Search results for: biomaterial inflammation

Authors: Amina Ben Abla, Sylvie Changotade, Geraldine Rohman, Guilhem Boeuf, Cyrine Dridi, Ahmed Elmarjou, Florence Dufour, Didier Lutomski, Abdellatif Elm’semi

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Understanding cell adhesion and interaction with the extracellular matrix is essential for biomedical and biotechnological applications, including the development of biomaterials. In recent years, numerous biomaterials have emerged and were used in the field of tissue engineering. Nevertheless, the lack of interaction of biomaterials with cells still limits their bio-integration. Thus, the design of bioactive biomaterials to improve cell attachment and proliferation is of growing interest. In this study, bio-functionalized material was developed combining a synthetic polymer scaffold surface with selected domains of type III human fibronectin (FNIII-DOM) to promote cell adhesion and proliferation. Bioadhesive ligand includes cell-binding domains of human fibronectin, a major ECM protein that interacts with a variety of integrins cell-surface receptors, and ECM proteins through specific binding domains were engineered. FNIII-DOM was produced in bacterial system E. coli in 5L fermentor with a high yield level reaching 20mg/L. Bioactivity of the produced fragment was validated by studying cellular adhesion of human cells. The adsorption and immobilization of FNIII-DOM onto the polymer scaffold were evaluated in order to develop an innovative biomaterial.

Keywords: biomaterials, cellular adhesion, fibronectin, tissue engineering

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Authors: Parnaz Boodagh, Danila Vella, Antonio Damore, Laura Modica De Mohac, Sang-Ho Ye, Garret Coyan, Gaetano Burriesci, William Wagner, Federica Cosentino

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The use of cardiac patches is among the main therapeutic solution for cardiovascular diseases, a leading mortality cause in the world with an increasing trend, responsible of 19 millions deaths in 2020. Several classes of biomaterials serve that purpose, both of synthetic origin and biological derivation, and many bioengineered treatment alternatives were proposed to satisfy two main requirements, providing structural support and promoting tissue remodeling. The objective of this paper is to compare the mechanical properties and the characterization of four cardiac patches: the Adeka, PhotoFix, CorPatch, and CardioCel patches. In vitro and in vivo tests included: biaxial, uniaxial, ball burst, suture retention for mechanical characterization; 2D surface topography, 3D volume and microstructure, and histology assessments for structure characterization; in vitro test to evaluate platelet deposition, calcium deposition, and macrophage polarization; rat right ventricular outflow tract (RVOT) models at 8- and 16-week time points to characterize the patch-host interaction. Lastly, the four patches were used to produce four stented aortic valve prosthesis, subjected to hydrodynamic assessment as well as durability testing to verify compliance with the standard ISO.

Keywords: cardiac patch, cardiovascular disease, cardiac repair, blood contact biomaterial

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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Authors: H. K. G. K. D. K. Hapuhinna, R. D. Gunaratne, H. M. J. C. Pitawala

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Hydroxyapatite is a bioceramic which can be used for applications in orthopedics and dentistry due to its structural similarity with the mineral phase of mammalian bones and teeth. In this study, it was synthesized, chemically changing natural Eppawala chloroapatite mineral as a value-added product. Sol-gel approach and solid state sintering were used to synthesize products using diluted nitric acid, ethanol and calcium hydroxide under different conditions. Synthesized Eppawala hydroxyapatite powder was characterized using X-ray Fluorescence (XRF), X-ray Powder Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) in order to find out its composition, crystallinity, presence of functional groups, bonding type, surface morphology, microstructural features, and thermal dependence and stability, respectively. The XRD results reflected the formation of a hexagonal crystal structure of hydroxyapatite. Elementary composition and microstructural features of products were discussed based on the XRF and SEM results of the synthesized hydroxyapatite powder. TGA and DSC results of synthesized products showed high thermal stability and good material stability in nature. Also, FTIR spectroscopy results confirmed the formation of hydroxyapatite from apatite via the presence of hydroxyl groups. Those results coincided with the FTIR results of mammalian bones including human bones. The study concludes that there is a possibility of producing hydroxyapatite using commercially available Eppawala chloroapatite in Sri Lanka.

Keywords: dentistry, Eppawala chlorapatite, hydroxyapatite, orthopedics

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Authors: Udayakumar Vee, Franck Quero

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Zwitterionic polymers generally have been viewed as a new class of antimicrobial and non-fouling materials. They offer a broad versatility for chemical modification and hence great freedom for accurate molecular design, which bear an equimolar number of homogenously distributed anionic and cationic groups along their polymer chains. This study explores the effectiveness of the auxetic zwitterion carboxylate/sulfonate hydrogel in the diabetic-induced mouse model. A series of silver metal-doped auxetic zwitterion carboxylate/sulfonate/vinylaniline copolymer hydrogels is designed via a 3D printer. Zwitterion monomers have been characterized by FT-IR and NMR techniques. The effect of changing the monomers and different loading ratios of Ag over zwitterion on the final hydrogel materials' antimicrobial properties and biocompatibility will be investigated in detail. The synthesized auxetic hydrogel has been characterized using a wide range of techniques to help establish the relationship between molecular level and macroscopic properties of these materials, including mechanical and antibacterial and biocompatibility and wound healing ability. This work's comparative studies and results provide new insights and guide us in choosing a better auxetic structured material for a broad spectrum of wound healing applications in the animal model. We expect this approach to provide a versatile and robust platform for biomaterial design that could lead to promising treatments for wound healing applications.

