Search results for: retinal Müller cell
598 Biosurfactants Production by Bacillus Strain from an Environmental Sample in Egypt
Authors: Mervat Kassem, Nourhan Fanaki, F. Dabbous, Hamida Abou-Shleib, Y. R. Abdel-Fattah
Abstract:
With increasing environmental awareness and emphasis on a sustainable society in harmony with the global environment, biosurfactants are gaining prominence and have already taken over for a number of important industrial uses. They are produced by living organisms, for examples Pseudomonas aeruginosa which produces rhamnolipids, Candida (formerly Torulopsis) bombicola, which produces high yields of sophorolipids from vegetable oils and sugars and Bacillus subtilis which produces a lipopeptide called surfactin. The main goal of this work was to optimize biosurfactants production by an environmental Gram positive isolate for large scale production with maximum yield and low cost. After molecular characterization, phylogenetic tree was constructed where it was found to be B. subtilis, which close matches to B. subtilis subsp. subtilis strain CICC 10260. For optimizing its biosurfactants production, sequential statistical design using Plackett-Burman and response surface methodology, was applied where 11 variables were screened. When analyzing the regression coefficients for the 11 variables, pH, glucose, glycerol, yeast extract, ammonium chloride and ammonium nitrate were found to have a positive effect on the biosurfactants production. Ammonium nitrate, pH and glucose were further studied as significant independent variables for Box-Behnken design and their optimal levels were estimated and were found to be 7.328 pH value, 3 g% glucose and 0.21g % ammonium nitrate yielding high biosurfactants concentration that reduced the surface tension of the culture medium from 72 to 18.16 mN/m. Next, kinetics of cell growth and biosurfactants production by the tested B. subtilis isolate, in bioreactor was compared with that of shake flask where the maximum growth and specific growth (µ) in the bioreactor was higher by about 25 and 53%, respectively, than in shake flask experiment, while the biosurfactants production kinetics was almost the same in both shake flask and bioreactor experiments.Keywords: biosurfactants, B. subtilis, molecular identification, phylogenetic trees, Plackett-Burman design, Box-Behnken design, 16S rRNA
Procedia PDF Downloads 410597 Self-Healing Hydrogel Triggered by Magnetic Microspheres to Control Glutathione Release for Cartilage Repair
Authors: I-Yun Cheng, Min-Yu Chiang, Shwu-Jen Chang, San-Yuan Chen
Abstract:
Osteoarthritis (OA) is among the most challenging joint diseases, and as far as we know, there is currently no exact and effective cure for it because it has low self-repair ability due to lack of blood vessels and low cell density in articular cartilage. So far, there have been several methods developed to treat cartilage disorder. The most common method is to treat the high molecular weight of hyaluronic acid (HA) injection, but it will degrade after a period of time, so the patients need to inject HA repeatedly. In recent years, self-healing hydrogel has drawn considerable attention because it can recover its initial mechanical properties after damaged and further increase the lifetime of the hydrogel. Here, we aim to develop a self-healable composite hydrogel combined with magnetic microspheres to trigger glutathione(GSH) release for promoting cartilage repair. We use HA-cyclodextrin (CD) as host polymer and poly(acrylic acid)-ferrocene (pAA-Fc) as guest polymer to form the self-healable HA-pAA hydrogel by host and guest interaction where various graft amount of pAA-Fc (pAA:Fc= 1:2, 1:1.5, 1:1, 2:1, 4:1) was conducted to develop different mechanical strength hydrogel. The rheology analysis showed that the 4:1 of pAA-Fc has higher mechanical strength than other formulations. On the other hand, iron oxide nanoparticle, poly(lactic-co-glycolic acid) (PLGA) and polyethyleneimine (PEI) were used to synthesize porous magnetic microspheres via double emulsification water-in-oil-in-water (W/O/W) to increase GSH loading which acted as a reductant to control the hydrogel crosslink density and promote hydrogel self-healing. The results show that the porous magnetic microspheres can be loaded with 70% of GSH and sustained release about 50% of GSH after 24 hours. More importantly, the HA-pAA composite hydrogel can self-heal rapidly within 24 hours when suffering external force destruction by releasing GSH from the magnetic microspheres. Therefore, the developed the HA-pAA composite hydrogel combined with GSH-loaded magnetic microspheres can be in-vivo guided to damaged OA surface for inducing the cartilage repair by controlling the crosslinking of self-healing hydrogel via GSH release.Keywords: articular cartilage, magnetic microsphere, osteoarthritis, self-healing hydrogel
