Search results for: in vivo biocompatibility

Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe

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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.

Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects

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Authors: Laila Montaser, Hala Gabr, Maha El-Bassuony, Gehan Tawfeek

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Orthotropic liver transplantation (OLT) is the final procedure of both end stage and metabolic liver diseases. Hepatocyte transplantation is an alternative for OLT, but the sources of hepatocytes are limited. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into hepatocyte-like cells and are a potential alternative source for hepatocytes. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineages and, at least in vitro, have significant expansion capability. MSCs from bone marrow may have the potential to differentiate in vitro and in vivo into hepatocytes. Our study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from human bone marrow, are able to differentiate into functional hepatocyte-like cells in vitro. Our aim was to investigate the differentiation potential of BM-MSCs into hepatocyte-like cells. Adult stem cell therapy could solve the problem of degenerative disorders, including liver disease.

Keywords: bone marrow, differentiation, hepatocyte, stem cells

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li

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Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.

Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis

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Authors: Mukesh N. Kher, Anju P. Kunjadia, Dev S. Nauriyal, Chaitanya G. Joshi, Navin R. Sheth, Vaibhav D. Bhatt

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In-vivo immunotherapeutic potential on cytokines production and antibacterial activity of a topical herbal gel was evaluated in two breeds of cattle in bovine subclinical mastitis. The response to treatment was evaluated by enumerating somatic cell count (SCC), determining total bacterial count and studying the expression of different cytokines like (interleukin 6, 8, 12, GMCSF, interferon–γ and TNF‑α). The pre‑ and post‑treatment SCC in mastitic quarters did not differ statistically-significantly. However, total bacterial count declined significantly from day 0 onwards in both the breeds. Significant differences (P < 0.01) were observed in all types of cytokines production on day 0, 5, and 21 post last treatments in both the breeds. The comparison of cytokine expression profiles between crossbred and Gir cattle affirmed a significant difference in expression of IL-6 and TNF-α. The topical herbal gel showed immunomodulatory and antimicrobial activities in subclinical mastitis, and therefore the work supports its use as substitute herbal therapy against subclinical mastitis in bovines.

Keywords: antibacterial activity, immunomodulation, herbal gel, subclinical mastitis

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Authors: Faraz Zarghami, Elham Anari, Nosratollah Zarghami, Yones Pilehvar-Soltanahmadi, Abolfazl Akbarzadeh, Sepideh Jalilzadeh-Tabrizi

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The development of nanotherapy has presented a new method of drug delivery targeted directly to the neoplasmic tissues, to maximize the action with fewer dose requirements. In the past two decades, poly(lactic-co-glycolic acid) (PLGA) has frequently been investigated by many researchers and is a popular polymeric candidate, due to its biocompatibility and biodegradability, exhibition of a wide range of erosion times, tunable mechanical properties, and most notably, because it is a FDA-approved polymer. Chrysin is a natural flavonoid which has been reported to have some significant biological effects on the processes of chemical defense, nitrogen fixation, inflammation, and oxidation. However, the low solubility in water decreases its bioavailability and consequently disrupts the biomedical benefits. Being loaded with PLGA-PEG increases chrysin solubility and drug tolerance, and decreases the discordant effects of the drug. The well-structured chrysin efficiently accumulates in the breast cancer cell line (T47D). In the present study, the structure and chrysin loading were delineated using proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and the in vitro cytotoxicity of pure and nanochrysin was studied by the MTT assay. Next, the RNA was exploited and the cytotoxic effects of chrysin were studied by real-time PCR. In conclusion, the nanochrysin therapy developed is a novel method that could increase cytotoxicity to cancer cells without damaging the normal cells, and would be promising in breast cancer therapy.