Keywords: auxetic, zwitterion, carboxylate, sulfonate, polymer, wound healing

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Authors: Udayakumar Veerabagu, Franck Quero

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Zwitterion carboxylate and sulfonate polymers generally have been viewed as a new class of antimicrobial and non-fouling materials. They offer a broad versatility for chemical modification and hence great freedom for accurate molecular design, which bear an equimolar number of homogenously distributed anionic and cationic groups along their polymer chains. This study explores the effectiveness of the auxetic zwitterion carboxylate/sulfonate hydrogel in the diabetic-induced mouse model. A series of silver metal-doped auxetic zwitterion carboxylate/sulfonate/vinylaniline copolymer hydrogels is designed via a 3D printer. Zwitterion monomers have been characterized by FT-IR and NMR techniques. The effect of changing the monomers and different loading ratios of Ag over zwitterion on the final hydrogel materials' antimicrobial properties and biocompatibility will be investigated in detail. The synthesized auxetic hydrogel has been characterized using a wide range of techniques to help establish the relationship between molecular level and macroscopic properties of these materials, including mechanical and antibacterial and biocompatibility and wound healing ability. This work's comparative studies and results provide new insights and guide us in choosing a better auxetic structured material for a broad spectrum of wound healing applications in the animal model. We expect this approach to provide a versatile and robust platform for biomaterial design that could lead to promising treatments for wound healing applications.

Keywords: auxetic, zwitterion, carboxylate, sulfonate, polymer, wound healing

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Authors: Sara Mercedes Barroso Pinzón, Antonio Javier Sanchéz Herencia, Begoña Ferrari, Álvaro Jesús Castro

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The current need for durable implants and bone substitutes characterised by biocompatibility, bioactivity and mechanical properties, without immunological rejection, is a major challenge for scientists. Hydroxyapatite (HAp) has been considered for decades as an ideal biomaterial for bone regeneration due to its chemical and crystallographic similarity to the mineral structure bioapatites. However, the lack of trace elements in the hydroxyapatite structure gives it very low mechanical and biological properties. In this sense, the objective of the research is to address the synthesis of hydroxyapatite with Mg from phosphate rock from sedimentary deposits in the central-eastern region of Colombia, taking advantage of the release of the species contained as natural precursors of Ca, P and Mg. The minerals present were studied, fluorapatite as the mineral of interest associated with mineralogical species of magnesium carbonates and quartz. The chemical and mineralogical composition was determined by X-ray fluorescence (XRF) and X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX); as well as the evaluation of the surface physicochemical properties of zeta potential (PZC), with the aim of studying the surface behaviour of the microconstituents present in the phosphate rock and to elucidate the synergistic mechanism between the minerals and establish the optimum conditions for the wet concentration process. From the products obtained and characterised by XRD, XRF, SEM, FTIR, RAMAN, HAp-Mg biocomposite scaffolds are fabricated and the influence of Mg on the morphometric parameters, mechanical and biological properties of the designed materials is evaluated.

Keywords: phosphate rock, hydroxyapatite, magnesium, biomaterials

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Authors: Shweta Shriwas, Sumeet Dwivedi, Raghvendra Dubey

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Plumeria pudica Linn. Family Apocynaceae commonly known as Nag Chmapa is grown wildly in many parts of India. The plant is medium size shrub, grown up to height of 5-10 feet, evergreen with white flowers. In traditional system of medicine, the plant is widely used in the treatment of worms, infection, inflammation, etc. So, far no any systematic and documented study was done to revealed quality control parameters and pharmacological aspect of the selected plant species, therefore, the attempt was made in present investigation to reveal the same. The parameters such as Ash value, FOM, LOD, SI, etc. were studied using various coarsely dried plant materials of the species. Analgesic, anti-inflammatory, anthelmentic and anti-microbial activity of various extract was investigated and reported in present work.

Keywords: Plumeria pudica, quality control, pharmacology, parameters

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Shalini Singh, Sanjay K. Srivastava, Govind, Mukhtar. A. Khan, P. K. Singh

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Nanotechnology is revolutionizing the development of biosensors. Nanomaterials and nanofabrication technologies are increasingly being used to design novel biosensors. Sensitivity and other attributes of biosensors can be improved by using nanomaterials with unique chemical, physical, and mechanical properties in their construction. Silicon is a promising biomaterial that is non-toxic and biodegradable and can be exploited in chemical and biological sensing. Present study demonstrated the streptavidin–biotin interaction on silicon surfaces with different topographies such as flat and nanostructured silicon (nanowires) surfaces. Silicon nanowires with wide range of surface to volume ratio were prepared by electrochemical etching of silicon wafer. The large specific surface of silicon nanowires can be chemically modified to link different molecular probes (DNA strands, enzymes, proteins and so on), which recognize the target analytes, in order to enhance the selectivity and specificity of the sensor device. The interaction of streptavidin with biotin was carried out on 3-aminopropyltriethoxysilane (APTS) functionalized silicon surfaces. Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) studies have been performed to characterize the surface characteristics to ensure the protein attachment. Silicon nanowires showed the enhance protein attachment, as compared to flat silicon surface due to its large surface area and good molecular penetration to its surface. The methodology developed herein could be generalized to a wide range of protein-ligand interactions, since it is relatively easy to conjugate biotin with diverse biomolecules such as antibodies, enzymes, peptides, and nucleotides.