Procedia PDF Downloads 132596 Transcriptome Analysis for Insights into Disease Progression in Dengue Patients
Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee
Abstract:
Dengue virus infection is now considered as one of the most important mosquito-borne infection in human. The virus is known to promote vascular permeability, cerebral edema leading to Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Dengue infection has known to be endemic in India for over two centuries as a benign and self-limited disease. In the last couple of years, the disease symptoms have changed, manifesting severe secondary complication. So far, Delhi has experienced 12 outbreaks of dengue virus infection since 1997 with the last reported in 2014-15. Without specific antivirals, the case management of high-risk dengue patients entirely relies on supportive care, involving constant monitoring and timely fluid support to prevent hypovolemic shock. Nonetheless, the diverse clinical spectrum of dengue disease, as well as its initial similarity to other viral febrile illnesses, presents a challenge in the early identification of this high-risk group. WHO recommends the use of warning signs to identify high-risk patients, but warning signs generally appear during, or just one day before the development of severe illness, thus, providing only a narrow window for clinical intervention. The ability to predict which patient may develop DHF and DSS may improve the triage and treatment. With the recent discovery of high throughput RNA sequencing allows us to understand the disease progression at the genomic level. Here, we will collate the results of RNA-Sequencing data obtained recently from PBMC of different categories of dengue patients from India and will discuss the possible role of deregulated genes and long non-coding RNAs NEAT1 for development of disease progression.Keywords: long non-coding RNA (lncRNA), dengue, peripheral blood mononuclear cell (PBMC), nuclear enriched abundant transcript 1 (NEAT1), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS)
Procedia PDF Downloads 308595 Stereological Evaluation of Liver of Rabbit Fetuses After Transplantation of Human Wharton’s Jelly-Derived Mesenchymal Stromal/Stem Cells
Authors: Zahra Khodabandeh, Leila Rezaeian, Mohammad Amin Edalatmanesh, Asghar Mogheiseh, Nader Tanideh, Mehdi Dianatpour, Shahrokh Zare, Hossein Bordbar, Neda Baghban, Amin Tamadon
Abstract:
Background: In-utero xenotransplantation of stem cells in abnormal fetuses effectively treats several genetic illnesses. Objective: The current research aimed to evaluate structural and morphological alterations in the liver of rabbit fetuses following xenotransplantation of human Wharton’s jelly-derived mesenchymal stromal cells (hWJ-MSCs) using a stereological technique. Methods: hWJ-MSCs were isolated from the human umbilical cord, and their authenticity was established by flow cytometry and differentiation. At gestational day 14, the rabbits were anesthetized, and hWJ-MSCs were injected into the uteri of 24 fetuses. Twenty-two fetuses were born successfully. Ten rabbit liver specimens were prepared from injected fetuses, including eight rabbits on day three following birth and two rabbits on the 21st post-natal day. The non-injected fetuses were considered positive controls. The livers of the control and hWJ-MSCs-treated rabbits were fixed, processed, stained, and examined through stereological approaches. Results: In the hWJ-MSCs-treated group, the mean liver weight and volume increased by 42% and 78% compared to the control group. The total volume of the hepatocytes increased by 63% and that of sinusoids by threefold in the treated rabbits. The total volume of the central veins increased by 70%. The total number corresponding to hepatocytes in the experimental group increased by 112% compared to the rabbits in the control. The total volume of the hepatocyte nuclei in the experimental group increased by 117% compared to the rabbits in the control. Conclusion: After xenotransplantation of human MSCs, host tissue microenvironments (here, the rabbit liver) were altered, and these included quantitative factors corresponding to the liver tissue and hepatocyte morphometric indices.Keywords: xenotransplantation, mesenchymal stromal, stem cell, Wharton ‘s jelly, liver
Procedia PDF Downloads 101594 Motion Planning and Simulation Design of a Redundant Robot for Sheet Metal Bending Processes
Authors: Chih-Jer Lin, Jian-Hong Hou
Abstract:
Industry 4.0 is a vision of integrated industry implemented by artificial intelligent computing, software, and Internet technologies. The main goal of industry 4.0 is to deal with the difficulty owing to competitive pressures in the marketplace. For today’s manufacturing factories, the type of production is changed from mass production (high quantity production with low product variety) to medium quantity-high variety production. To offer flexibility, better quality control, and improved productivity, robot manipulators are used to combine material processing, material handling, and part positioning systems into an integrated manufacturing system. To implement the automated system for sheet metal bending operations, motion planning of a 7-degrees of freedom (DOF) robot is studied in this paper. A virtual reality (VR) environment of a bending cell, which consists of the robot and a bending machine, is established using the virtual robot experimentation platform (V-REP) simulator. For sheet metal bending operations, the robot only needs six DOFs for the pick-and-place or tracking tasks. Therefore, this 7 DOF robot has more DOFs than the required to execute a specified task; it can be called a redundant robot. Therefore, this robot has kinematic redundancies to deal with the task-priority problems. For redundant robots, Pseudo-inverse of the Jacobian is the most popular motion planning method, but the pseudo-inverse methods usually lead to a kind of chaotic motion with unpredictable arm configurations as the Jacobian matrix lose ranks. To overcome the above problem, we proposed a method to formulate the motion planning problems as optimization problem. Moreover, a genetic algorithm (GA) based method is proposed to deal with motion planning of the redundant robot. Simulation results validate the proposed method feasible for motion planning of the redundant robot in an automated sheet-metal bending operations.Keywords: redundant robot, motion planning, genetic algorithm, obstacle avoidance
Procedia PDF Downloads 146593 Influence of IL-1β on Hamster Blastocyst Hatching via Regulation of Hatching Associated Proteases
Authors: Madhulika Pathak, Polani Seshagiri, Vani Venkatappa
Abstract:
Blastocyst hatching is an indispensable process for successful implantation. One of the major reasons for implantation failure in IVF clinic is poor quality of embryo, which are not development/hatching-competent. Therefore, attempts are required to develop or enhance the culture system with a molecule recapitulating the autocrine/paracrine factors containing the environment of in-vivo endometrial milieu. We have tried to explore the functional molecules involved in the hamster hatching phenomenon. Blastocyst hatching is governed by several molecules that are entwined and regulate this process, among which cytokines are known to be expressed and are still least explored. Two of such cytokines we have used for our study are IL-1β and its natural antagonist IL-1ra to understand the functional dynamics of cytokines involved in the hatching process. Using hamster, an intriguing experimental model for hatching behavior, we have shown the mRNA (qPCR) and protein (ICC) expression of IL-1β, IL-1ra and IL-1 receptor type 1 throughout all the stages of morula, blastocyst and hatched blastocyst. Post-asserting the expression, the functional role is shown by supplementation studies, where IL-1β supplementation showed enhancement in hatching level (IL-1β treated: 84.1 ± 4.2% vs control: 63.7 ± 3.1 %, N=11), further confirmed by the diminishing effect of IL-1ra on hatching rate (IL-1ra treated: 27.5 ± 11.1% vs control: 67.9 ± 3.1%). The exogenous supplementation of IL-1ra decreased the survival rate of embryos and affected the viability in dose-dependent manner, establishing the importance of IL-1β in blastocyst cell survival. Previously, the cathepsin L and B were established as the proteases that were involved in the hamster hatching process. The inducing effect of IL-1β was correlated with enhanced mRNA level, as analyzed by qPCR, for both CAT L (by 1.9 ± 0.5 fold) and CAT B (by 3.5 ± 0.1) fold which was diminished in presence of IL-1ra (Cat L by 88 percent and Cat B by 94 percent. Moreover, using a specific fluorescent substrate-based assay kit, the enzymatic activity of these proteases was found to be increased in presence of IL-1β (Cat L by 2.1 ± 0.1 fold and CAT B by 2.3 ± 0.7 fold) and was curtailed in presence of IL-1ra. These observations provide functional insights with respect to the involvement of cytokines in the hatching process. This has implications in understanding the hatching biology and improving the embryo development quality in IVF clinics.Keywords: Blastocyst, Cytokines, Hatching, Interleukin
Procedia PDF Downloads 144592 Preparation Nanocapsules of Chitosan Modified With Selenium Extracted From the Lactobacillus Acidophilus and Their Anticancer Properties
Authors: Akbar Esmaeili, Mahnoosh Aliahmadi
Abstract:
This study synthesized a modified imaging of gallium@deferoxamine/folic acid/chitosan/polyaniline/polyvinyl alcohol (Ga@DFA/FA/CS/PANI/PVA). It contains Morus nigra extract by selenium nanoparticles prepared from Lactobacillus acidophilus. Using the impregnation method, Se nanoparticles were then deposited on (Ga@DFA/FA/ CS/PANI/PVA). The modified contrast agents were mixed with M. nigra extract, and investigated their antibacterial activities by applying to L929 cell lines. The influence of variable factors, including 1. surfactant, 2. solvent, 3. aqueous phase, 4. pH, 5. buffer, 6. minimum Inhibitory concentration (MIC), 7. minimum bactericidal concentration (MBC), 8. cytotoxicity on cancer cells., 9. antibiotic, 10. antibiogram, 11. release and loading, 12. the emotional effect, 13. the concentration of nanoparticles, 14. olive oil, and 15. they have investigated thermotical methods. The structure and morphology of the synthesized contrast agents were characterized by zeta potential sizer analysis (ZPS), X-Ray diffraction (XRD), Fourier-transform infrared (FT-IR), energy dispersive X-ray (EDX), ultraviolet–visible (UV–Vis) spectra, and scanning electron microscope (SEM). The experimental section was conducted and monitored by response surface methods (RSM), MTT, MIC, MBC, and cancer cytotoxic conversion assay. Antibiogram testing of NCs on Pseudomonas aeruginosa bacteria was successful and obtained MIC = 2 factors with less harmful effect. All experimental sections confirmed that our synthesized particles have potent antioxidant properties. Antibiogram testing revealed that NPS could kill P. aeruginosa and P. aeruginosa. A variety of synthetic conditions were done by diffusion emulsion method by varying parameters, the optimum state of DFA release Ga@DFA/FA/CS/PANI/PVA NPs (6 ml) with pH = 5.5, time = 3 h, NCs and DFA (3 mg), and achieved buffer (20 ml). DFA in Ga@DFA/FA/ CS/PANI/PVA was released and showed an absorption peak at 378 nm by applying a 300-rpm magnetic rate. In this report, Ga decreased the harmful effect on the human body.Keywords: nanocapsules, technolgy, biology, nano
Procedia PDF Downloads 40591 Shared Decision Making in Oropharyngeal Cancer: The Development of a Decision Aid for Resectable Oropharyngeal Carcinoma, a Mixed Methods Study
Authors: Anne N. Heirman, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Michiel W.M. van den Brekel
Abstract:
Background: Due to the rising incidence of oropharyngeal squamous cell cancer (OPSCC), many patients are challenged with choosing between transoral(robotic) surgery and radiotherapy, with equal survival and oncological outcomes. Also, functional outcomes are of little difference over the years. With this study, the wants and needs of patients and caregivers are identified to develop a comprehensible patient decision aid (PDA). Methods: The development of this PDA is based on the International Patient Decision Aid Standards criteria. In phase 1, relevant literature was reviewed and compared to current counseling papers. We interviewed ten post-treatment patients and ten doctors from four head and neck centers in the Netherlands, which were transcribed verbatim and analyzed. With these results, the first draft of the PDA was developed. Phase 2 beholds testing the first draft for comprehensibility and usability. Phase 3 beholds testing for feasibility. After this phase, the final version of the PDA was developed. Results: All doctors and patients agreed a PDA was needed. Phase 1 showed that 50% of patients felt well-informed after standard care and 35% missed information about treatment possibilities. Side effects and functional outcomes were rated as the most important for decision-making. With this information, the first version was developed. Doctors and patients stated (phase 2) that they were satisfied with the comprehensibility and usability, but there was too much text. The PDA underwent text reduction revisions and got more graphics. After revisions, all doctors found the PDA feasible and would contribute to regular counseling. Patients were satisfied with the results and wished they would have seen it before their treatment. Conclusion: Decision-making for OPSCC should focus on differences in side-effects and functional outcomes. Patients and doctors found the PDA to be of great value. Future research will explore the benefits of the PDA in clinical practice.Keywords: head-and-neck oncology, oropharyngeal cancer, patient decision aid, development, shared decision making
Procedia PDF Downloads 144590 Identification and Quantification of Sesquiterpene Lactones of Sagebrush (Artemisia tridentate) and Its Chemical Modification
Authors: Rosemary Anibogwu, Kavita Sharma, Karl De Jesus
Abstract:
Sagebrush is an abundant and naturally occurring plant in the Intermountain West region of the United States. The plant contains an array of bioactive compounds such as flavonoids, terpenoids, sterols, and phenolic acids. It is important to identify and characterize these compounds because Native Americans use sagebrush as herbal medicine. These compounds are also utilized for preventing infection in wounds, treating headaches and colds, and possess antitumor properties. This research is an exploratory study on the sesquiterpene present in the leaves of sagebrush. The leaf foliage was extracted with 100 % chloroform and 100 % methanol. The percentage yield for the crude was considerably higher in chloroform. The Thin Layer Chromatography (TLC) analysis of the crude extracted unveiled a brown band at Rf = 0.25 and a dark brown band at Rf = 0.74, along with three unknown faint bands the 254 nm UV lamp. Furthermore, the two distinct brown (Achillin) and dark brown band (Hydroxyachillin) in TLC were further utilized in the isolation of pure compounds with column chromatography. The structures of Achillin and Hydroxyachillin were elucidated based on extensive spectroscopic analysis, including TLC, High-Performance Liquid Chromatography (HPLC), 1D- and 2D-Nuclear Magnetic Resonance (NMR), and Mass Spectroscopy (MS). The antioxidant activities of crude extract and three pure compounds were evaluated in terms of their peroxyl radical scavenging by Ferric Reducing Ability of Plasma (FRAP) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude extract showed the antioxidant activity of 18.99 ± 0.51 µmol TEg -1 FW for FRAP and 11.59 ± 0.38 µmol TEg -1 FW for DPPH. The activities of Achillin, Hydroxyachillin, and Quercetagetin trimethyl ether were 13.03, 15.90 and 14.02 µmol TEg -1 FW respectively for the FRAP assay. The three purified compounds have been submitted to the National Cancer Institute 60 cancer cell line for further study.Keywords: HPLC, nuclear magnetic resonance spectroscopy, sagebrush, sesquiterpene lactones
Procedia PDF Downloads 131589 Combined PV Cooling and Nighttime Power Generation through Smart Thermal Management of Photovoltaic–Thermoelectric Hybrid Systems
Authors: Abdulrahman M. Alajlan, Saichao Dang, Qiaoqiang Gan
Abstract:
Photovoltaic (PV) cells, while pivotal for solar energy harnessing, confront a challenge due to the presence of persistent residual heat. This thermal energy poses significant obstacles to the performance and longevity of PV cells. Mitigating this thermal issue is imperative, particularly in tropical regions where solar abundance coexists with elevated ambient temperatures. In response, a sustainable and economically viable solution has been devised, incorporating water-passive cooling within a Photovoltaic-Thermoelectric (PV-TEG) hybrid system to address PV cell overheating. The implemented system has significantly reduced the operating temperatures of PV cells, achieving a notable reduction of up to 15 °C below the temperature observed in standalone PV systems. In addition, a thermoelectric generator (TEG) integrated into the system significantly enhances power generation, particularly during nighttime operation. The developed hybrid system demonstrates its capability to generate power at a density of 0.5 Wm⁻² during nighttime, which is sufficient to concurrently power multiple light-emitting diodes, demonstrating practical applications for nighttime power generation. Key findings from this research include a consistent temperature reduction exceeding 10 °C for PV cells, translating to a 5% average enhancement in PV output power compared to standalone PV systems. Experimental demonstrations underscore nighttime power generation of 0.5 Wm⁻², with the potential to achieve 0.8 Wm⁻² through simple geometric optimizations. The optimal cooling of PV cells is determined by the volume of water in the heat storage unit, exhibiting an inverse relationship with the optimal performance for nighttime power generation. Furthermore, the TEG output effectively powers a lighting system with up to 5 LEDs during the night. This research not only proposes a practical solution for maximizing solar radiation utilization but also charts a course for future advancements in energy harvesting technologies.Keywords: photovoltaic-thermoelectric systems, nighttime power generation, PV thermal management, PV cooling
Procedia PDF Downloads 84588 Debris Flow Mapping Using Geographical Information System Based Model and Geospatial Data in Middle Himalayas
Authors: Anand Malik
Abstract:
The Himalayas with high tectonic activities poses a great threat to human life and property. Climate change is another reason which triggering extreme events multiple fold effect on high mountain glacial environment, rock falls, landslides, debris flows, flash flood and snow avalanches. One such extreme event of cloud burst along with breach of moraine dammed Chorabri Lake occurred from June 14 to June 17, 2013, triggered flooding of Saraswati and Mandakini rivers in the Kedarnath Valley of Rudraprayag district of Uttrakhand state of India. As a result, huge volume of water with its high velocity created a catastrophe of the century, which resulted into loss of large number of human/animals, pilgrimage, tourism, agriculture and property. Thus a comprehensive assessment of debris flow hazards requires GIS-based modeling