Search results for: heterochiral collagen scaffold

Authors: Faris M. Altaf, Abdullah M Elkeshy

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Forty-two albino male rats aged between 30 and 40 days (weighted 200 g to 250 g) were used in the present study. The left sural nerves of 36 rats were subjected to crush injury at 1 to 6 weeks intervals using 6 animals at each interval. The right and left sural nerves of the rest 6 rats were used as a control. After 2 weeks of the crush injury, the endoneurium showed channel-like spaces that were lined by the fibroblast-like cells and collagen bundles. These channels contained degenerated myelin and were connected with the perivascular and subperineurial spaces. Some of the flattened fibroblast-like cells were arranged in several layers in the subperineurial and perivascular spaces, forming barrier-like cellular sheets localizing the endoneurial edema in these spaces. Fibroblast-like cells also wrapped the regenerating nerve fibers by their branching cytoplasmic processes. At the end of the third week, the flattened fibroblasts formed nearly continuous sheets in the subperineurial and perivascular spaces. Macrophages were frequently noticed between these cellular barrier-like sheets and in the subperineurial and perivascular spaces. Conclusion: it could be concluded that the endoneurial fibroblast-like cells form barrier-like cellular sheets that localized the endoneurial edema in the subperineurial and perivascular spaces and create also the endoneurial channel-like spaces containing degenerated myelin and endoneurial edema helping the resolution of such edema.

Keywords: sural nerve, endoneurial fibroblast-like cells, endoneurial edema, barrier-like and channel-like spaces

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Authors: Yong Cang

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RJV001 is a subcutaneous injection containing mutated recombinant Collagenase H (ColH), leading to disruption of collagen matrix in adipose tissue and programmed cell death of adipocytes. Here we reported our clinical investigation of the safety, tolerance and pharmacodynamics of localized RJV001 injection into healthy human abdominal fat tissues (NCT04821648, Arizona Research Center). Investigate the safety, tolerance and clinical pharmacodynamics of subcutaneous RJV001 in humans. In the dose-escalating study, 18 subjects completed the study, 100% female, 78% white, with a mean age of 42[±9.9]. All three tested dose (0.05, 0.075 and 0.15 mg/injection), up to 30 injections, were safe and well-tolerated. Bruising and tenderness to palpation, mild to moderate, were the most frequent local skin reactions but nearly all resolved within 30 days. Additionally, physician-monitored ultrasound measurement showed that a reduction in abdominal fat tissue thickness was consistently observed in Cohort C (0.075, 0.15 mg/injection, 30injections), with a mean reduction of 7.37 [± 2.020] mm. Based on this clinical study, RJV001 has been advanced to phase II clinical studies. In the dose-escalating study, subcutaneously administered RJV001 was safe and well-tolerated in healthy adults up to 0.15 mg/injection, 30 injections. Fat reduction and adipocytolysis were observed by ultrasound measurements and histological analysis for exploratory purposes.

Keywords: fat reduction, mutant collagenase, clinical trial, subcutaneous injection

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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: Abderrahim Cheriguene, Fatiha Arioui

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The experimental study focuses on the extraction of pectin, whey protein and gelatin, and the study of their functional properties. Microbiological, physicochemical and sensory approach integrated has been implanted to study the effect of the incorporation of these natural food additives in the matrix of a fermented milk type set yogurt, to study the stability of the product during the periods of fermentation and post-acidification over a period of 21 days at 4°C. Pectin was extracted in hot HCl solution. Thermo-precipitation was carried out to obtain the whey proteins while the gelatin was extracted by hydrolysis of the collagen from bovine ossein. The fermented milk was prepared by varying the concentration of the incorporated additives. The measures and controls carried performed periodically on fermented milk experimental tests were carried out: pH, acidity, viscosity, the enumeration of Streptococcus thermophilus, cohesiveness, adhesiveness, taste, aftertaste, whey exudation, and odor. It appears that the acidity, viscosity, and number of Streptococcus thermophilus increased with increasing concentration of additive added in the experimental tests. Indeed, it seems clear that the quality of fermented milk and storability is more improved than the incorporation rate is high. The products showed a better test and a firmer texture limiting the whey exudation.