Keywords: MTT assay, chrysin, flavonoids, nanotherapy

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Authors: Jayanthi Sivaraman

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Claudins are the important components of the tight junctions that play a key role in paracellular permeability. Among various members of Claudin family, Claudin 4 (CLDN4) is found to be overexpressed in ovarian, pancreatic carcinomas and other epithelial malignancies. Therefore, in this study, an attempt has been made to identify potent inhibitors for CLDN4 from the ZINC database using virtual screening, molecular docking and molecular dynamics simulations. A well refined molecular model of CLDN4 was built using Prime of Schrodinger v10.2(Template- PDB ID: 4P79). Approximately, 6 million compounds from ZINC database are subjected to high-throughput virtual screening (HTVS) against the active site of CLDN4. Molecular docking using GLIDE predicted ARG31, ASN142, ASP146 and ARG158 as critically important residues. Furthermore, three compounds from ZINC database (ZINC96331839, ZINC36533519 and ZINC75819394) showed highly promising ADME properties and binding affinity with stable conformation. The therapeutic efficiency of these lead compounds is evaluated and confirmed by in-vitro and in-vivo studies which leads to the development of novel anti-cancer drugs.

Keywords: ADME property, inhibitors, molecular docking, virtual screening

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Authors: Luo Guidong, Song Hang, Jim Song, Virginia Martin Torrejon

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Due to their excellent properties, polymer packaging foams have become increasingly essential in our current lifestyles. They are cost-effective and lightweight, with excellent mechanical and thermal insulation properties. However, they constitute a major environmental and health concern due to litter generation, ocean pollution, and microplastic contamination of the food chain. In recent years, considerable efforts have been made to develop more sustainable alternatives to conventional polymer packaging foams. As a result, biobased and compostable foams are increasingly becoming commercially available, such as starch-based loose-fill or PLA trays. However, there is still a need for bulk manufacturing of bio-foams planks for packaging applications as a viable alternative to their fossil fuel counterparts (i.e., polystyrene, polyethylene, and polyurethane). Gelatin is a promising biopolymer for packaging applications due to its biodegradability, availability, and biocompatibility, but its mechanical properties are poor compared to conventional plastics. However, as widely reported for other biopolymers, such as starch, the mechanical properties of gelatin-based bioplastics can be enhanced by formulation optimization, such as the incorporation of fibres from different crops, such as bamboo. This research aimed to produce gelatin-bamboo fibre foams by mechanical foaming and to study the effect of fibre content on the foams' properties and structure. As a result, foams with virtually no shrinkage, low density (<40 kg/m³), low thermal conductivity (<0.044 W/m•K), and mechanical properties comparable to conventional plastics were produced. Further work should focus on developing formulations suitable for the packaging of water-sensitive products and processing optimization, especially the reduction of the drying time.

Keywords: biobased and compostable foam, sustainable packaging, natural polymer hydrogel, cold chain packaging

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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Authors: Jyh-Ping Chen, Yu-Tin Lai

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Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

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Authors: Sunil Kamboj, Vipin Saini, Suman Bala, Gaurav Sharma

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The main aim of the present research was to encapsulate mefenamic acid in niosomes and incorporate the prepared niosomes in the carbopol gel base for sustained therapeutic action. Mefenamic acid loaded niosomes were prepared by thin film hydration technique and evaluated for entrapment efficiency, vesicular size and zeta potential. The entrapment efficiency of the prepared niosomes was found to increase with decreasing the HLB values of surfactants and vesicle size was found to increase with increasing the cholesterol concentration. Niosomal vesicles with good entrapment efficiencies were incorporated in carbopol gel base to form the niosomal gel. The prepared niosomal gel was evaluated for pH, viscosity, spreadability, extrudability and skin permeation study across the rat skin.The results of permeation study revealed that the gel formulated with span 60 niosomes sustained the drug release for 12 h. Further the in vivo study showed the good inhibition of inflammation by the gel prepared with span 60 niosomes.

Keywords: mefenamic acid, niosomal gel, nonionic surfactants, sustained release

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Authors: Pegah Ebrahimi, Farshad Oveissi, Iman Manavi-Tehrani, Sina Naficy, David F. Fletcher, Fariba Dehghani, David S. Winlaw

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Despite advances in modern surgery, congenital heart disease remains a medical challenge and a major cause of infant mortality. Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries in pulmonary valvar atresia. Current off-the-shelf options including human and adult products have limited biocompatibility and durability, and their fixed size necessitates multiple subsequent operations to upsize the conduit to match with patients’ growth over their lifetime. Non-physiological blood flow is another major problem, reducing the longevity of these prostheses. These limitations call for better designs that take into account the hemodynamical and anatomical characteristics of different patients. We have integrated tissue engineering techniques with modern medical imaging and image processing tools along with mathematical modeling to optimize the design of cardiovascular grafts in a patient-specific manner. Computational Fluid Dynamics (CFD) analysis is done according to models constructed from each individual patient’s data. This allows for improved geometrical design and achieving better hemodynamic performance. Tissue engineering strives to provide a material that grows with the patient and mimic the durability and elasticity of the native tissue. Simulations also give insight on the performance of the tissues produced in our lab and reduce the need for costly and time-consuming methods of evaluation of the grafts. We are also developing a methodology for the fabrication of the optimized designs.