using numerical methods. The aim of present study is to focus on analysis and mapping of debris flow movements using geospatial data with flow-r (developed by team at IGAR, University of Lausanne). The model is based on combined probabilistic and energetic algorithms for the assessment of spreading of flow with maximum run out distances. Aster Digital Elevation Model (DEM) with 30m x 30m cell size (resolution) is used as main geospatial data for preparing the run out assessment, while Landsat data is used to analyze land use land cover change in the study area. The results of the study area show that model can be applied with great accuracy as the model is very useful in determining debris flow areas. The results are compared with existing available landslides/debris flow maps. ArcGIS software is used in preparing run out susceptibility maps which can be used in debris flow mitigation and future land use planning.Keywords: debris flow, geospatial data, GIS based modeling, flow-R
Procedia PDF Downloads 273587 Murine Pulmonary Responses after Sub-Chronic Exposure to Environmental Ultrafine Particles
Authors: Yara Saleh, Sebastien Antherieu, Romain Dusautoir, Jules Sotty, Laurent Alleman, Ludivine Canivet, Esperanza Perdrix, Pierre Dubot, Anne Platel, Fabrice Nesslany, Guillaume Garcon, Jean-Marc Lo-Guidice
Abstract:
Air pollution is one of the leading causes of premature death worldwide. Among air pollutants, particulate matter (PM) is a major health risk factor, through the induction of cardiopulmonary diseases and lung cancers. They are composed of coarse, fine and ultrafine particles (PM10, PM2.5, and PM0.1 respectively). Ultrafine particles are emerging unregulated pollutants that might have greater toxicity than larger particles, since they are more abundant and consequently have higher surface area per unit of mass. Our project aims to develop a relevant in vivo model of sub-chronic exposure to atmospheric particles in order to elucidate the specific respiratory impact of ultrafine particles compared to fine particulate matter. Quasi-ultrafine (PM0.18) and fine (PM2.5) particles have been collected in the urban industrial zone of Dunkirk in north France during a 7-month campaign, and submitted to physico-chemical characterization. BALB/c mice were then exposed intranasally to 10µg of PM0.18 or PM2.5 3 times a week. After 1 or 3-month exposure, broncho alveolar lavages (BAL) were performed and lung tissues were harvested for histological and transcriptomic analyses. The physico-chemical study of the collected particles shows that there is no major difference in elemental and surface chemical composition between PM0.18 and PM2.5. Furthermore, the results of the cytological analyses carried out show that both types of particulate fractions can be internalized in lung cells. However, the cell count in BAL and preliminary transcriptomic data suggest that PM0.18 could be more reactive and induce a stronger lung inflammation in exposed mice than PM2.5. Complementary studies are in progress to confirm these first data and to identify the metabolic pathways more specifically associated with the toxicity of ultrafine particles.Keywords: environmental pollution, lung affect, mice, ultrafine particles
Procedia PDF Downloads 239586 New Roles of Telomerase and Telomere-Associated Proteins in the Regulation of Telomere Length
Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng
Abstract:
Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.Keywords: aging, hTERT, telomerase, telomeres, human cells
Procedia PDF Downloads 427585 Field Prognostic Factors on Discharge Prediction of Traumatic Brain Injuries
Authors: Mohammad Javad Behzadnia, Amir Bahador Boroumand
Abstract:
Introduction: Limited facility situations require allocating the most available resources for most casualties. Accordingly, Traumatic Brain Injury (TBI) is the one that may need to transport the patient as soon as possible. In a mass casualty event, deciding when the facilities are restricted is hard. The Extended Glasgow Outcome Score (GOSE) has been introduced to assess the global outcome after brain injuries. Therefore, we aimed to evaluate the prognostic factors associated with GOSE. Materials and Methods: In a multicenter cross-sectional study conducted on 144 patients with TBI admitted to trauma emergency centers. All the patients with isolated TBI who were mentally and physically healthy before the trauma entered the study. The patient’s information was evaluated, including demographic characteristics, duration of hospital stays, mechanical ventilation on admission laboratory measurements, and on-admission vital signs. We recorded the patients’ TBI-related symptoms and brain computed tomography (CT) scan findings. Results: GOSE assessments showed an increasing trend by the comparison of on-discharge (7.47 ± 1.30), within a month (7.51 ± 1.30), and within