Keywords: fermented milk, pectin, gelatin, whey proteins, functional properties, quality, conservation, valorization

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Authors: Salah Hassab Elnaby, Omnia Hamdy, Aziza Ahmed Hassan, Salwa Abdelkawi, Ibrahim Abdelhalim

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Laser corneal reshaping has been proposed as a successful treatment of many refraction disorders. However, some physical and chemical demonstrations of the laser effect upon interaction with the corneal tissue are still not fully explained. Therefore, different computational and mathematical models have been implemented to predict the depth of the ablated channel and calculate the ablation threshold and the local temperature rise. In the current paper, we present a modified model that aims to answer some of the open questions about the ablation threshold, the ablation rate, and the physical and chemical mechanisms of that action. The proposed model consists of three parts. The first part deals with possible photochemical reactions between the incident photons and various components of the cornea (collagen, water, etc.). Such photochemical reactions may end by photo-ablation or just the electronic excitation of molecules. Then a chemical reaction is responsible for the ablation threshold. Finally, another chemical reaction produces fragments that can be cleared out. The model takes into account all processes at the same time with different probabilities. Moreover, the effect of applying different laser wavelengths that have been studied before, namely the common excimer laser (193-nm) and the solid state lasers (213-nm & 266-nm), has been investigated. Despite the success and ubiquity of the ArF laser, the presented results reveal that a carefully designed 213-nm laser gives the same results with lower operational drawbacks. Moreover, the use of mode locked laser could also decrease the risk of heat generation and diffusion.

Keywords: UV lasers, mathematical model, corneal ablation, photochemical ablation

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Authors: Amin Jabbari

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The state of the art in major 3D printing technologies, such as powder-based and slurry based, has led researchers to investigate the ability to fabricate bone scaffolds for bone tissue engineering using biomaterials. In addition, 3D printing technology can simulate mechanical and biological surface properties and print with high precision complex internal and external structures that match their functional properties. Polymer matrix composites reinforced with particulate bioceramics, hydrogels reinforced with particulate bioceramics, polymers coated with bioceramics, and non-porous bioceramics are among the materials that can be investigated for bone scaffold printing. Furthermore, it was shown that the introduction of high-density micropores into the sparingly dissolvable CSiMg10 and dissolvable CSiMg4 shell layer inevitably leads to a nearly 30% reduction in compressive strength, but such micropores can easily influence the ion release behavior of the scaffolds. Also, biocompatibility tests such as cytotoxicity, hemocompatibility and genotoxicity were tested on printed parts. The printed part was tested in vitro, and after 24-26 h for cytotoxicity, and 4h for hemocompatibility test, the CSiMg4@CSiMg10-p scaffolds were found to have significantly higher osteogenic capability than the other scaffolds of implantation. Overall, these experimental studies demonstrate that 3D printed, additively-manufactured bioceramic calcium (Ca)-silicate scaffolds with appropriate pore dimensions are promising to guide new bone ingrowth.

Keywords: AM, 3D printed implants, bioceramic, tissue engineering

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Authors: B. Kodedova, E. Filova, M. Kralovic, E. Amler

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Vitiligo is the most common depigmentation disorder of the skin characterized by loss of melanocyte in the epidermis that leads to white lesions. One of the possible treatments is autologous transplantation of melanocytes. Biodegradable electrospun polymeric nanofibers provide good mechanical properties and could serve as suitable scaffold for epithelial cells cultivation and follow up transplantation. Moreover the microarchitecture of nanofibers mimics the structure of extracellular matrix and its porosity allows nutrients and waste exchange. The aim of this work was to develop biocompatible and biodegradable polymeric scaffolds suitable for autologous melanocytes transplantation. Electrospun polyvinyl alcohol (PVA) nanofibers were modified by cold methane plasma to lower their hydrofility and to achieve better adhesion, proliferation and viability of the murine melanocyte (Melan-a). Cells were seeded on the modified scaffolds and their adhesion, metabolic activity, proliferation and melanin synthesis was evaluated and compared to non-modified scaffolds. Results clearly indicate that cold methane plasma modified PVA nanofibers are suitable for melanocyte cultivation and may be future candidate for vitiligo treatment. Furthermore, the nanofibers can be functionalized with various bioactive substances, for enhancement of the melanocyte proliferation, melanogenesis or healing and regenerative processes. The project was supported by the Ministry of Education, Youth and Sports NPU I: LO1309 and by Grant Agency of Charles University (grant No. 1228214).

Keywords: melanocyte, nanofibers, polyvinyl alcohol, plasma modification

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Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: To describe a novel technique of trabeculectomy targeting triple modulation on wound healing to increase the overall success rate. Method: Ten eyes of 10 patients underwent trabeculectomy with subconjunctival mitomycin C (0.4mg/ml for 4 minutes) application combined with Ologen implantation subconjunctivally and subsclerally. Five of these patients underwent additional phacoemulsification with intraocular lens implantation. The Ologen implant was wet with 0.1 ml Bevacizumab. Result: All the eyes achieved target intraocular pressure (IOP), which was maintained until one year of follow-up. Two patients needed anterior chamber reformation at day two post surgery. One patient needed cataract surgery after four months of surgery and achieved target intraocular pressure on two topical antiglaucoma medicines. Conclusion: Vascular endothelial growth factor (VEGF) concentration has been seen to increase in the aqueous humor after filtration surgery. Ologen implantation helps in collagen remodelling, antifibroblastic response, and acts as a spacer. Bevacizumab augmented Ologen, in addition, targets the increased VEGF and helps in decreasing scarring. Anti-VEGF augmented Ologen in trabeculectomy with mitomycin C (MMC) hence appears to have encouraging short-term intraocular pressure control.

