reduce the probability of energy transfer from QDs to SPIONs in complexes. At the same time, Forster Resonance Energy Transfer (FRET) is a perfect instrument to confirm the formation of complexes based on QDs and different-type energy acceptors. The formation of complexes in the aprotic bipolar solvent dimethyl sulfoxide is ensured by the coordination of the carboxyl group of the stabilizing QD molecule (L-cysteine) on the surface iron atoms of the SPIONs. An analysis of the photoluminescence (PL) spectra has shown that a sequential increase in the SPIONs concentration in the samples is accompanied by effective quenching of the luminescence of QDs. However, it has not confirmed the formation of complexes yet, because of a decrease in the PL intensity of QDs due to reabsorption of light by SPIONs. Therefore, a study of the PL kinetics of QDs at different SPIONs concentrations was made, which demonstrates that an increase in the SPIONs concentration is accompanied by a symbatic reduction in all characteristic PL decay times. It confirms the FRET from QDs to SPIONs, which indicates the QDs/SPIONs complex formation, rather than a spontaneous aggregation of QDs, which is usually accompanied by a sharp increase in the percentage of the QD fraction with the shortest characteristic PL decay time. The complexes have been studied by the magnetic circular dichroism (MCD) spectroscopy that allows one to estimate the response of magnetic material to the applied magnetic field and also can be useful to check SPIONs aggregation. An analysis of the MCD spectra has shown that the complexes have zero residual magnetization, which is an important factor for using in biomedical applications, and don't contain SPIONs aggregates. Cell penetration, biocompatibility, and stability of QDs/SPIONs complexes in cancer cells have been studied using HeLa cell line. We have found that the complexes penetrate in HeLa cell and don't demonstrate cytotoxic effect up to 25 nM concentration. Our results clearly demonstrate that alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs can be successfully used in complexes with SPIONs reached new hybrid nanostructures, which combine bright luminescence for tumor imaging and magnetic properties for targeted drug delivery and magnetic hyperthermia of tumors. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and was financially supported by Government of Russian Federation, Grant 08-08.

Keywords: alloyed quantum dots, magnetic circular dichroism, magneto-luminescent complexes, superparamagnetic iron oxide nanoparticles

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

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The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: Hoda Mahgoub, Abeer Hanafy

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Linagliptin (LNG) belongs to dipeptidyl-peptidase-4 (DPP-4) inhibitor class. DPP-4 inhibitors represent a new therapeutic approach for the treatment of type 2 diabetes in adults. The aim of this work was to develop and validate an accurate and reproducible HPLC method for the determination of LNG with high sensitivity in rat plasma. The method involved separation of both LNG and pindolol (internal standard) at ambient temperature on a Zorbax Eclipse XDB C18 column and a mobile phase composed of 75% methanol: 25% formic acid 0.1% pH 4.1 at a flow rate of 1.0 mL.min-1. UV detection was performed at 254nm. The method was validated in compliance with ICH guidelines and found to be linear in the range of 5–1000ng.mL-1. The limit of quantification (LOQ) was found to be 5ng.mL-1 based on 100µL of plasma. The variations for intra- and inter-assay precision were less than 10%, and the accuracy values were ranged between 93.3% and 102.5%. The extraction recovery (R%) was more than 83%. The method involved a single extraction step of a very small plasma volume (100µL). The assay was successfully applied to an in-vivo pharmacokinetic study of LNG in rats that were administered a single oral dose of 10mg.kg-1 LNG. The maximum concentration (Cmax) was found to be 927.5 ± 23.9ng.mL-1. The area under the plasma concentration-time curve (AUC0-72) was 18285.02 ± 605.76h.ng.mL-1. In conclusion, the good accuracy and low LOQ of the bioanalytical HPLC method were suitable for monitoring the full pharmacokinetic profile of LNG in rats. The main advantages of the method were the sensitivity, small sample volume, single-step extraction procedure and the short time of analysis.