Keywords: computational fluid dynamics, cardiovascular grafts, design optimization, tissue engineering

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Authors: A. Ojha, Y. K. Gupta

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Organophosphate (OP) pesticides are among the most widely used synthetic chemicals for controlling a wide variety of pests throughout the world. Chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) are among the most extensively used OP pesticides in India. DNA strand breaks and DNA-protein crosslinks (DPC) are toxic lesions associated with the mechanisms of toxicity of genotoxic compounds. In the present study, we have examined the potential of CPF, MPT, and MLT individually and in combination, to cause DNA strand breakage and DPC formation. Peripheral blood lymphocytes of rat were exposed to 1/4 and 1/10 LC50 dose of CPF, MPT, and MLT for 2, 4, 8, and 12h. The DNA strand break was measured by the comet assay and expressed as DNA damage index while DPC estimation was done by fluorescence emission. There was significantly marked increase in DNA damage and DNA-protein crosslink formation in time and dose dependent manner. It was also observed that MPT caused the highest level of DNA damage as compared to other studied OP compounds. Thus, from present study, we can conclude that studied pesticides have genotoxic potential. The pesticides mixture does not potentiate the toxicity of each other. Nonetheless, additional in vivo data are required before a definitive conclusion can be drawn regarding hazard prediction to humans.

Keywords: organophosphate, pesticides, DNA damage, DNA protein crosslink, genotoxic

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Authors: Warachate Khobjai, Suriyan Sukati, Khemjira Jarmkom, Pattaranut Eakwaropas, Surachai Techaoei

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The propose of this study was to investigate in vitro thrombolytic activity of Zingiber cassumunar Roxb. and Prasaplai, a Thai herbal formulation of Z. cassumunar Roxb. Herbs were extracted with boiling water and concentrated by lyophilization. To observe their thrombolytic potential, an in vitro clot lysis method was applied where streptokinase and sterile distilled water were used as positive and negative controls, respectively. Crude aqueous extracts from Z. cassumunar Roxb. and Prasaplai formula showed significant thrombolytic activity by clot lysis of 17.90% and 25.21%, respectively, compared to the negative control water (5.16%) while the standard streptokinase revealed 64.78% clot lysis. These findings suggest that Z. cassumunar Roxb. exhibits moderate thrombolytic activity and cloud play an important role in the thrombolytic properties of Prasaplai formula. However, further study should be done to observe in vivo clot dissolving potential and to isolate active component(s) of these extracts.

Keywords: thrombolytic activity, clot lysis, Zingiber cassumunar Roxb., Prasaplai formula, aqueous extract

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Authors: Abdelkarim Mahdhi, Fdhila Kais, Faouzi Lamari, Zeineb Hmila, Fathi Kamoun, Maria Ángeles Esteban, Amina Bakhrouf

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Pathogenic bacteria are considered to be responsible for several infectious diseases in aquaculture. To overcome diseases in fish culture, the use of antimicrobial drugs as strategy, have been adopted. The use of probiotic was a promising approach to avoid the risk associated to pathogenic bacteria. To find a biological control treatment against pathogens, we undertook this investigation to study the maintain of the probiotic properties of Bacillus sp., such as viability, adhesive ability to abiotic surface, antibacterial activity and pathogenicity/toxicity, under marine starvation conditions. Our data revealed that the tested strains maintained their capacity to inhibit pathogens in vivo and in vitro conditions. These strains maintain their adhesive capacity to polystyrene and do not demonstrate the pathogenic or toxic effect to the host. The obtained results give insight about the effect of starvation conditions on the physiological responses of these Bacillus strains that can be considered as a potential candidate’s probiotic.