Keywords: ologen, anti-VEGF, trabeculectomy, scarring

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Authors: S. Bilal, S. A. Bhat, I. Hussain, J. D. Parrah, S. P. Ahmad, M. R. Mir

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Background: The wound healing involves a highly coordinated cascade of cellular and immunological response over a period including coagulation, inflammation, granulation tissue formation, epithelialization, collagen synthesis and tissue remodeling. Wounds in aged heal more slowly than those in younger, mainly because of comorbidities that occur as one age. The present study is about the influence of age on wound healing. 1x1cm^2 (100 mm) wounds were created on the back of the animal. The animals were divided into two groups; one group had animals in the age group of 3-9 months while another group had animals in the age group of 15-21 months. Materials and Methods: 24 clinically healthy rabbits in the age group of 3-21 months were used as experimental animals and divided into two groups viz A and B. All experimental parameters, i.e., Excision wound model, Measurement of wound area, Protein extraction and estimation, Protein extraction and estimation and DNA extraction and estimation were done by standard methods. Results: The parameters studied were wound contraction, hydroxyproline, glucosamine, protein, and DNA. A significant increase (p<0.005) in the hydroxyproline, glucosamine, protein and DNA and a significant decrease in wound area (p<0.005) was observed in the age group of 3-9 months when compared to animals of an age group of 15-21 months. Wound contraction together with hydroxyproline, glucosamine, protein and DNA estimations suggest that advanced age results in retarded wound healing. Conclusion: The decrease wound contraction and accumulation of hydroxyproline, glucosamine, protein and DNA in group B animals may be associated with the reduction or delay in growth factors because of the advancing age.

Keywords: age, wound healing, excision wound, hydroxyproline, glucosamine

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Authors: Haiyan Wang, Dongyun Wang, Yongyong Yan, Richard T. Jaspers, Gang Wu

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Mesenchymal stem cell and 3D printing-based bone tissue engineering present a promising technique to repair large-volume bone defects. Its success is highly dependent on cell attachment, spreading, osteogenic differentiation, and in vivo survival of stem cells on 3D-printed scaffolds. In this study, human salivary histatin-1 (Hst1) was utilized to enhance the interactions between human adipose-derived stem cells (hASCs) and 3D-printed β-tricalcium phosphate (β-TCP) bioceramic scaffolds. Fluorescent images showed that Hst1 significantly enhanced the adhesion of hASCs to both bioinert glass and 3D-printed β-TCP scaffold. In addition, Hst1 was associated with significantly higher proliferation and osteogenic differentiation of hASCs on 3D-printed β-TCP scaffolds. Moreover, coating 3D-printed β-TCP scaffolds with histatin significantly promotes the survival of hASCs in vivo. The ERK and p38 but not JNK signaling was found to be involved in the superior adhesion of hASCs to β-TCP scaffolds with the aid of Hst1. In conclusion, Hst1 could significantly promote the adhesion, spreading, osteogenic differentiation, and in vivo survival of hASCs on 3D-printed β-TCP scaffolds, bearing a promising application in stem cell/3D printing-based constructs for bone tissue engineering.

Keywords: 3d printing, adipose-derived stem cells, bone tissue engineering, histatin-1, osteogenesis

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Authors: Asif Husain, Shah Alam Khan

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Coumarins and flavones are oxygen containing heterocyclic compounds which are present in various biologically active compounds. Both the heterocyclic rings are associated with diverse biological actions, therefore considered as an important scaffold for the design of molecules of pharmaceutical interest. Aim: To synthesize and evaluate the in vivo anti-inflammatory activity of few coumrain and flavone derivatives containing 1,4 dioxane ring system. Materials and methods: Coumarin derivatives (3a-d) were synthesized by reacting 7,8 dihydroxy coumarin (2a) and its 4-methyl derivative (2b) with epichlorohydrin/ethylene dibromide. The flavone derivatives (10a-d) were prepared by using quercetin and 3,4 dihydroxy flavones. Compounds of both the series were also evaluated for their anti-inflammatory, analgesic activity and ulcerogenicity in animal models by reported methods. Results and Discussion: The structures of all newly synthesized compounds were confirmed with the help of IR, 1H NMR, 13C NMR and Mass spectral studies. Elemental analyses data for each element analyzed (C, H, N) was found to be within acceptable range of ±0.4 %. Flavone derivatives, but in particular quercetin containing 1,4 dioxane ring system (10d) showed better anti-inflammatory and analgesic activity along with reduced gastrointestinal toxicity as compared to other synthesized compounds. The results of anti-inflammatory and analgesic activities of both the series are comparable with the positive control, diclofenac. Conclusion: Compound 10d, a quercetin derivative, emerged as a lead molecule which exhibited potent anti-inflammatory and analgesic activity with significant reduced gastric toxicity.