Keywords: HPLC, linagliptin, pharmacokinetic study, rat plasma

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Somit Dutta, Pallab Kar, Arnab Kumar Chakraborty, Arnab Sen, Tapas Kumar Chaudhuri

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In the present study three species of Clerodendrum; Clerodendrum indicum, Volkameria inermis and Clerodendrum colebrookianum were used to investigate the possible activity against oxidative stress. A detailed in-vivo and in-vitro antioxidant profiling, directly associated with inflammation-related carcinogenesis, has been executed with a motive to evaluate the free radical scavenging activity of Clerodendrum extract. Measurement of cell viability and ROS generation in HEK-293 (Human Embryonic Kidney Cell Line) cells was also estimated. The immune cell proliferative properties (MTT) and in-vitro assay for evaluation of their antioxidant activities including hydroxyl radical, nitric oxide, singlet oxygen, peroxinitrate and hydrogen peroxide, etc. were investigated. GC-MS and FTIR analyses have been performed to identify the active biological compounds. These active biological compounds were further studied to assess their potential medicinal properties, aided by molecular docking and interaction analysis between the active compounds and different proteins related to oxidative stress leading to progression of carcinogenesis. The research article clearly demonstrates the role of ROS in various phases of carcinogenesis. Therefore, the antioxidant and free radical scavenging capacity of all the Clerodendrum species might prove beneficial for the immune system. It might be concluded that this plant species offers great promise for cancer prevention and therapy due to the presence of several bioactive compounds and potent antioxidant capacity of C. colebrookianum.

Keywords: antioxidant, cancer, oxidative stress, reactive oxygen species (ROS)

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Authors: L. Hamsaveni, Navya Prakash, Suresha

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Document Image Analysis recognizes text and graphics in documents acquired as images. An approach without Optical Character Recognition (OCR) for degraded document image analysis has been adopted in this paper. The technique involves document imaging methods such as Image Fusing and Speeded Up Robust Features (SURF) Detection to identify and extract the degraded regions from a set of document images to obtain an original document with complete information. In case, degraded document image captured is skewed, it has to be straightened (deskew) to perform further process. A special format of image storing known as YCbCr is used as a tool to convert the Grayscale image to RGB image format. The presented algorithm is tested on various types of degraded documents such as printed documents, handwritten documents, old script documents and handwritten image sketches in documents. The purpose of this research is to obtain an original document for a given set of degraded documents of the same source.

Keywords: grayscale image format, image fusing, RGB image format, SURF detection, YCbCr image format

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Authors: Omid Gholipoor Bashiri, Ghafur Mosavi, Aliasghar Behnamghader, Seyed Mahmood Rabiee

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Objective: To determine the effect of selected bone graft on the compression properties of radial bone in rabbit. Design-Experimental in vivo study. Animals: A total of 45 adult male New Zealand white rabbits. Procedures: The rabbits were anesthetized and a one-cm-full thickness piece of radial bone was removed using oscillating saw in the all rabbit. The rabbits were divided into 5 groups on the basis of the material used to fill the bone defect: group 1: the paste of bone cement calcium phosphate; group II: the paste of calcium phosphate mixture with type I collagen; group III: tricalcium phosphate mixed with hydroxyapatite (TCP & HP) with 5% porosity; group IV: the same scaffold as group III with 10% porosity; and group V: the same scaffold as group III and IV with 20% porosity, with 9 rabbits in each group. Subsequently subdivided into 3 subgroups of 3 rabbits each. Results: There was a significant increase in compression properties of radial bone in the group II and V in 2nd and 3rd months as compared with groups I, III and IV. The mean endurable crack-strength in group II and V were slightly higher than that of normal radius (P<0.05). Conclusion and clinical relevance: Application of calcium phosphate paste with type I collagen and scaffold of tricalcium phosphate with hydroxyapatite having 20% porosity indicated to have positive effect in integral formation of qualitative callus at the site of fracture and early re-organization of callus to regain mechanical strength too.

Keywords: calcium phosphate, tricalcium phosphate, hydroxyapatite, radial bone, compressive properties, porosity, type i collagen, rabbit

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Authors: Afiqah Shafify Amran, Siti Aisyah Shamsudin, Nurul Yuziana Mohd Yusof

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Cadmium Sulphide (CdS) from group II-IV quantum dots with good optical properties was successfully synthesized by using the simple colloidal method. Capping them with ligand Polyethylinamine (PEI) alters the surface defect of CdS while, thioglycolic acid (TGA) was added to the reaction as a stabilizer. Due to their cytotoxicity, we decided to conjugate them with the protein cage nanoparticles. In this research, we used capsid of Cowpea Chlorotic Mottle Virus (CCMV) to package the CdS because they have the potential to serve in drug delivery, cell targeting and imaging. Adding Sodium Hydroxide (NaOH) changes the pH of the systems hence the isoelectric charge is adjusted. We have characterized and studied the morphology and the optical properties of CdS and CdS-CCMV by transmitted electron microscopic (TEM), UV-Vis spectroscopy, photoluminescence spectroscopy, UV lamp and Fourier transform infrared spectroscopy (FTIR), respectively. The results obtained suggest that the protein cage nanoparticles do not affect the optical properties of CdS.