Keywords: FTIR, silicon nanowires, streptavidin-biotin, XPS

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Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

Procedia PDF Downloads 48

Authors: Milena Trevisan Pelegrino, Bruna De Araujo Lima, Mônica H. M. Do Nascimento, Christiane B. Lombello, Marcelo Brocchi, Amedea B. Seabra

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Nitric oxide (NO) is a small molecule involved in a wide range of physiological and pathophysiological processes, including vasodilatation, control of inflammatory pain, wound healing, and antibacterial activities. As NO is a free radical, the design of drugs that generates therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL) - chitosan (CS) hydrogel, in an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial and biocompatibility properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior, and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications, at physiological and skin temperatures. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL-1 of hydrogel, which correspondents to 1 mmol·L-1 of GSNO). Interesting, the concentration range in which the NO-releasing hydrogel demonstrated antibacterial effect was not found toxic to Vero mammalian cell. Thus, GSNO-PL/CS hydrogel is suitable biomaterial for topical NO delivery applications.

Keywords: antimicrobial, chitosan, biocompatibility, S-nitrosothiols

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Authors: Sharareh Sharifi

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In this study, the crude extracts of Virgularia gustavina were examined as antibacterial, antifungal and anti-inflammatory agent. To assess inflammation, Xylene was applied to the ear of mice. The mice of the experimental group were fed with doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg of lipid extract of chloroform and hexane as a separate group and then statistical analysis was performed on the results. Chloroform and hexane extracts of sea pen have strong anti-inflammatory effects even at low doses which is probably due to 54% arachidonic acid. Antibacterial and antifungal effects of hexane and chloroform extracts were measured with MIC and MBC methods and it is shown that chloroform extract has best activity against Staphylococcus aureus on 125 µg/ml doze in MIC method.

Keywords: sea pen (virgularia gustaviana), lipid extract, anti-inflammatory and anti-bacterial activities, fatty acid

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Authors: Abubakar Ahmed, Zainab Mohammed, Hadiza D. Nuhu, Hamisu Ibrahim

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Introduction: The plant Tacazzea apiculata Oliv (Periplocaceae) is widely distributed in tropical West Africa. It is claimed to have multiple uses in traditional medicine among which are its use to treat hemorrhoids, inflammations and cancers. Methods: Ethno-botanical survey through interview and using show-and-tell method of data collection were conducted among Hausa and Fulani tribes of northern Nigeria with the view to document useful information on the numerous claims by the local people on the plant. Results: The results revealed that the plant T. apiculata has relative popularity among the herbalist (38.2 %), nomads (14.8 %) and fishermen (16.0%). The most important uses of the plant in traditional medicine are inflammation (Fedelity level: 25.7 %) and Haemorrhoids (Fedelity level: 17.1 %) Conclusion: These results suggest the relevance of T. apiculata in traditional medicine and as a good candidate for drug Development.

Keywords: ethno-botany, periplocaceae, Tacazzea apiculata, traditional medicine

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Authors: Muhammad Yasir, Debarun Dutta, Mark Willcox

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Biomaterial-associated infections are a multi-billion dollar burden globally. Antimicrobial peptide-based coatings may be able to prevent such infections. The aim of this study was to investigate the mechanism of action surface bound peptides (AMPs) against Pseudomonas aeruginosa 6294. Melimine and Mel4 were covalently attached to glass coverslips using azido-benzoic acid. Attachment was confirmed using X-ray photoelectron spectroscopy. P. aeruginosa was allowed to attach to AMP-coated glass for up to 6 hours. The effect of the surface-bound AMPs on bacterial cell membranes was evaluated using the dyes DiSC3-(5), Sytox green, SYTO 9 and propidium iodide with fluorescence microscopy. Release of cytoplasmic materials ATP and DNA/RNA were determined in the surrounding fluid. The amount of cell death was estimated by agar plate counts. The AMPs were successfully covalently bound to the glass as demonstrated by increases in %nitrogen of 3.6% (melimine) and 2.3% (Mel4) compared to controls. Immobilized peptides disrupted the cytoplasmic membrane potential of P. aeruginosa within 10 min. This was followed by the release of ATP after 2 h. Membrane permeabilization started at 3 h of contact with glass coated AMPs. There was a significant number of bacteria (59% for melimine; 36% for Mel-4) with damaged membranes after 4 h of contact. At the 6 h time point, release of DNA occurred with melimine releasing 2 times the amount of DNA/RNA than Mel4 surfaces (p < 0.05). Surface bound AMPs were able to disrupt cell membranes with subsequent release of cytoplasmic materials, and ultimately resulting in bacterial death.