Keywords: bacillus, probiotic, cell viability, starvation conditions

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Authors: Elham Vojoudi, Marzieh Mehrafza, Ahmad Hosseini, Azadeh Raofi, Maryam Najafi

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Premature ovarian failure (POF) has become one of the main causes of infertility in women of childbearing age and the incidence of this disorder is increasing year by year. In these patients, poor ovarian response (POR) to gonadotropins reflects a diminished ovarian reserve (DOR) that gives place to few follicles despite aggressive stimulation. Up to now, egg donation is the only way to resolve infertility problems in POF patients. Therefore, some novel aspects such as activating (Akt signaling pathway) and inhibiting (Hippo-signaling) elements have been identified as IVA procedure that promotes primordial follicle activation. In this study, we used the newly developed technique (combination of in vitro activation of dormant follicles (IVA) and stem cell therapy) to promote ovarian follicle growth much more efficiently than the natural, in vivo process for women with POF. Transplantation of Warton Jelly-MSCs to the ovaries of POF patients rescued overall ovarian function. Participants (10 patients) were followed up monthly for a period of six months by hormonal (AMH, FSH, LH and E2), clinical (resuming menstruation), and US (folliculometry) outcomes after a laparoscopic operation. In summary, IVA/WJ-MSC transplantation may provide an effective treatment for POF.

Keywords: POF, in vitro activation, stem cell therapy, infertility

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Authors: Yogita Patil-Sen

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Magnetic nanoparticles such as those made of iron oxide have been widely explored as biocatalysts, contrast agents, and drug delivery systems. However, some of the challenges associated with these particles are agglomeration and biocompatibility, which lead to concern of toxicity of the particles, especially for drug delivery applications. Coating the particles with biocompatible materials such as lipids and peptides have shown to improve the mentioned issues. Thus, these core-shell type nanoparticles are emerging as the new class of nanomaterials for targeted drug delivery applications. In this study, various types of core-shell magnetic nanoparticles are prepared and characterized using techniques, such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermogravimetric Analysis (TGA). The heating ability of nanoparticles is tested under oscillating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of oscillating field. The results suggest that the core-shell nanoparticles exhibit superparamagnetic behaviour, although, coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the oscillating magnetic field. Thus, the results strongly indicate the suitability of the prepared core-shell type nanoparticles as drug delivery vehicles and their potential in magnetic hyperthermia applications and for hyperthermia cancer therapy.

Keywords: core-shell, hyperthermia, magnetic nanoparticles, targeted drug delivery

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Authors: A. Banerjee, C. Grazon, B. Nadal, T. Pons, Y. Krishnan, B. Dubertret

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Quantum Dots (QDs) have emerged as novel fluorescent probes for biomedical applications. The photophysical properties of QDs such as broad absorption, narrow emission spectrum, reduced blinking, and enhanced photostability make them advantageous over organic fluorophores. However, for some biological applications, QDs need to be first targeted to specific intracellular locations. It parallel, base pairing properties and biocompatibility of DNA has been extensively used for biosensing, targetting and intracellular delivery of numerous bioactive agents. The combination of the photophysical properties of QDs and targettability of DNA has yielded fluorescent, stable and targetable nanosensors. QD-DNA conjugates have used in drug delivery, siRNA, intracellular pH sensing and several other applications; and continue to be an active area of research. In this project, a novel method to synthesise QD-DNA conjugates and their applications in bioimaging are investigated. QDs are first solubilized in water using a thiol based amphiphilic co-polymer and, then conjugated to amine functionalized DNA using a heterobifunctional linker. The conjugates are purified by size exclusion chromatography and characterized by UV-Vis absorption and fluorescence spectroscopy, electrophoresis and microscopy. Parameters that influence the conjugation yield such as reducing agents, the excess of salt and pH have been investigated in detail. In optimized reaction conditions, up to 12 single-stranded DNA (15 mer length) can be conjugated per QD. After conjugation, the QDs retain their colloidal stability and high quantum yield; and the DNA is available for hybridization. The reaction has also been successfully tested on QDs emitting different colors and on Gold nanoparticles and therefore highly generalizable. After extensive characterization and robust synthesis of QD-DNA conjugates in vitro, the physical properties of these conjugates in cellular milieu are being invistigated. Modification of QD surface with DNA appears to remarkably alter the fate of QD inside cells and can have potential implications in therapeutic applications.