Keywords: cadmium sulphide, cowpea chlorotic mottle virus, protein cage nanoparticles, quantum dots

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Authors: Anil P. Dewani, Ravindra L. Bakal, Anil V. Chandewar

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Present work demonstrates the applicability of high-performance liquid chromatography (HPLC) with UV detection for the determination of malondialdehyde as malondialdehyde-thiobarbituric acid complex (MDA-TBA) in-vivo in rats. The HPLC-UV method for MDA-TBA was achieved by isocratic mode on a reverse-phase C18 column (250mm×4.6mm) at a flow rate of 1.0mLmin−1 followed by UV detection at 278 nm. The chromatographic conditions were optimized by varying the concentration and pH followed by changes in percentage of organic phase optimal mobile phase consisted of mixture of water (0.2% Triethylamine pH adjusted to 2.3 by ortho-phosphoric acid) and acetonitrile in ratio (80:20 % v/v). The retention time of MDA-TBA complex was 3.7 min. The developed method was sensitive as limit of detection and quantification (LOD and LOQ) for MDA-TBA complex were (standard deviation and slope of calibration curve) 110 ng/ml and 363 ng/ml respectively. The method was linear for MDA spiked in plasma and subjected to derivatization at concentrations ranging from 100 to 1000 ng/ml. The precision of developed method measured in terms of relative standard deviations for intra-day and inter-day studies was 1.6–5.0% and 1.9–3.6% respectively. The HPLC method was applied for monitoring MDA levels in rats subjected to chronic treatment of ciprofloxacin (CFL) (5mg/kg/day) for 21 days. Results were compared by findings in control group rats. Mean peak areas of both study groups was subjected for statistical treatment to unpaired student t-test to find p-values. The p value was < 0.001 indicating significant results and suggesting increased MDA levels in rats subjected to chronic treatment of CFL of 21 days.

Keywords: MDA, TBA, ciprofloxacin, HPLC-UV

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Authors: Mateen A. Khan, Elizabeth J. Theil, Dixie J. Goss

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Cellular iron homeostasis is accomplished by the coordinated regulated expression of iron uptake, storage, and export. Iron regulate the translation of ferritin and mitochondrial aconitase iron responsive element (IRE)-mRNA by interaction with an iron regulatory protein (IRPs). Iron increases protein biosynthesis encoded in iron responsive element. The noncoding structure IRE-mRNA, approximately 30-nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. Fluorescence anisotropy measurements showed the presence of one binding site on IRP1 for ferritin and mitochondrial aconitase IRE-mRNA. Scatchard analysis revealed the binding affinity (Kₐ) and average binding sites (n) for ferritin and mitochondrial aconitase IRE-mRNA were 68.7 x 10⁶ M⁻¹ and 9.2 x 10⁶ M⁻¹, respectively. In order to understand the relative importance of equilibrium and stability, we further report the contribution of electrostatic interactions in the overall binding of two IRE-mRNA with IRP1. The fluorescence quenching of IRP1 protein was measured at different ionic strengths. The binding affinity of IRE-mRNA to IRP1 decreases with increasing ionic strength, but the number of binding sites was independent of ionic strength. Such results indicate a differential contribution of electrostatics to the interaction of IRE-mRNA with IRP1, possibly related to helix bending or stem interactions and an overall conformational change. Selective destabilization of ferritin and mitochondrial aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.