Keywords: biomaterials, immobilized antimicrobial peptides, P. aeruginosa, mode of action

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Authors: Recep Duzsoz, Elif Bilgir, Derya Yildirim, Ozlem Gormez

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Radicular cysts develop in the root apex of tooth that is devitalized. Cysts are pathologic lesions with an epithelial lining encapsulated by connective tissue. Radicular cysts originate from epithelial remnants of the periodontal ligament in the root apex as a result of inflammation. They are most commonly observed in the maxillary anterior region, among men and in the third decade of life. Radiographically, they are seen as ovoid radiolucent lesions surrounded by a thin radioopaque margin. In this case, series was carried out in 15 radicular cysts of the jaws diagnosed in individuals. The cysts were evaluated age, sex, and localization. 12 of the cysts were localized in the maxillae, 3 of them were localised in the mandible. The female/male ratio of the lesions was 1/2. In conclusion, we evaluated age, localization and sex distribution of radicular cysts in this study. The knowledge of the features of the jaw cysts is a basic aspect to achieve diagnosis, complications and proper treatment.

Keywords: radicular cyst, jaws, CBCT, treatment

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Authors: Derradji Chebli, Abdallah Bouguettoucha, Abdelbaki Reffas Khalil Guediri, Abdeltif Amrane

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The removal of Methyl Green dye (MG) from aqueous solutions using modified P-brutia cones (PBH and PBN), has been investigated work. The physical parameters such as pH, temperature, initial MG concentration, ionic strength are examined in batch experiments on the sorption of the dye. Adsorption removal of MG was conducted at natural pH 4.5 because the dye is only stable in the range of pH 3.8 to 5. It was observed in experiments that the P-brutia cones treated with NaOH (PBN) exhibited high affinity and adsorption capacity compared to the MG P-brutia cones treated with HCl (PBH) and biosorption capacity of modified P-brutia cones (PBN and PBH) was enhanced by increasing the temperature. This is confirmed by the thermodynamic parameters (ΔG° and ΔH°) which show that the adsorption of MG was spontaneous and endothermic in nature. The positive values of ΔS° suggested an irregular increase in the randomness for both adsorbent (PBN and PBH) during the adsorption process. The kinetic model pseudo-first order, pseudo-second order, and intraparticle diffusion coefficient were examined to analyze the sorption process; they showed that the pseudo-second-order model is the one that best describes the adsorption process (MG) on PBN and PBH with a correlation coefficient R²> 0.999. The ionic strength has shown that it has a negative impact on the adsorption of MG on two supports. A reduction of 68.5% of the adsorption capacity for a value Ce=30 mg/L was found for the PBH, while the PBN did not show a significant influence of the ionic strength on adsorption especially in the presence of NaCl. Among the tested isotherm models, the Langmuir isotherm was found to be the most relevant to describe MG sorption onto modified P-brutia cones with a correlation factor R²>0.999. The capacity adsorption of P-brutia cones, was confirmed for the removal of a dye, MG, from aqueous solution. We note also that P-brutia cones is a material very available in the forest and low-cost biomaterial

Keywords: adsorption, p-brutia cones, forest wastes, dyes, isotherm

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Authors: Wan-Ting Shen, Ching-Liang Hsieh, Yi-Wen Lin

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Electroacupuncture (EA) has been reported effective for many kinds of pain and is a common treatment for acute or chronic pain. However, to date, there are limited studies examining the effect of acupuncture dosage. In our experiment, after injecting mice with Complete Freund’s Adjuvant (CFA) to induce inflammatory pain, two groups of mice were administered two different 15 min EA treatments at 2Hz. The first group received EA at a single acupuncture point (ST36, Zusanli) in both legs (two points), whereas the second group received two acupuncture points in both legs (four points) and the analgesic effect was compared. It was found that double points (ST36, Zusanli and SP6, Sanyinjiao) were significantly superior to single points (ST36, Zusanli) when evaluated using the electronic von Frey Test (mechanic) and Hargreaves’ Test (thermal). Through this study, it is expected more novel physiological mechanisms of acupuncture analgesia will be discovered.

Keywords: anti-inflammation, dose effect, electroacupuncture, pain control

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Authors: Manav Sabharwal, Ruda Rai Md, Candace Parker, James Ridley

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Wheat is one of the most commonly consumed grains worldwide, which contains gluten. Nowadays, gluten intake is considered to be a trigger for GRDs, including Celiac disease (CD), a common genetic disease affecting 1% of the US population, non-celiac gluten sensitivity (NCGS) and wheat allergy. NCGS is being recognized as an acquired gluten-sensitive enteropathy that is prevalent across age, ethnic and geographic groups. The cause of this entity is not fully understood, and recent studies suggest that it is more common in participants with irritable bowel syndrome (IBS), with iron deficiency anemia, symptoms of fatigue, and has considerable overlap in symptoms with IBS and Crohn’s disease. However, these studies were lacking in availability of complete serologies, imaging tests and/or pan-endoscopy. We performed a prospective study of 745 adult patients who presented to an outpatient clinic for evaluation of chronic upper gastro-intestinal symptoms and subsequently underwent an upper endoscopic (EGD) examination as standard of care. Evaluation comprised of comprehensive celiac antibody panel, inflammatory bowel disease (IBD) serologic markers, duodenal biopsies and Small Bowel Video Capsule Endoscopy (VCE), when available. At least 6 biopsy specimens were obtained from the duodenum and proximal jejunum during EGD, and CD3+ Intraepithelial lymphocytes (IELs) and villous architecture were evaluated by a single experienced pathologist, and VCE was performed by a single experienced gastroenterologist. Of the 745 patients undergoing EGD, 12% (93/745) patients showed elevated CD3+ IELs in the duodenal biopsies. 52% (387/745) completed a comprehensive CD panel and 7.2% (28/387) were positive for at least 1 CD antibody (Tissue transglutaminase (tTG), being the most common antibody in 65% (18/28)). Of these patients, 18% (5/28) showed increased duodenal CD3+ IELs, but 0% showed villous blunting or distortion to meet criteria for CD. Surprisingly, 43% (12/28) were positive for at 1 IBD serology (ASCA, ANCA or expanded IBD panel (LabCorp)). Of these 28 patients, 29% (8/28) underwent a SB VCE, of which 100 % (8/8) showed significant jejuno-ileal mucosal lesions diagnostic for IBD. Findings of abnormal CD antibodies (7.2%, 28/387) and increased CD3+ IELs on duodenal biopsy (12%, 93/745) were observed frequently in patients with UGI symptoms undergoing EGD in an outpatient clinic. None met criteria for CD, and a high proportion (43%, 12/28) showed evidence of overlap with IBD. This suggests a potential causal link of acquired GRDs to underlying inflammation and gut mucosal barrier disruption. Further studies to investigate a role for abnormal antigen presentation of dietary gluten to gut associated lymphoid tissue as a cause are justified. This may explain a high prevalence of GRDs in the population and correlation with IBS, IBD and other gut inflammatory disorders.