Keywords: analgesic, anti-inflammatory, 1, 4 dioxane, coumarin, flavone

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Authors: Fernando G. Torres, Donna M. Ebenstein, Monica Merino

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Most fish are covered by a protective external armour. The characteristics of these armours depend on the individual elements that form them, such as scales, scutes or dermal plates. In this work, we assess the properties of two different types of protective elements: scales from A. gigas and dermal plates from P. pardalis. A. Gigas and P. Pardalis are two Amazonian fish with a rather prehistoric aspect. They have large scales and dermal plates that form two different types of protective body armours. Although both scales and dermal plates are formed by collagen and hydroxyapatite, their structures display remarkable differences. The structure and composition of the samples were assessed by means of X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). Morphology studies were carried out using a Scanning Electron Microscopy (SEM). Nanoindentation tests were performed to measure the reduced moduli in A. gigas scales and P. pardalis plates. The similarities and differences between scales and dermal plates are discussed based on the experimental results. Both protective armours are designed to be lightweight, flexible and tough. A. Gigas scales are are light laminated composites, while P. pardalis dermal plates show a sandwich like structure with dense outer layers and a porous inner matrix. It seems that the armour of P. pardalis is more suited for a bottom-dwelling fish and allows for protection against predators. The scales from A. Gigas are more adapted to give protection to a swimming fish. The information obtained from these studies is also important for the development of bioinspired nanocomposites, with potential applications in the biomedical field.

Keywords: pterygoplichthys pardalis, dermal plates arapaima gigas, fish scales

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Authors: Jelena S. Kiurski, Vesna S. Kecić, Snežana M. Aksentijević

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The identification and evaluation of organic and inorganic pollutants were performed in a flexographic facility in Novi Sad, Serbia. Air samples were collected and analyzed in situ, during 4-hours working time at five sampling points by the mobile gas chromatograph and ozonometer at the printing of collagen casing. Experimental results showed that the concentrations of isopropyl alcohol, acetone, total volatile organic compounds and ozone varied during the sampling times. The highest average concentrations of 94.80 ppm and 102.57 ppm were achieved at 200 minutes from starting the production for isopropyl alcohol and total volatile organic compounds, respectively. The mutual dependences between target hazardous and microclimate parameters were confirmed using a multiple linear regression model with software package STATISTICA 10. Obtained multiple coefficients of determination in the case of ozone and acetone (0.507 and 0.589) with microclimate parameters indicated a moderate correlation between the observed variables. However, a strong positive correlation was obtained for isopropyl alcohol and total volatile organic compounds (0.760 and 0.852) with microclimate parameters. Higher values of parameter F than F_critical for all examined dependences indicated the existence of statistically significant difference between the concentration levels of target pollutants and microclimates parameters. Given that, the microclimate parameters significantly affect the emission of investigated gases and the application of eco-friendly materials in production process present a necessity.

Keywords: flexographic printing, indoor air, multiple regression analysis, pollution emission

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: A few lines of evidence show that Sulforaphane (SFN) has anti-fibrosis effect in liver tissue via Nrf2-mediated inhibition of TGF-β/Smad signaling. However, its effects on muscular dystrophic fibrosis remain unknown. This work was undertaken to evaluate the effects of SFN on fibrosis in dystrophic muscle. Methods: 3-month-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 3 months. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Fibrosis in skeletal muscles was analyzed by Sirius red staining. Histology and morphology of skeletal muscles were investigated by H&E staining. Moreover, the expressions of Nrf2, NQO1, HO-1, and TGF-β/Smad signaling pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment significantly decreased and improved morphological features in mdx muscles. Moreover, SFN increased the expression of muscle phase II enzymes NQO1 and HO-1 and significantly decreased the expression of TGF-β1，p-smad2, p-smad3, α-SMA, fibronectin, collagen I, PAI-1, and TIMP-1 in Nrf2 dependent manner. Additionally, SFN significantly decreased the expression of CD45 and TNF-α. Conclusions: Collectively, these results show that SFN can ameliorate muscle fibrosis in mdx mice by Nrf2-induced inhibition of TGF-β/Smad signaling pathway, which indicate Nrf2 may be useful for the treatment of muscular dystrophy.