Keywords: IRE-mRNA, IRP1, binding, ionic strength

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Authors: Muhammad nor Farhan Sa'At, Xin Y. Lim, Terence Y. C. Tan, Siti Hajar M. Rosli, Syazwani S. Ali, Ami F. Syed Mohamed

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INTRODUCTION: Hemp (Cannabis sativa subsp. sativa), commonly used for industrial purposes, differs from marijuana by containing lower levels of delta-9-tetrahydronannabidiol- the principal psychoactive constituent in cannabis. Due to its non-psychoactive nature, there has been growing interest in hemp’s therapeutic potential, which has been investigated through pre-clinical and clinical study modalities. OBJECTIVE: To provide an overview of the current landscape of hemp research, through recent scientific findings specific to the pharmacological effects of the medicinal hemp plant and its derived compounds. METHODS: This review was conducted through a systematic search strategy according to the preferred reporting items for systematic review and meta-analysis-ScR (PRISMA-ScR) checklist on electronic databases including MEDLINE, OVID (OVFT, APC Journal Club, EBM Reviews), Cochrane Library Central and Clinicaltrials.gov. RESULTS: From 65 primary articles reviewed, there were 47 pre-clinical studies related to medicinal hemp. Interestingly, the hemp derivatives showed several potential activities such as anti-oxidative, anti-hypertensive, anti-inflammatory, anti-diabetic, anti-neuroinflammatory, anti-arthritic, anti-acne, and anti-microbial activities. Renal protective effects and estrogenic properties were also exhibited in vitro. CONCLUSION: Medicinal hemp possesses various pharmacological effects tested in vitro and in vivo. Information provided in this review could be used as tool to strengthen the study design of future clinical trial research.

Keywords: Preclinical, Herbal Medicine, Hemp, Cannabis

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Authors: Daniel M. Barry

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Since more than half a century ago, attempts have been made to culture cells and embryos outside the body (in vitro or ex vivo). This was done with different culture media and in various “incubators”. In the present study two different culture media were used: a standard TCM-199 culture medium and first trimester amniotic fluid (BAF) collected sterilely from pregnant cows after slaughter. Two different culture conditions were also investigated, the standard laboratory CO2 incubator versus culturing bovine embryos in the vagina of a goat doe. Two experiments were done: Firstly the permeability of different receptacles to CO2 gas was analyzed for possible culture in the vagina. Four-well plates and straws were used to incubate TCM-199 and BAF for a period of 120 h in the presence or absence of 5% CO2 gas. The pH values were measured and recorded every 24 h. In the second experiment pre-compacted morula stage bovine embryos were cultured in the above culture media in sealed 0.25 mL straws in a standard laboratory incubator and in the vagina of a goat doe. Evaluation was done on (1) stage of development and (2) number of blastomeres after 96 h of culture. In the first experiment it was shown that the CO2 gas diffused out of the 4-well plate as well as through the wall of the straws in the absence of CO2 gas, while in the presence of CO2 the pH of both media stabilized between 7.3 and 7.5. This meant that the semen straws were permeable to CO2 gas and could therefore be used as receptacles for culturing early stage bovine embryos. In the second experiment no statistical differences (p>0.05) were found in the number of pre-compacted bovine embryos that developed to the blastocyst stage, or the hatched blastocyst stage, neither for the culture medium used, or the method of culturing in the two incubators. Neither was there any difference (p>0.05) in the number of blastomeres that developed at the blastocyst stage between the two types of incubators. The bovine embryos tended to develop more blastomeres when cultured in BAF than when cultured in TCM-199 in both the standard laboratory incubator and when using the vagina of a goat doe as an incubator.

Keywords: alternative culture, bovine embryos, vagina, bovine amniotic fluid, incubator

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Authors: Woogul Lee, Johnmarshall Reeve

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Learners’ perceived autonomy predicts learners’ interest, engagement, and learning. To understand these processes, we conducted an fMRI experiment. In this experiment, participants saw the national flag and were asked to rate how much they freely wanted to learn about that particular national flag. The participants then learned the characteristics of the national flag. Results showed that (1) the degree of participants’ perceived autonomy was positively correlated with the degree of insula activity, (2) participants’ early-trial insula activity predicted corresponding late-trial dorsolateral prefrontal cortex activity, and (3) the degree of dorsolateral prefrontal cortex activity was positively correlated with the degree of participants’ learning about the characteristics of the national flag. Results suggest that learners’ perceived autonomy predicts learning through the mediation of insula activity associated with intrinsic satisfaction and 'pure self' processes.

Keywords: insular cortex, autonomy, self-determination, dorsolateral prefrontal cortex

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Hanaa M. Abdelgawad, Mona Safar, Ayman M. Wahba

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Real-time image and video processing is a demand in many computer vision applications, e.g. video surveillance, traffic management and medical imaging. The processing of those video applications requires high computational power. Therefore, the optimal solution is the collaboration of CPU and hardware accelerators. In this paper, a Canny edge detection hardware accelerator is proposed. Canny edge detection is one of the common blocks in the pre-processing phase of image and video processing pipeline. Our presented approach targets offloading the Canny edge detection algorithm from processing system (PS) to programmable logic (PL) taking the advantage of High Level Synthesis (HLS) tool flow to accelerate the implementation on Zynq platform. The resulting implementation enables up to a 100x performance improvement through hardware acceleration. The CPU utilization drops down and the frame rate jumps to 60 fps of 1080p full HD input video stream.