Keywords: celiac, gluten sensitive enteropathy, lymphocitic enteritis, IBS, IBD

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Authors: Kennedy Zinn, Chris Anderson

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Chronic Covid syndrome (CCS) is a condition in which individuals who test positive for Covid-19 experience persistent symptoms after recovering from the virus. CCS affects every organ system, including the central nervous system. Neurological “long-haul” symptoms last from a few weeks to several months and include brain fog, chronic fatigue, dyspnea, mood dysregulation, and headaches. Data suggest that 10-30% of individuals testing positive for Covid-19 develop CCS. Current literature indicates a decreased quality of life in persistent symptoms. CCS is a pervasive and pernicious COVID-19 sequelae. More research is needed to understand risk factors, impact, and possible interventions. Research frequently cites cytokine storming as noteworthy etiology in CCS. Cytokine storming is a malfunctional immune response and facilitates multidimensional interconnected physiological responses. The most prominent responses include abnormal blood flow, hypoxia/hypoxemia, inflammation, and endothelial damage. Neurological impairments and pathogenesis in CCS parallel that of traumatic brain injury (TBI). Both exhibit impairments in memory, cognition, mood, sustained attention, and chronic fatigue. Evidence suggests abnormal blood flow, inflammation, and hypoxemia as shared causal factors. Cytokine storming is also typical in mTBI. The shared characteristics in symptoms and etiology suggest potential parallel routes of investigation that allow for better understanding of CCS. Research on the effect of altitude in mTBI varies. Literature finds decreased rates of concussions at higher altitudes. Other studies suggest that at a higher altitude, pre-existing mTBI symptoms are exacerbated. This may mean that in CCS, the geographical location where individuals live and the location where individuals experienced acute Covid-19 symptoms may influence the severity and risk of developing CCS. It also suggests that clinics which treat mTBI patients could also provide benefits for those with CCS. This study aims to examine the relationships between altitude and CCS as a risk factor and investigate the longevity and severity of symptoms in different altitudes. Existing patient data from a concussion clinic using fMRI scans and self-reported symptoms will be used for approximately 30 individuals with CCS symptoms. The association between acclimated altitude and CCS severity will be analyzed. Patients will be classified into low, medium, and high altitude groups and compared for differences on fMRI severity scores and self-reported measures. It is anticipated that individuals living in lower altitudes are at higher risk of developing more severe neuropsychological symptoms in CCS. It is also anticipated that a treatment approach for mTBI will also be beneficial to those with CCS.

Keywords: altitude, chronic covid syndrome, concussion, covid brain, EPIC treatment, fMRI, traumatic brain injury

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Authors: Fakhrosadat Sajjadian

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In the USA, about 5% of women diagnosed with breast cancer annually are affected by Inflammatory Breast Cancer (IBC), which is a highly aggressive type of Locally Advanced Breast Cancer (LABC). It is a type of LABC that is clinically and pathologically different, known for its rapid growth, invasiveness, and ability to promote the growth of blood vessels. Almost all women are found to have lymph nodes affected upon diagnosis, while around 36% show obvious distant metastases. Even with the latest improvements in multimodality therapies, the outlook for patients with IBC remains bleak, as the average disease-free survival time is less than 2.5 years. Recent research on the genetic factors responsible for the IBC phenotype has resulted in the discovery of genes that play a role in the advancement of this illness. The development of primary human cell lines and animal models has assisted in this research. These advancements offer new possibilities for future actions in identifying and treating IBC.