Keywords: sulforaphane, Nrf2, TGF-β/smad signaling, duchenne muscular dystrophy, fibrosis

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Authors: Sachin Latiyan, T. S. Sampath Kumar, Mukesh Doble

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Natural polymer based nanofibrous wound dressings have gained increased attention because of their high surface area, bioactivity, biodegradability and resemblance to extracellular matrix. Agarose (a natural polymer) have been used largely for angiogenesis, cartilage formation and wound healing applications. However, electrospinning of agarose is tedious thereby rendering limited studies on fabrication and evaluation of agarose based nanofibrous wound dressings. Thus, present study focuses on the fabrication of agarose (10% w/v)/ polyvinyl alcohol (12% w/v) based multifunctional nanofibrous scaffolds. Zinc citrate (1, 3 and 5% w/w of the polymer) was added as a potential antibacterial agent to combat wound infections. The fabricated scaffolds exhibit ~500% swelling (in phosphate buffer saline) with enhanced mechanical strength which is suitable for most of the wound healing applications. In vitro studies were found to reveal an increased migration and proliferation of L929 mouse fibroblasts with agarose blends w.r.t to the control. The fabricated dressings were found to be effective against both Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacterial strains. Hence, a multifunctional (as provides effective swelling and mechanical support along with antibacterial property), natural product based, eco-friendly scaffold was successfully fabricated to serve as a potential wound dressing material.

Keywords: antibacterial dressings, benign solvent, nanofibrous agarose, biocompatibility, enhanced swelling and mechanical strength, biopolymeric dressings

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Authors: Deepika Saini, Sandeep Jain, Ajay Kumar

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The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.

Keywords: antimalarial activity, chalcone, docking, quinoline

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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Authors: Alisan Kayabolen, Dilek Keskin, Ferit Avcu, Andac Aykan, Fatih Zor, Aysen Tezcaner

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Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, only very thin implants can be used in vivo since vascularization is still a problem for thick implants. Another problem is finding a biocompatible scaffold with good mechanical properties. In this study, the aim is to develop a thick vascularized adipose tissue that will integrate with the host, and perform its in vitro and in vivo characterizations. For this purpose, a hydrogel of decellularized adipose tissue (DAT) and fibroin was produced, and both endothelial cells and adipocytes that were differentiated from adipose derived stem cells were encapsulated in this hydrogel. Mixing DAT with fibroin allowed rapid gel formation by vortexing. It also provided to adjust mechanical strength by changing fibroin to DAT ratio. Based on compression tests, gels of DAT/fibroin ratio with similar mechanical properties to adipose tissue was selected for cell culture experiments. In vitro characterizations showed that DAT is not cytotoxic; on the contrary, it has many natural ECM components which provide biocompatibility and bioactivity. Subcutaneous implantation of hydrogels resulted with no immunogenic reaction or infection. Moreover, localized empty hydrogels gelled successfully around host vessel with required shape. Implantations of cell encapsulated hydrogels and histological analyses are under study. It is expected that endothelial cells inside the hydrogel will form a capillary network and they will bind to the host vessel passing through hydrogel.

Keywords: adipose tissue engineering, decellularization, encapsulation, hydrogel, vascularization

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Authors: Kusum Kumari, Ramesh Banoth, V. S. Reddy Channu

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Organic-inorganic perovskite solar cells (PrSCs) have emerged as a promising solar photovoltaic technology in terms of realizing high power conversion efficiency (PCE). However, their limited lifetime and poor device stability limits their commercialization in future. In this regard, interface engineering of the electron transport layer (ETL) using 2D materials have been currently used owing to their high carrier mobility, high thermal stability and tunable work function, which in turn enormously impact the charge carrier dynamics. In this work, we report an easy and effective way of simultaneously enhancing the efficiency of PrSCs along with the long-term stability through interface engineering via the incorporation of 2D-Molybdenum disulfide (2D-MoS₂, few layered nanoflakes) in mesoporous-Titanium dioxide (mp-TiO₂)scaffold electron transport buffer layer, and using poly 3-hexytheophene (P3HT) as hole transport layers. The PSCs were fabricated in ambient air conditions in device configuration, FTO/c-TiO₂/mp-TiO₂:2D-MoS₂/CH3NH3PbI3/P3HT/Au, with an active area of 0.16 cm². The best device using c-TiO₂/mp-TiO₂:2D-MoS₂ (0.5wt.%) ETL exhibited a substantial increase in PCE ~13.04% as compared to PCE ~8.75% realized in reference device fabricated without incorporating MoS₂ in mp-TiO₂ buffer layer. The incorporation of MoS₂ nanoflakes in mp-TiO₂ ETL not only enhances the PCE to ~49% but also leads to better device stability in ambient air conditions without encapsulation (retaining PCE ~86% of its initial value up to 500 hrs), as compared to ETLs without MoS₂.