Keywords: high level synthesis, canny edge detection, hardware accelerators, computer vision

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Authors: Cemre Polat, Dogan B. Saydam, Mustafa Soyler, Coskun Ozalp

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In this study, the flow structure was investigated by particle imaging velocimetry (PIV) method at Re = 26000 for two different rectangular cylinders placed perpendicular and parallel to the flow direction. After obtaining streamwise and spanwise velocity data, average vorticity, streamlines, velocity magnitude, turbulence kinetic energy, root mean square of streamwise and spanwise velocity fluctuations are calculated, and critical points of flow structure are explained. As a result of the study, it was seen that the vertical configuration has less effect on the flow structure in the back region of the body compared to the horizontal configuration. When the streamwise velocity component is examined in both configurations, it is seen that the negative velocity component is stronger on the long sides compared to the short sides. It has been observed that the vertically positioned cylinder expands the flow separation point compared to the horizontally positioned cylinder; also the vertical cylinder creates an increase in turbulence kinetic energy compared to the horizontal cylinder.

Keywords: bluff body, flow characteristics, PIV, rectangular cylinder

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Authors: O. Maranci, A. B. Tugrul

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Scintigraphy is an imaging method of nuclear events provoked by collisions or charged current interactions with radiation. It is used for diagnostic test used in nuclear medicine via radiopharmaceuticals emitting radiation which is captured by gamma cameras to form two-dimensional images. Liver scintigraphy is widely used in nuclear medicine.Tc-99m and Cr-51 gamma radioisotopes can be used for this purpose. Cr-51 usage is more important for patients’ organ dose that has higher energy and longer half-life as compared to Tc-99m. In this study, it is aimed to determine the required dose for critical organs of patient through liver scintigraphy via Cr-51 gamma radioisotope. Experimental studies were conducted on patients even though conducting experimental studies on patients is extremely difficult for determination of critical organ doses. Torso phantom was utilized to simulate the liver scintigraphy by using 20 mini packages of Cr-51 that were placed on the organ. The radioisotope was produced by irradiation in central thimble of TRIGA MARK II Reactor at 250 KW power. As the results of the study, critical organ doses were determined and evaluated with different critic organs.

Keywords: critical organ doses, liver, scintigraphy, TRIGA Mark-II

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Authors: Daniel Canales, Fabián Alvarez, Pablo Varela, Marcela Saavedra, Claudio García, Paula Zapata

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Calcium oxide nanoparticles (n-CaO) ca. 8 nm were obtained from eggshell waste. The n-CaO was incorporated into Poly(lactic acid) PLA matrix in 10 and 20 wt.% of filler content by electrospinning process to obtain PLA/n-CaO nanocomposite fibers as a potential use in scaffold for bone tissue regeneration. The fibers morphology and diameter were homogeneity, the PLA had a diameter of 2.2 ± 0.8 µm and, with the nanoparticles incorporation (20wt.%), reached ca. 2.9 ± 0.9 µm. The PLA/n-CaO nanocomposites fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after 7 days in Simulated Body Solution (SBF). The biocidal and biological properties of PLA/n-Cao with 20 wt.% were evaluated, showing a 30% reduction in bacterial viability against S. aureus and 11% for E. coli after 6 hours of bacterial suspensions exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, permitting the cell adhesion and proliferation in Roswell Park Memorial Institute medium (RPMI). The PLA/n-CaO with 20 wt.% of nanoparticles showed a higher capacity to promote the osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after 7 days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of scaffolds prepared, the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material improve the healing process.