Keywords: breast cancer, inflammation, diagnosis, IBC, LABC

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Authors: Meltem Koray, Arda Ozgon, Duygu Ofluoglu, Mehmet Yaltirik

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Oral ulcerations can be seen as a side effect of different drugs. These ulcers usually appear within a few weeks following drug treatment. In most of cases, these ulcers resist to conventional treatments, such as anesthetics, antiseptics, anti-inflammatory agents, cauterization, topical tetracycline and corticosteroid treatment. The diagnosis is usually difficult, especially in patients receiving multiple drug therapies. Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing and also used for oral ulcer treatment. The aim of this report is to present the treatment of drug-induced oral ulceration on maxillary mucosa with HA gel. 60-year-old male patient was referred to Department of Oral and Maxillofacial Surgery complaining of oral ulcerations during few weeks. He had received chemotherapy and radiotherapy in 2014 with the diagnosis of nasopharyngeal carcinoma, and he has accompanying systemic diseases such as; cardiological, neurological diseases and gout. He is medicated with Escitalopram (Cipralex® 20mg), Quetiapine (Seroquel® 100mg), Mirtazapine (Zestat® 15mg), Acetylsalicylic acid (Coraspin® 100mg), Ramipril-hydrochlorothiazide (Delix® 2.5mg), Theophylline anhydrous (Teokap Sr® 200mg), Colchicine (Colchicum Dispert® 0.5mg), Spironolactone (Aldactone® 100mg), Levothyroxine sodium (Levotiron® 50mg). He had painful oral ulceration on the right side of maxillary mucosa. The diagnosis was 'drug-induced oral ulceration' and HA oral gel (Aftamed® Oral gel) was prescribed 3 times a day for 2 weeks. Complete healing was achieved within 3 weeks without any side effect and discomfort. We suggest that HA oral gel is a potentially useful local drug which can be an alternative for management of drug-induced oral ulcerations.

Keywords: drug-induced, hyaluronic acid, oral ulceration, maxillary mucosa

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Authors: Alireza Barari, Ahmad Abdi

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Introduction: Plyometric training (PT) is popular among individuals involved in dynamic sports, and is executed with a goal to improve muscular performance. Cytokines are considered as immunoregulatory molecules for regulation of immune function and other body responses. In addition, the pro-inflammatory cytokines, TNF-α andIL-1β, have been reported to be increased during and after exercises. If some of the cytokines which cause responses such as inflammation of cells in skeletal muscles, with manipulating of training program or optimizing nutrition, it can be avoided or limited from those injuries caused by cytokines release. Its shows that mistletoe extracts show immune-modulating effects. Materials and methods: present study was to investigate the effect of six weeks PT with or without mistletoe supplementation (MS)(10 mg/kg) on cytokine responses and performance in male basketball players. This study is semi-experimental. Statistic society of this study was basketball player’s male students of Mahmoud Abad city. Statistic samples are concluded of 32 basketball players with an age range of 14–17 years was selected from randomly. Selection of samples in four groups of 8 individuals Participants were randomly assigned to either an experimental group (E, n=16) that performed plyometric exercises with (n=8) or without (n=8) MS, or a control group that rested (C, n=16) with (n=8) or without (n=8) MS. Plants were collected in June from the Mazandaran forest in north of Iran. Then they dried in exposure to air without any exposition to sunlight, on a clean textile. For better drying the plants were high and down until they lost their water. Each subject consumed 10 mg/kg/day of extract for six weeks of intervention. Pre and post-testing was performed in the afternoon of the same day. Blood samples (10 ml) were collected from the intermediate cubital vein of the subjects. Serum concentration of IL-1β and TNF-α were measured by ELISA method. Data analysis was performed using pretest to posttest changes that assessed by t-test for paired samples. After the last plyometric training program, the second blood samples were in the next day. Group differences at baseline were evaluated using One-way ANOVA (post-hock Tukey) test is used for analysis and comparison of three group’s variables. Results: PT with or without MS improved the one repetition maximum leg and chest press, Sargeant test and power in RAST (P < 0.05). However there were no statistically significant differences between groups in Vo2max measures (P > 0.05). PT resulted in a significant increase in plasma IL-1β concentration from 1.08±0.4 mg/ml in pre-training to 1.68±0.18 mg/ml in post-training (P=0.006). While the MS significantly decreased the training-induced increment of IL-1β (P=0.007). In contrast, neither PT nor MS had any effect on TNF-α levels (P > 0.05). Discussion: The results of this investigation indicate that PT improved muscular performance and increases the IL-1β concentration. Increasing of IL-1β after exercise in damaged skeletal muscle has shown of the role of this cytokine in inflammation processes and damaged skeletal muscle repair. However mistletoe supplementation ameliorates the increment of IL-1β levels, indicating the beneficial effect of mistletoe on immune response following plyometric training.

Keywords: mistletoe supplementation, training, IL-1β, TNF-α

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Authors: Mehieddine Bouatrous

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Recently bioactive ceramic materials have been applied in the biomedical field as bulk, granular, or coating materials for more than half a century. More recently, bone tissue engineering scaffolds made of highly porous bioactive ceramic, glass-ceramic, and composite materials have also been created. As a result, recent bioactive ceramic structures have a high bioactivity rate, an open pores network, and good mechanical characteristics simulating cortical bone. Cyclowollastonite frameworks are also suggested for use as a graft material. As a porogenous agent, various amounts of the polymethyl methacrylate (PMMA) powders were used in this study successfully to synthesize a highly interrelated, nanostructured porous cyclowollastonite with a large specific surface area where the morphology and porosity were investigated. Porous cyclowollastonite bioactive ceramics were synthesized with a cost-effective and eco-friendly wet chemical method. The synthesized biomaterial is bioactive according to in vitro tests and can be used for bone tissue engineering scaffolds where cyclowollastonite sintered dense discs were submerged in simulated body fluid (S.B.F.) for various periods of time (1-4 weeks), resulting in the formation of a dense and consistent layer of hydroxyapatite on the surface of the ceramics, indicating its good in vitro bioactivity. Therefore, the cyclowollastonite framework exhibits good in vitro bioactivity due to its highly interconnecting porous structure and open macropores. The results demonstrate that even after soaking for several days, the surface of cyclowollastonite ceramic can generate a dense and consistent layer of hydroxyapatite. The results showed that cyclowollastonite framework exhibits good in vitro bioactivity due to highly interconnecting porous structure and open macropores.