Keywords: perovskite solar cells, MoS₂, nanoflakes, electron transport layer

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Authors: R. Tajau, R. Rohani, M. S. Alias, N. H. Mudri, K. A. Abdul Halim, M. H. Harun, N. Mat Isa, R. Che Ismail, S. Muhammad Faisal, M. Talib, M. R. Mohamed Zin

Abstract:

Bio-based polymeric materials are increasingly used for a variety of applications, including surface coating, drug delivery systems, and tissue engineering. These polymeric materials are ideal for the aforementioned applications because they are derived from natural resources, non-toxic, low-cost, biocompatible, and biodegradable, and have promising thermal and mechanical properties. The nature of hydrocarbon chains, carbon double bonds, and ester bonds allows various sources of oil (edible), such as soy, sunflower, olive, and oil palm, to fine-tune their particular structures in the development of innovative materials. Palm oil can be the most eminent raw material used for manufacturing new and advanced natural polymeric materials involving radiation techniques, such as coating resins, nanoparticles, scaffold, nanotubes, nanocomposites, and lithography for different branches of the industry in countries where oil palm is abundant. The radiation technique is among the most versatile, cost-effective, simple, and effective methods. Crosslinking, reversible addition-fragmentation chain transfer (RAFT), polymerisation, grafting, and degradation are among the radiation mechanisms. Exposure to gamma, EB, UV, or laser irradiation, which are commonly used in the development of polymeric materials, is used in these mechanisms. Therefore, this review focuses on current radiation processing technologies for the development of various radiation-curable bio-based polymeric materials with a promising future in biomedical and industrial applications. The key focus of this review is on radiation curable palm oil-based products, which have been published frequently in recent studies.

Keywords: palm oil, radiation processing, surface coatings, VOC

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Authors: Romeo A. Botes, Imelda Smit

Abstract:

The demands of an ever changing and complex higher education environment, along with the profile of modern learners challenge current approaches to assessment and feedback. More learners enter the education system every year. The younger generation expects immediate feedback. At the same time, feedback should be meaningful. The assessment of practical activities in programming poses a particular problem, since both lecturers and learners in the information and computer science discipline acknowledge that paper-based assessment for programming subjects lacks meaningful real-life testing. At the same time, feedback lacks promptness, consistency, comprehensiveness and individualisation. Most of these aspects may be addressed by modern, technology-assisted assessment. The focus of this paper is the continuous development of an artefact that is used to assist the lecturer in the assessment and feedback of practical programming activities in a senior database programming class. The artefact was developed using three Design Science Research cycles. The first implementation allowed one programming activity submission per assessment intervention. This pilot provided valuable insight into the obstacles regarding the implementation of this type of assessment tool. A second implementation improved the initial version to allow multiple programming activity submissions per assessment. The focus of this version is on providing scaffold feedback to the learner – allowing improvement with each subsequent submission. It also has a built-in capability to provide the lecturer with information regarding the key problem areas of each assessment intervention.

Keywords: programming, computer-aided assessment, technology-assisted assessment, programming assessment software, design science research, mixed-method

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Authors: Sharda Nara, Bansi Dhar Malhotra

Abstract:

Investigation of the vitamins as an electron transfer mediator could significantly assist in merging the area of tissue engineering and electronics required for the implantable therapeutic devices. The present study report that the molecules of folic acid released by Providencia rettgeri via fermentation route under the anoxic condition of the microbial fuel cell (MFC) exhibit characteristic electrochemical and optical properties, as indicated by absorption spectroscopy, photoluminescence (PL), and cyclic voltammetry studies. The absorption spectroscopy has depicted an absorption peak at 263 nm with a small bulge around 293 nm on day two of bacterial culture, whereas an additional peak was observed at 365 nm on the twentieth day. Furthermore, the PL spectra has indicated that the maximum emission occurred at various wavelengths 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm. The change of emission spectra with varying excitation wavelength might be indicating the presence of tunable optical bands in the folic acid molecules co-related with the redox activity of the molecules. The results of cyclic voltammetry studies revealed that the oxidation and reduction occurred at 0.25V and 0.12V, respectively, indicating the electrochemical behavior of the folic acid. This could be inferred that the released folic acid molecules in a MFC might undergo inter as well as intra molecular electron transfer forming different intermediate states while transferring electrons to the electrode surface. Synchronization of electrochemical and optical properties of folic acid molecules could be potentially promising for the designing of electroactive scaffold and biocompatible conductive surface for the applications of tissue engineering and biofuel cells, respectively.

Keywords: biofuel cell, electroactivity, folic acid, tissue engineering

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Authors: Mandy W. M. Chan, Samantha Y. N. Shek, Chi K. Yeung, Taro Kono, Henry H. L. Chan

Abstract:

Fractional radiofrequency devices have shown to improve skin texture such as smoothness, rhytides, brightness as well as atrophic acne scars by increasing dermal thickness, dermal collagen content and dermal fibrillin content. The objective of the study is to assess the efficacy and adverse effects of this device on Asian patients with skin textural changes. In this study, 20 Chinese patients (ranging from 21-60 years old) with irregularities of skin texture, rhytides and acne scars were recruited. Patients received six treatments at 2-4 week intervals. Treatment was initiated with maximum energy tolerated and was adjustable during treatment if patients felt excessive discomfort. A total of two passes were delivered at each session. Physician assessment and standardized photographs were taken at baseline, all treatment visits and at one, two, and six month after final treatment. As a result, 17 patients were recruited and completed the study according to the study protocol. One patient withdrew after the first treatment due to reaction to local anesthesia and two patients were lost to follow-up. At six months follow-up, 71% of the patients were satisfied and 24% were very satisfied, while treatment physician reported various degrees of improvement based on the global assessment scale in 60% of the subjects. Anticipated side effects including erythema, edema, pinpoint bleeding, scabs formation and flare of acne were recorded, but there were no serious adverse effects noted. Conclude up, the use of fractional radiofrequency improves skin texture and appears to be safe in Asian patients. No long-term serious adverse effect was noted.