Keywords: bioimaging, cellular targeting, drug delivery, photostability

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Authors: Jorge Prada, Christina Cordes, Carsten Harms, Walter Lang

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The development of microfluidic-based biosensors over the last years has shown an increasing employ of thermoplastic polymers as constitutive material. Their low-cost production, high replication fidelity, biocompatibility and optical-mechanical properties are sought after for the implementation of disposable albeit functional lab-on-chip solutions. Among the range of thermoplastic materials on use, the Cyclo-Olefin Copolymer (COC) stands out due to its optical transparency, which makes it a frequent choice as manufacturing material for fluorescence-based biosensors. Moreover, several processing techniques to complete a closed COC microfluidic biosensor have been discussed in the literature. The reported techniques differ however in their implementation, and therefore potentially add more or less complexity when using it in a mass production process. This work introduces and reports results on the application of a purely thermal bonding process between COC substrates, which were produced by the hot-embossing process, and COC foils containing screen-printed circuits. The proposed procedure takes advantage of the transition temperature difference between two COC grades foils to accomplish the sealing of the microfluidic channels. Patterned heat injection to the COC foil through the COC substrate is applied, resulting in consistent channel geometry uniformity. Measurements on bond strength and bursting pressure are shown, suggesting that this purely thermal bonding process potentially renders a technique which can be easily adapted into the thermoplastic microfluidic chip production workflow, while enables a low-cost as well as high-quality COC biosensor manufacturing process.

Keywords: biosensor, cyclo-olefin copolymer, hot embossing, thermal bonding, thermoplastics

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Authors: Muhammad Asim Nazir

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The investigations reported in this manuscript were carried on the screening of one hundred and seventy-eight chickpea germplasm lines/cultivars against wilt disease, caused by Fusarium oxysporum f. sp. ciceris. The screening was conducted in vivo (field) conditions. The field screening was accompanied with the study of some epidemiological factors affecting the occurrence and severity of the disease. Among the epidemiological factors maximum temperature range (28-40°C), minimum temperature range (12-24°C), relative humidity (19-44%), soil temperature (26-41°C) and soil moisture range (19-34°C) was studied for affecting the disease incidence/severity. The results revealed that air temperature was positively correlated with diseases. Soil temperature data revealed that in all cultivars disease incidence was maximum as 39°C. Most of the plants show 40-50% disease incidence. Disease incidence decreased at 33.5°C. The result of correlation of relative humidity of air and wilt incidence revealed that all cultivars/lines were negatively correlated with relative humidity. With increasing relative humidity wilt incidence decreased and vice versa.

Keywords: chickpea, epidemiological, screening, disease

Procedia PDF Downloads 641

Authors: Debajyoti Bose

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Chitosan has received much attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine. Chitosan is a positively charged natural biodegradable and biocompatible polymer. It is a linear polysaccharide consisting of β-1,4 linked monomers of glucosamine and N-acetylglucosamine. Chitosan can be mainly obtained from fungal sources during large fermentation process. In this study,three different fungal strains Aspergillus niger NCIM 1045, Aspergillus oryzae NCIM 645 and Mucor indicus MTCC 3318 were used for the production of chitosan. The growth mediums were optimized for maximum fungal production. The produced chitosan was characterized by determining degree of deacetylation. Chitosan possesses one reactive amino at the C-2 position of the glucosamine residue, and these amines confer important functional properties to chitosan which can be exploited for biofabrication to generate various chemically modified derivatives and explore their potential for pharmaceutical field. Chitosan nanoparticles were prepared by ionic cross-linking with tripolyphosphate (TPP). The major effect on encapsulation and release of protein (e.g. enzyme diastase) in chitosan-TPP nanoparticles was investigated in order to control the loading and release efficiency. It was noted that the chitosan loading and releasing efficiency as a nanocapsule, obtained from different fungal sources was almost near to initial enzyme activity(12026 U/ml) with a negligible loss. This signify, chitosan can be used as a polymeric drug as well as active component or protein carrier material in dosage by design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. Based upon these initial experiments, studies were also carried out on modification of chitosan based nanocapsules incorporated with physiologically important enzymes and nutraceuticals for target delivery.