Keywords: porous, bioactive, biomaterials, S.B.F, cyclowollastonite, biodegradability

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Authors: Luksanaporn Krungkraipetch

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Epidemic keratoconjunctivitis is an acute infection caused by the adenovirus symptoms of eye irritation, tearing an incubation period of 7-9 days from the respiratory tract into the eye and often cohesion in the community who work in the school's pool as well as a shopping mall. After infection can cause symptoms within 1-2 days chance to infect others up to two weeks. In some cases when red-eye better they had potential complications of the eye, inflammation occurs 7-10 days after conjunctivitis. It could be for several more months to recover. This study is a cross-sectional study with one hundred and eleven beach venders, and purpose of the research was to assess the knowledge, that knowledge has improved much. By comparing before and after the knowledge of the use of questionnaires and test your knowledge. The statistics used for data analysis percent, arithmetic mean and T-test. The statistics used to analyze data at the level of statistical p ≤ 0.05. Result of this study; mostly female (83.8%), most age 19-35 years (42.3%). Hometown is mostly in Chonburi 74.8%. 20.7% had epidemic keratoconjunctivitis within one year. Compared between before and after gave knowledge; after gave knowledge is better than before gave knowledge p=0.00.

Keywords: knowledge, epidemic keratoconjunctivitis, conjunctivitis, beach vender

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Authors: Alireza Arab, Morteza Elsa, Amirhossein Moghanian

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In this study, experiments were carried out to achieve a promising multifunctional and modified silicate based bioactive glass (BG). The main aim of the study was investigating the effect of lithium (Li) and magnesium (Mg) substitution, on in vitro bioactivity of substituted-58S BG. Moreover, it is noteworthy to state that modified BGs were synthesized in 60SiO₂–(36-x)CaO–4P₂O₅–(x)Li₂O and 60SiO₂–(36-x)CaO–4P₂O₅–(x)MgO (where x = 0, 5, 10 mol.%) quaternary systems, by sol-gel method. Their performance was investigated through different aspects such as biocompatibility, antibacterial activity as well as their effect on alkaline phosphatase (ALP) activity, and proliferation of MC3T3 cells. The antibacterial efficiency was evaluated against methicillin-resistant Staphylococcus aureus bacteria. To do so, CaO was substituted with Li₂O and MgO up to 10 mol % in 58S-BGs and then samples were immersed in simulated body fluid up to 14 days and then, characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry, and scanning electron microscopy. Results indicated that this modification led to a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium revealed further pronounced effect. The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and ALP analysis illustrated that substitutions of both Li₂O and MgO, up to 5 mol %, had increasing effect on biocompatibility and stimulating proliferation of the pre-osteoblast MC3T3 cells in comparison to the control specimen. Regarding to bactericidal efficiency, the substitution of either Li or Mg for Ca in the 58s BG composition led to statistically significant difference in antibacterial behaviors of substituted-BGs. Meanwhile, the sample containing 5 mol % CaO/Li₂O substitution (BG-5L) was selected as a multifunctional biomaterial in bone repair/regeneration due to the improved biocompatibility, enhanced ALP activity and antibacterial efficiency among all of the synthesized L-BGs and M-BGs.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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Authors: Arunporn Itharat, Srisopa Ruangnoo, Pakakrong Thongdeeying

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The rhizomes of Dioscorea membranacea (DM) has long been used in Thai Traditional medicine to treat cancer and inflammatory conditions such as rheumatism. The objective of this study was to investigate anti-inflammatory activity by determining the inhibitory effect on LPS-induced TNF-α from RAW264.7 cells of crude extracts and pure isolated compounds from DM. Three known dihydrophenantrene compounds were isolated by a bioassay guided isolation method from DM ethanolic extract [2,4 dimethoxy-5,6-dihydroxy-9,10-dihydrophenanthrene (1) and 5-hydroxy-2,4,6-trimethoxy-9,10-dihydrophenanthrene(2) and 5,6,2 -trihydroxy 3,4-methoxy, 9,10- dihydrophenanthrene (3)]. 1 showed the highest inhibitory effect on PGE2, followed by 3 and 1 (IC50 = 2.26, 4.97 and >20 μg/ml or 8.31,17.25 and > 20 µM respectively). These findings suggest that this plant showed anti-inflamatory effects by displaying an inhibitory effect on TNF-α release, hence, this result supports the usage of Thai traditional medicine to treat inflammation related diseases.