Keywords: electrospun scaffolds, PLA based nanocomposites, calcium oxide nanoparticles, bioactive materials, tissue engineering

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Authors: Thangavelu Muthukumar, Thotapalli Parvathaleswara Sastry

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Collagen is the most abundantly available connective tissue protein, which is being used as a biomaterial for various biomedical applications. Presently, fish wastes are disposed improperly which is causing serious environmental pollution resulting in offensive odour. Fish scales are promising source of Type I collagen. Medicinal plants have been used since time immemorial for treatment of various ailments of skin and dermatological disorders especially cuts, wounds, and burns. Developing biomaterials from the natural sources which are having wound healing properties within the search of a common man is the need of hour, particularly in developing and third world countries. With these objectives in view we have developed a wound dressing material containing fish scale collagen (FSC) incorporated with Macrotyloma uniflorum plant extract (PE). The wound dressing composite was characterized for its physiochemical properties using conventional methods. SEM image revealed that the composite has fibrous and porous surface which helps in transportation of oxygen as well as absorbing wound fluids. The biomaterial has shown 95% biocompatibility with required mechanical strength and has exhibited antimicrobial properties. This biomaterial has been used as a wound dressing material in experimental wounds of rats. The healing pattern was evaluated by macroscopic observations, panimetric studies, biochemical, histopathological observations. The results showed faster healing pattern in the wounds treated with CSPE compared to the other composites used in this study and untreated control. These experiments clearly suggest that CSPE can be used as wound/burn dressing materials.

Keywords: collagen, wound dressing, Macrotyloma uniflorum, burn dressing

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Authors: Elbadawy A. Kamoun

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Magnetically responsive hydrogel nanocomposite (NCH) based on composites of superparamagnetic of Fe3O4 nano-particles and temperature responsive hydrogel matrices were developed. The nanocomposite hydrogel system based on the temperature sensitive N-isopropylacrylamide hydrogels crosslinked by poly(ethylene glycol)-400 dimethacrylate (PEG400DMA) incorporating with chitosan derivative, was synthesized and characterized. Likewise, the NCH system was synthesized by visible-light free radical photopolymerization, using carboxylated camphorquinone-amine system to avoid the common risks of the use of UV-light especially in hyperthermia treatment. Superparamagnetic of iron oxide nanoparticles were introduced into the hydrogel system by polymerizing mixture technique and monomer solution. FT-IR with Raman spectroscopy and Wide angle-XRD analysis were utilized to verify the chemical structure of NCH and exfoliation reaction for nanoparticles, respectively. Additionally, morphological structure of NCH was investigated using SEM and TEM photographs. The swelling responsive of the current nanocomposite hydrogel system with different crosslinking conditions, temperature, magnetic field efficiency, and the presence effect of magnetic nanoparticles were evaluated. Notably, hydrolytic degradation of this system was proved in vitro application. While, in-vivo release profile behavior is under investigation nowadays. Moreover, the compatibility and cytotoxicity tests were previously investigated in our studies for photoinitiating system. These systems show promised polymeric material candidate devices and are expected to have a wide applicability in various biomedical applications as mildly.

Keywords: hydrogel nanocomposites, tempretaure-responsive hydrogel, superparamagnetic nanoparticles, hyperthermia therapy

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Authors: Sajjad Jafari, Reza Akbari

Abstract:

Background and Aim: Chrysin, a flavonoid compound found in medicinal plants, honey, and propolis, has potential biological activities that make it an important perspective in the treatment of infectious and cancer diseases. The aim of this review study is to evaluate the biological activities of chrysin in the treatment of infectious and cancer diseases. Material and Methods: The present study is a review study that searched reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using keywords such as antimicrobial, antifungal, chrysin, anticancer, antioxidants, and infectious diseases. The researchers examined 25 articles to determine the biological activities of chrysin. Results: Chrysin has high inhibitory or lethal activities on gram-positive and gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Enterococcus faeces. It also has anti-biofilm effects and antifungal effects on strains such as Aspergillus niger and Candida albicans. Chrysin also has anticancer effects on various cancers, including colorectal cancer, pancreatic cancer, breast cancer, and MCF-7 cancer, which have been confirmed in vitro and in vivo. Conclusion: Chrysin has the potential as an important therapeutic option in the treatment of infectious and cancer diseases. Its high antimicrobial and anticancer activities, combined with its low toxicity in nanoparticle form, make it a promising candidate for further clinical trials. The production of anti-microbial and anti-cancer drugs from natural substances, such as chrysin, is a valuable contribution to the field of medicine.