Keywords: fungi, chitosan, enzyme, nanocapsule

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Authors: Deon Bezuidenhout

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Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.

Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft

Procedia PDF Downloads 296

Authors: Jacky Bhagat, Baban S Ingole

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In this study, in vivo experiments were carried out to investigate the effects of a toxic polycyclic aromatic hydrocarbon (PAH), benzo(k)fluoranthene (B[k]F), on marine gastropod, Morula granulata collected from Goa, west coast of India. Snails were exposed to different concentrations of B(k)F (1, 10, 25 and 50 µg/L) for 96 h. The genotoxic effects were evaluated by measuring DNA strand breaks using alkaline comet assay and oxidative stress were measured with the help of battery of biomarkers such as superoxide dismutase (SOD) catalase (CAT), glutathione-s-transferase (GST), and lipid peroxidation (LPO). Concentration-dependent increase in percentage tail DNA (TDNA) was observed in snails exposed to B(k)F. Exposure concentrations above 1 µg/L of B(k)F, showed significant increase in SOD activity and LPO value in snails. After 96 h, SOD activity were found to be doubled for 50 µg/L of B(k)F with reference to control. Significant increase in CAT and GST activity was observed at all exposure conditions at the end of the exposure time. Our study showed that B(k)F induces oxidative stress in snails which further lead to genotoxic damage.

Keywords: benzo(k)fluoranthene, comet assay, gastropod, oxidative stress

Procedia PDF Downloads 344

Authors: Aliaa M. S. Salem, Soliman I. El-Hout, Amira Gaber, Hassan Nageh

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Nowadays, the development of poisonous gas detectors is considered to be an urgent matter to secure human health and the environment from poisonous gases, in view of the fact that even a minimal amount of poisonous gas can be fatal. Of these concerns, various inorganic or organic sensing materials have been used. Among these are conducting polymers, have been used as the active material in the gassensorsdue to their low-cost,easy-controllable molding, good electrochemical properties including facile fabrication process, inherent physical properties, biocompatibility, and optical properties. Moreover, conducting polymer-based chemical sensors have an amazing advantage compared to the conventional one as structural diversity, facile functionalization, room temperature operation, and easy fabrication. However, the low selectivity and conductivity of conducting polymers motivated the doping of it with varied materials, especially graphene, to enhance the gas-sensing performance under ambient conditions. There were a number of approaches proposed for producing polymer/ graphene nanocomposites, including template-free self-assembly, hard physical template-guided synthesis, chemical, electrochemical, and electrospinning...etc. In this work, we aim to prepare a novel gas sensordepending on Electrospun nanofibers of conducting polymer/RGO composite that is the effective and efficient expectation of poisonous gases like ammonia, in different application areas such as environmental gas analysis, chemical-,automotive- and medical industries. Moreover, our ultimate objective is to maximize the sensing performance of the prepared sensor and to check its recovery properties.

Keywords: electro spinning process, conducting polymer, polyaniline, polypyrrole, polythiophene, graphene oxide, reduced graphene oxide, functionalized reduced graphene oxide, spin coating technique, gas sensors

Procedia PDF Downloads 186

Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

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Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

Procedia PDF Downloads 129

Authors: Jeremy J. Johnson

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Mediterranean herbs including rosemary (Rosmarinus officinalis) contain a variety of phytochemicals including diterpenes that possess extensive biological activity. Applications of diterpenes, including the more abundant forms carnosol and carnosic acid, have been shown to possess anti-cancer, anti-inflammatory, anti-oxidant, and anti-proliferation properties. To confirm these properties, we have evaluated rosemary extract and selected diterpenes for biological activity in cancer and inflammatory models. Our preliminary data have revealed that select diterpenes can disrupt androgen receptor functionality in prostate and breast cancer cells. This property is unique among natural products for hormone-responsive cancers. The second area of interest has been evaluating rosemary extract and selected diterpenes for activation of sestrin-2, an antioxidant protein, in colon cancer cells. A combination of in vitro and in vivo approaches have been utilized to characterize the activity of rosemary diterpenes in rosemary. Taken together, these results suggest that phytochemicals found in rosemary have distinct pharmacological actions for disrupting cell-signaling pathways in cancer and inflammatory bowel disease.