Keywords: Asian, fractional radiogrequency, skin, texture

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Authors: Yang Zhao, Feng Zhang, Xuanchu Duan

Abstract:

Trans-differentiation of human Tenon fibroblasts (HTFs) to myo-fibroblasts and fibrosis of episcleral tissue are the most common reasons for the failure of glaucoma filtration surgery, with limited treatment options like antimetabolites which always have side-effects such as leakage of filter bulb, infection, hypotony, and endophthalmitis. Rosiglitazone, a specific thiazolidinedione is a synthetic high-affinity ligand for PPAR-r, which has been used in the treatment of type2 diabetes, and found to have pleiotropic functions against inflammatory response, cell proliferation and tissue fibrosis and to benefit to a variety of diseases in animal myocardium models, steatohepatitis models, etc. Here, in vitro we cultured primary HTFs and stimulated with TGF- β to induced myofibrogenic, then treated cells with Rosiglitazone to assess for fibrogenic response. In vivo, we used rabbit glaucoma model to establish the formation of post- trabeculectomy scarring. Then we administered subconjunctival injection with Rosiglitazone beside the filtering bleb, later protein, mRNA and immunofluorescence of fibrogenic markers are checked, and filtering bleb condition was measured. In vitro, we found Rosiglitazone could suppressed proliferation and migration of fibroblasts through macroautophagy via TGF- β /Smad signaling pathway. In vivo, on postoperative day 28, the mean number of fibroblasts in Rosiglitazone injection group was significantly the lowest and had the least collagen content and connective tissue growth factor. Rosiglitazone effectively controlled human and rabbit fibroblasts in vivo and in vitro. Its subconjunctiiva application may represent an effective, new avenue for the prevention of scarring after glaucoma surgery.

Keywords: fibrosis, glaucoma, macroautophagy, rosiglitazone

Procedia PDF Downloads 246

Authors: I. Szer, J. Szer, K. Czarnocki, E. Błazik-Borowa

Abstract:

People on construction scaffoldings work in dynamically changing, often unfavourable climate. Additionally, this kind of work is performed on low stiffness structures at high altitude, which increases the risk of accidents. It is therefore desirable to define the parameters of the work environment that contribute to increasing the construction worker occupational safety level. The aim of this article is to present how changes in microclimate parameters on scaffolding can impact the development of dangerous situations and accidents. For this purpose, indicators based on the human thermal balance were used. However, use of this model under construction conditions is often burdened by significant errors or even impossible to implement due to the lack of precise data. Thus, in the target model, the modified parameter was used – apparent environmental temperature. Apparent temperature in the proposed Scaffold Use Risk Assessment Model has been a perceived outdoor temperature, caused by the combined effects of air temperature, radiative temperature, relative humidity and wind speed (wind chill index, heat index). In the paper, correlations between component factors and apparent temperature for facade scaffolding with a width of 24.5 m and a height of 42.3 m, located at south-west side of building are presented. The distribution of factors on the scaffolding has been used to evaluate fitting of the microclimate model. The results of the studies indicate that observed ranges of apparent temperature on the scaffolds frequently results in a worker’s inability to adapt. This leads to reduced concentration and increased fatigue, adversely affects health, and consequently increases the risk of dangerous situations and accidental injuries

Keywords: apparent temperature, health, safety work, scaffoldings

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Authors: Anjelika Kremer, Irina Nachimov, Dan Justo

Abstract:

Background: C-reactive protein (CRP) serum levels are commonly measured in hospitalized patients. Elevated admission CRP serum levels and in-hospital mortality has been seldom studied in the general population of elderly patients admitted to the acute Geriatrics department. Methods: A retrospective cross-sectional study was conducted at a tertiary medical center. Included were all elderly patients (age 65 years or more) admitted to a single acute Geriatrics department from the emergency room between April 2014 and January 2015. CRP serum levels were measured routinely in all patients upon the first 24 hours of admission. A logistic regression analysis was used to study if admission CRP serum levels were associated with in-hospital mortality independent of age, gender, functional status, and co-morbidities. Results: Overall, 498 elderly patients were included in the analysis: 306 (61.4%) female patients and 192 (38.6%) male patients. The mean age was 84.8±7.0 years (median: 85 years; IQR: 80-90 years). The mean admission CRP serum levels was 43.2±67.1 mg/l (median: 13.1 mg/l; IQR: 2.8-51.7 mg/l). Overall, 33 (6.6%) elderly patients died during the hospitalization. A logistic regression analysis showed that in-hospital mortality was independently associated with history of stroke (p < 0.0001), heart failure (p < 0.0001), and admission CRP serum levels (p < 0.0001) – and to a lesser extent with age (p = 0.042), collagen vascular disease (p=0.011), and recent venous thromboembolism (p=0.037). Receiver operating characteristic (ROC) curve showed that admission CRP serum levels predict in-hospital mortality fairly with an area under the curve (AUC) of 0.694 (p < 0.0001). Cut-off value with maximal sensitivity and specificity was 19.7 mg/L. Conclusions: Admission CRP serum levels may be used to predict in-hospital mortality in the general population of elderly patients admitted to the acute Geriatrics department.

Keywords: c-reactive protein, elderly, mortality, prediction

Procedia PDF Downloads 218

Authors: MyungGu Yeo, JongHan Ha, Gi-Hoon Yang, JaeYoon Lee, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

Abstract:

Tissue engineering is a rapidly growing interdisciplinary research area that may provide options for treating damaged tissues and organs. As a promising technique for regenerating various tissues, this technology requires biomedical scaffolds, which serve as an artificial extracellular matrix (ECM) to support neotissue growth. Electrospun micro/nanofibers have been used widely in tissue engineering because of their high surface-area-to-volume ratio and structural similarity to extracellular matrix. However, low mechanical sustainability, low 3D shape-ability, and low cell infiltration have been major limitations to their use. In this work, we propose new hybrid scaffolds interlayered with cell-laden electrospun micro/nano fibers and poly(caprolactone) microstructures. Also, we applied various concentrations of alginate and electric field strengths to determine optimal conditions for the cell-electrospinning process. The combination of cell-laden bioink (2 ⅹ 10^5 osteoblast-like MG63 cells/mL, 2 wt% alginate, 2 wt% poly(ethylene oxide), and 0.7 wt% lecithin) and a 0.16 kV/mm electric field showed the highest cell viability and fiber formation in this process. Using these conditions and PCL microstructures, we achieved mechanically stable hybrid scaffolds. In addition, the cells embedded in the fibrous structure were viable and proliferated. We suggest that the cell-embedded hybrid scaffolds fabricated using the cell-electrospinning process may be useful for various soft- and hard-tissue regeneration applications.

Keywords: bioink, cell-laden scaffold, micro/nanofibers, poly(caprolactone)

Procedia PDF Downloads 352

Authors: Mohammed Flaih Alotaibi, Rasheed Ahemad Shaik, Mohammed Z. Nasrullah

Abstract:

Diabetic foot ulcers are the foremost global healthcare burden. Hyperglycemia in diabetics is incriminating in impeding wound healing and it can allow for more severe medical issues. The study was intended to establish a nanoconjugate of cordycepin-melittin (COR-MEL) and evaluate its healing effects in wounded diabetic rats. Diabetes induced by injecting streptozotocin intraperitoneally (50 mg/kg, body weight). Therefore, animals were classified into various groups; diabetic untreated, vehicle-treated, COR alone, MEL alone, and COR-MEL nanoconjugate treated, respectively. Animals with diabetes were exposed to excision and treated with Vehicle, COR, MEL, or COR-MEL nanoconjugate topically. After 14 days, the wounded skin was sliced and subjected to histological and biochemical assessments. The formulated nanoconjugate has a particle size of 253.5± 17.4 nm by a polydispersity index of 0.36 ± 0.05, and a zeta potential of 1.72 ± 0.3 mV. The study demonstrated an accelerated wound contraction in COR-MEL-treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde and exhaustion of superoxide dismutase and glutathione peroxidase enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of proinflammatory cytokines (IL-6 and TNF-α). Additionally, the nanoconjugate exhibits a strong expression of growth factors (TGF-β1, VEGF-A, and PDGFR-β), indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1. Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Keywords: diabetic wounds, cordycepin, melittin, nanoconjugate, wound healing

Procedia PDF Downloads 54

Authors: Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Bath, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas A. White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss

Abstract:

Ultrafast isomerization of retinal is the primary step in a range of photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an X-ray laser. Twenty snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a highly-twisted geometry and emerging in the 13-cis conformation. The aspartic acid residues and functional water molecules in proximity of the retinal Schiff base respond collectively to formation and decay of the initial excited state and retinal isomerization. These observations reveal how the protein scaffold guides this remarkably efficient photochemical reaction.

Keywords: bacteriorhodopsin, free-electron laser, retinal isomerization mechanism, time-resolved crystallography

Procedia PDF Downloads 216