Keywords: chrysin, antimicrobial, anticancer, infectious diseases

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Authors: T. Scattolin, E. Cavarzerani, F. Visentin, F. Rizzolio

Abstract:

Organopalladium compounds have recently attracted attention for their high stability even under physiological conditions and, above all, for their remarkable in vitro cytotoxicity towards cisplatin-resistant cell lines. Among the organopalladium derivatives, those bearing at least one N-heterocyclic carbene ligand (NHC) and the Pd(II)-η³-allyl fragment have exhibited IC₅₀ values in the micro and sub-micromolar range towards several cancer cell lines in vitro and in some cases selectivity towards cancerous vs. non-tumorigenic cells. Herein, a selection of allyl and indenyl palladates were synthesized using a solvent-free method consisting of grinding the corresponding palladium precursors with different saturated and unsaturated azolium salts. All compounds have been fully characterized by NMR, XRD and elemental analyses. The intramolecular H, Cl interaction has been elucidated and quantified using the Voronoi Deformation Density scheme. Most of the complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with I₅₀ values comparable to or even lower than cisplatin. Interestingly, the potent anticancer activity was also confirmed in a high-serous ovarian cancer (HGSOC) patient-derived tumoroid, with a clear superiority of this class of compounds over classical platinum-based agents. Finally, preliminary enzyme inhibition studies of the synthesized palladate complexes against the model TrxR show that the compounds have high activity comparable to or even higher than auranofin and classical Au(I) NHC complexes. Based on such promising data, further in vitro and in vivo experiments and in-depth mechanistic studies are ongoing in our laboratories.

Keywords: anticancer activity, palladium complexes, organoids, indenyl and allyl ligands

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Authors: Samira Khalaji, , Fenneke Klein Jan, Kay-E. Gottschalk, Eugenia Makrantonaki, Karin Scharffetter-Kochanek

Abstract:

Biological aging is a multi-dimensional process that takes place over a whole range of scales from the nanoscopic alterations within individual cells, over transformations in tissues and organs and to changes of the whole organism. On the single cell level, aging involves mutation of genes, differences in gene expression levels as well as altered posttranslational modifications of proteins. A variety of proteins is affected, including proteins of the cell cytoskeleton and migration machinery. Previous work quantified the expression of cytoskeleton proteins on the gene and protein levels in senescent and young fibroblasts. Their results show that senescent skin fibroblasts have an upregulated expression of the intermediate filament (IF) protein vimentin in contrast to actin and tubulin, which are downregulated. IFs play an important role in providing mechanical stability of cells. However, the mechanical properties of IFs depending on cellular senescence or age of the donor has not been studied so far. Hence, we employed passive microrheology on primary human dermal fibroblasts from female donors with age of 28 years (young) and 86 years (old) as model of in vivo aging and human normal dermal fibroblast from 11-year old male with CPD 17-35 (young) and CPD 58-59 (senescence) as a model of in vitro replicative senescence. In contrast to the expectations, our primary results show no significant differences in the viscoelastic properties of fibroblasts depending on age of the donor or cellular replicative senescence.

Keywords: aging, cytoskeleton, fibroblast, mechanical properties

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Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

Abstract:

To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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Authors: A. Reum Son, Jin Seon Kwon, Seung Hun Park, Hai Bang Lee, Moon Suk Kim

Abstract:

These days, stem cell therapy is focused on for promising source of treatment in clinical human disease. As a supporter of stem cells, in situ-forming hydrogels with growth factors and cells appear to be a promising approach in tissue engineering. To examine osteogenic differentiation of hTMSCs which is one of mesenchymal stem cells in vivo in an injectable hydrogel, we use a methoxy polyethylene glycol-polycaprolactone blockcopolymer (MPEG-PCL) solution with osteogenic factors. We synthesized MPEG-PCL hydrogel and measured viscosity to check sol-gel transition. In order to demonstrate osteogenic ability of hTMSCs, we conducted in vitro osteogenesis experiment. Then, to confirm the cell cytotoxicity, we performed WST-1 with hTMSCs and MPEG-PCL. As the result of in vitro experiment, we implanted cell and hydrogel mixture into animal model and checked degree of osteogenesis with histological analysis and amount of expression genes. Through these experimental data, MPEG-PCL hydrogel has sol-gel transition in temperature change and is biocompatible with stem cells. In histological analysis and gene expression, hTMSCs are very good source of osteogenesis with hydrogel and will use it to tissue engineering as important treatment method. hTMSCs could be a good adult stem cell source for usability of isolation and high proliferation. When hTMSCs are used as cell therapy method with in situ-formed hydrogel, they may provide various benefits like a noninvasive alternative for bone tissue engineering applications.