Keywords: rosemary, diterpene, cancer, inflammation

Procedia PDF Downloads 146

Authors: Muhammad Mohsan, Mehboob Ur-Rahman, Sana Zulfiqar, Shumila Ashfaq

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Brown Rust (Puccinia triticina), also known as leaf rust, pose a serious threat to wheat cultivation in the world. Nine candidate wheat lines/mutants were subjected to rust inoculation, lodging and aphid population in vivo conditions. Four lines/mutants (E-284, E-505, 2008-6 MR and 2008-14MR) were found resistant to leaf rust attack. Two lines (PGMB 15-29 and 2011-1 MR) displayed moderately resistant reactions against the disease. Three lines/mutants were depicted as susceptible to leaf rust. The lowest population of aphids, i.e., 16.67, was observed on 2008-14MR. Three lines/mutants (NN1-47, NN1-89 and PGMB 15-29) were found under zero level of lodging. The presence and absence of different leaf rust-resistant genes like Lr13, Lr34, Lr46 and Lr67 were assessed with the help of molecular markers. All the wheat lines/mutants were found loaded with leaf rust-resistant genes such as Lr13 and Lr 34, while Lr46 and Lr67 were found in 66% of wheat lines/mutants. The resistant source can be exploited in the breeding program to develop rust, aphid and lodging with race-nonspecific resistant wheat variety.

Keywords: wheat, leaf rust, lodging, aphid

Procedia PDF Downloads 88

Authors: Mohammed Auwal Ibrahim, Isa Yunusa, Nafisa Kabir, Shazali Ali Baba, Amina Muhammad Yushau, Suraj Suraj Ibrahim, Zaharaddeen Idris Bello, Suleiman Haruna Suleiman, Murtala Bindawa Isah

Abstract:

Background: Inhibition of intestinal maltase and sucrase prevents postprandial blood glucose excursions which are beneficial in ameliorating diabetes-associated complications. Objective: In this study, the inhibitory effects of fruit extracts of Parinari macrophylla, Detarium microcarpum, Ziziphus spina-christi, Z. mairei and Parkia biglobosa were investigated against intestinal maltase and sucrase. Methods: Rats were given co-administration of the fruit extracts with maltose or sucrose and blood glucose levels were measured at 0, 30, 90 and 120 min. Results: The glucose-time curves indicated that all the fruits had the most potent inhibitory effects on both maltase and sucrase within the first 30 min. The computed Area Under the Curves (AUC0-120)for all the fruits indicated more potent inhibitory effects against intestinal maltase than sucrase.The ED50 range for the fruits extract against maltase and sucrase were 647.15-1118.35 and 942.44-1851.94 mg/kg bw respectively. Conclusion: The data suggests that the fruits could prevent postprandial hyperglycemia via inhibition of intestinal maltase and sucrase.

Keywords: diabetes mellitus, fruits, α-glucosidases, maltase, sucrase

Procedia PDF Downloads 384

Authors: N. O. Muniz, F. A. Vechietti, L. Treccani, K. Rezwan, Luis Alberto dos Santos

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Developing new technologies in the manufacture of biomaterials is a major challenge for researchers in the tissue engineering area. Many in vitro and in vivo studies have revealed the significance of the porous structure of the biomaterials on the promotion of bone ingrowth. The use of Rapid Prototyping in the manufacture of ceramics in the biomedical area has increased in recent years and few studies are conducted on obtaining alumina pieces. The aim of this work was the study of alumina pieces obtained by 3D printing and uniaxial dry pressing (DP) in order to evaluate porosity achieved by this two different techniques. Also, the influence of the powder drying process was determined. The row alumina powders were drying by freeze drying and oven. Apparent porosity, apparent density, retraction after thermal treatment were evaluated. The porosity values obtained by DP, regardless of method of drying powders, were much lower than those obtained by RP as expected. And for the prototyped samples, the method of powder drying significantly influenced porosities, reached 48% for drying oven versus 65% for freeze-drying. Therefore, the method of 3D printing, using different powder drying, allows a better control over the porosity.

Keywords: rapid prototyping, freeze-drying, porosity, alumina

Procedia PDF Downloads 471