Keywords: Dioscorea membranacea, anti-inflammatory activity, TNF-Alpha , dihidrophenantrene compound

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Authors: Isam A. H. Al Zubaidy

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A quick process may be needed to get the benefit the big generated quantity of waste oil sludge (WOS). The process includes the mixing process of WOS with commercial diesel fuel. Different ratios of WOS to diesel fuel were prepared ranging 1:1 to 20:1 by mass. The mixture was continuously mixing for 10 minutes using bench type overhead stirrer and followed by filtration process to separate the soil waste from filtrate oil product. The quantity and the physical properties of the oil filtrate were measured. It was found that the addition of up to 15% WOS to diesel fuel was accepted without dramatic changes to the properties of diesel fuel. The amount of waste oil sludge was decreased by about 60% by mass. This means that about 60 % of the mass of sludge was recovered as light fuel oil. The physical properties of the resulting fuel from 10% sludge mixing ratio showed that the specific gravity, ash content, carbon residue, asphaltene content, viscosity, diesel index, cetane number, and calorific value were affected slightly. The color was changed to light black color. The sulfur content was increased also. This requires other processes to reduce the sulfur content of the resulting light fuel. A new desulfurization process was achieved using adsorption techniques with activated biomaterial to reduce the sulfur content to acceptable limits. Adsorption process by ZnCl₂ activated date palm kernel powder was effective for improvement of the physical properties of diesel like fuel. The final sulfur content was increased to 0.185 wt%. This diesel like fuel can be used in all tractors, buses, tracks inside and outside the refineries. The solid remaining seems to be smooth and can be mixed with asphalt mixture for asphalting the roads or can be used with other materials as an asphalt coating material for constructed buildings. Through this process, valuable fuel has been recovered, and the amount of waste material had decreased.

Keywords: oil sludge, diesel fuel, blending process, filtration process

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Authors: Aroonsri Priprem, Sucharat Limsitthichaikoon, Suttasinee Thappasarapong

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Anthocyanins are natural pigments with effective UV protection but their topical use could be limited due to their physicochemical characteristics. An attempt to overcome such limitations by complexation of 2 major anthocyanin-rich sources, C. ternatea, and Z. mays, for investigation on potential use as topical anti-inflammatory. Cell studies indicate no cytotoxicity of the anthocyanin complex (AC) up to 1 mg/ml tested in HaCaT and human forehead fibroblasts by MTT. Croton oil-induced ear edema in Wistar rats suggests an effective dose of 5 mg/cm2 of AC as a topical anti-inflammatory in comparison to 0.5 mg/cm2 of fluocinolone acetonide. Niosomal encapsulation of the AC significantly prolonged the anti-inflammatory activity particularly at 8 h after topical application (p = 0.0001). The AC was not cytotoxic and its anti-inflammatory and activity was dose-dependent and prolonged by niosomal encapsulation. It has also shown to promote collagen type 1 production in cell culture. Thus, AC could be a potential candidate for topical anti-inflammatory agent from natural resources.

Keywords: anthocyanin complex, ear edema, inflammation, niosomes, skin

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Authors: Kitti Supchukun, Kris Angkanaporn, Teerapong Yata

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The product innovation using a nutraceutical delivery system on improving the growth performance of broilers is the product planning and development to solve the antibiotics banning policy incurred in the local and global livestock production system. Restricting the use of antibiotics can reduce the quality of chicken meat and increase pathogenic bacterial contamination. Although other alternatives were used to replace antibiotics, the efficacy was inconsistent, reflecting on low chicken growth performance and contaminated products. The product innovation aims to effectively deliver the selected active ingredients into the body. This product is tested on the pharmaceutical lab scale and on the farm-scale for market feasibility in order to create product innovation using the nutraceutical delivery system model. The model establishes the product standardization and traceable quality control process for farmers. The study is performed using mixed methods. Starting with a qualitative method to find the farmers' (consumers) demands and the product standard, then the researcher used the quantitative research method to develop and conclude the findings regarding the acceptance of the technology and product performance. The survey has been sent to different organizations by random sampling among the entrepreneur’s population including integrated broiler farm, broiler farm, and other related organizations. The mixed-method results, both qualitative and quantitative, verify the user and lead users' demands since they provide information about the industry standard, technology preference, developing the right product according to the market, and solutions for the industry problems. The product innovation selected nutraceutical ingredients that can solve the following problems in livestock; bactericidal, anti-inflammation, gut health, antioxidant. The combinations of the selected nutraceutical and nanostructured lipid carriers (NLC) technology aim to improve chemical and pharmaceutical components by changing the structure of active ingredients into nanoparticle, which will be released in the targeted location with accurate concentration. The active ingredients in nanoparticle form are more stable, elicit antibacterial activity against pathogenic Salmonella spp and E.coli, balance gut health, have antioxidant and anti-inflammation activity. The experiment results have proven that the nutraceuticals have an antioxidant and antibacterial activity which also increases the average daily gain (ADG), reduces feed conversion ratio (FCR). The results also show a significant impact on the higher European Performance Index that can increase the farmers' profit when exporting. The product innovation will be tested in technology acceptance management methods from farmers and industry. The production of broiler and commercialization analyses are useful to reduce the importation of animal supplements. Most importantly, product innovation is protected by intellectual property.

Keywords: nutraceutical, nano structure lipid carrier, anti-microbial drug resistance, broiler, Salmonella

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