Keywords: injectable hydrogel, stem cell, osteogenic differentiation, tissue engineering

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Authors: Nick Weir, Robert Stevens, Alan Hargreaves, Martin McGinnity, Chris Tinsley

Abstract:

Hydrophobic materials have previously demonstrated the ability to elevate cell-cell interactions and promote the formation of neural networks whilst aligned nanofibers demonstrate the ability to induce extensive neurite outgrowth in an aligned manner. Hydrophobic materials typically elicit an immune response upon implantation and thus materials used for implantation are typically hydrophilic. Poly-L-lactic acid (PLLA) is a hydrophobic, non-immunogenic, FDA approved material that can be electrospun to form aligned nanofibers. Primary rat cortical neurons cultured for 10 days on aligned PLLA nanofibers formed 3D cell clusters, approximately 800 microns in diameter. Neurites that extended from these clusters were highly aligned due to the alignment of the nanofibers they were cultured upon and fasciculation was also evident. Plasma treatment of the PLLA nanofibers prior to seeding of cells significantly reduced the hydrophobicity and abolished the cluster formation and neurite fasciculation, whilst reducing the extent and directionality of neurite outgrowth; it is proposed that hydrophobicity induces the changes to cellular behaviors. Aligned PLLA nanofibers induced the formation of a structure that mimics the grey-white matter compartmentalization that is observed in vivo and thus represents a step forward in generating organoids or biomaterial-based implants. Upon implantation into the brain, the biomaterial architectures described here may provide a useful platform for both brain repair and brain remodeling initiatives.

Keywords: hydrophobicity, nanofibers, neurite fasciculation, neurite outgrowth, PLLA

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Authors: Yanwen Li, Shuguo Xie

Abstract:

In electromagnetic imaging, because of the diffraction limited system, the pixel values could change slowly near the edge of the image targets and they also change with the location in the same target. Using traditional digital image segmentation methods to segment electromagnetic gradient images could result in lots of errors because of this change in pixel values. To address this issue, this paper proposes a novel image segmentation and extraction algorithm based on Mean-Shift and dictionary learning. Firstly, the preliminary segmentation results from adaptive bandwidth Mean-Shift algorithm are expanded, merged and extracted. Then the overlap rate of the extracted image block is detected before determining a segmentation region with a single complete target. Last, the gradient edge of the extracted targets is recovered and reconstructed by using a dictionary-learning algorithm, while the final segmentation results are obtained which are very close to the gradient target in the original image. Both the experimental results and the simulated results show that the segmentation results are very accurate. The Dice coefficients are improved by 70% to 80% compared with the Mean-Shift only method.

Keywords: gradient image, segmentation and extract, mean-shift algorithm, dictionary iearning

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Authors: A. M. Malagon Escandon, J. A. Arenas Alatorre, C. P. Chaires Rosas, N. A. Vazquez Torres, B. Hernandez Tellez, G. Pinon Zarate, M. Herrera Enriquez, A. E. Castell Rodriguez

Abstract:

The current approach to the treatment of bone defects involves the use of scaffolds that provide a biological and mechanically stable niche to favor tissue repair. Despite the significant progress in the field of bone tissue engineering, several main problems associated are attributed to giving a low biodegradation degree, does not promote osseointegration and regeneration, if the bone is not healing as well as expected or fails to heal, will not be given a proper ossification or new bone formation. The actual approaches of bone tissue regeneration are directed to the use of decellularized native extracellular matrices, which are able of retain their own architecture, mechanic properties, biodegradability and promote new bone formation because they are capable of conserving proteins and other factors that are founded in physiological concentrations. Therefore, we propose an extracellular matrix-based bioscaffolds derived from bovine cancellous bone, which is processed by decellularization, demineralization, and hydrolysis of the collagen protein, these protocols have been successfully carried out in other organs and tissues; the effectiveness of its biosafety has also been previously evaluated in vivo and Food and Drug Administration (FDA) approved. In the specific case of bone, a more complex treatment is needed in comparison with other organs and tissues because is necessary demineralization and collagen denaturalization. The present work was made in order to obtain a temporal scaffold that succeed in degradation in an inversely proportional way to the synthesis of extracellular matrix and the maturation of the bone by the cells of the host.

Keywords: bioactive, biodegradable, bone, extracellular matrix-based bioscaffolds, stem cells, tissue engineering

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