three months (7.58 ± 1.21) evaluations (P < 0.001). On discharge, GOSE was positively correlated with Glasgow Coma Scale (GCS) (r = 0.729, P < 0.001) and motor GCS (r = 0.812, P < 0.001), and inversely with age (r = −0.261, P = 0.002), hospitalization period (r = −0.678, P < 0.001), pulse rate (r = −0.256, P = 0.002) and white blood cell (WBC). Among imaging signs and trauma-related symptoms in univariate analysis, intracranial hemorrhage (ICH), interventricular hemorrhage (IVH) (P = 0.006), subarachnoid hemorrhage (SAH) (P = 0.06; marginally at P < 0.1), subdural hemorrhage (SDH) (P = 0.032), and epidural hemorrhage (EDH) (P = 0.037) were significantly associated with GOSE at discharge in multivariable analysis. Conclusion: Our study showed some predictive factors that could help to decide which casualty should transport earlier to a trauma center. According to the current study findings, GCS, pulse rate, WBC, and among imaging signs and trauma-related symptoms, ICH, IVH, SAH, SDH, and EDH are significant independent predictors of GOSE at discharge in TBI patients.Keywords: field, Glasgow outcome score, prediction, traumatic brain injury.
Procedia PDF Downloads 75584 Pegylated Liposomes of Trans Resveratrol, an Anticancer Agent, for Enhancing Therapeutic Efficacy and Long Circulation
Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh
Abstract:
Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes
Procedia PDF Downloads 589583 Study of the Energy Efficiency of Buildings under Tropical Climate with a View to Sustainable Development: Choice of Material Adapted to the Protection of the Environment
Authors: Guarry Montrose, Ted Soubdhan
Abstract:
In the context of sustainable development and climate change, the adaptation of buildings to the climatic context in hot climates is a necessity if we want to improve living conditions in housing and reduce the risks to the health and productivity of occupants due to thermal discomfort in buildings. One can find a wide variety of efficient solutions but with high costs. In developing countries, especially tropical countries, we need to appreciate a technology with a very limited cost that is affordable for everyone, energy efficient and protects the environment. Biosourced insulation is a product based on plant fibers, animal products or products from recyclable paper or clothing. Their development meets the objectives of maintaining biodiversity, reducing waste and protecting the environment. In tropical or hot countries, the aim is to protect the building from solar thermal radiation, a source of discomfort. The aim of this work is in line with the logic of energy control and environmental protection, the approach is to make the occupants of buildings comfortable, reduce their carbon dioxide emissions (CO2) and decrease their energy consumption (energy efficiency). We have chosen to study the thermo-physical properties of banana leaves and sawdust, especially their thermal conductivities, direct measurements were made using the flash method and the hot plate method. We also measured the heat flow on both sides of each sample by the hot box method. The results from these different experiences show that these materials are very efficient used as insulation. We have also conducted a building thermal simulation using banana leaves as one of the materials under Design Builder software. Air-conditioning load as well as CO2 release was used as performance indicator. When the air-conditioned building cell is protected on the roof by banana leaves and integrated into the walls with solar protection of the glazing, it saves up to 64.3% of energy and avoids 57% of CO2 emissions.Keywords: plant fibers, tropical climates, sustainable development, waste reduction
Procedia PDF Downloads 182582 Inhalable Lipid-Coated-Chitosan Nano-Embedded Microdroplets of an Antifungal Drug for Deep Lung Delivery
Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh
Abstract:
Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design
Procedia PDF Downloads 143581 Computational Elucidation of β-endo-Acetylglucosaminidase (LytB) Inhibition by Kaempferol, Apigenin, and Quercetin in Streptococcus pneumoniae: Anti-Pneumonia Mechanism
Authors: Singh Divya, Rohan Singh, Anjana Pandey
Abstract:
Reviewers' Comments: The study provides valuable insights into the anti-pneumonia properties of flavonoids against LytB. Authors could further validate findings through in vitro studies and consider exploring combination therapies for enhanced efficacy Response: Thankyou for your valuable comments. This study has been conducted further via experimental validation of the in-silico findings. The study uses Streptococcus pneumoniae D39 strain and examine the anti-pneumonia effect of kaempferol, quercetin and apigenin at various concentrations ranging from 9ug/ml to 200ug/ml. From results, it can be concluded that the kaempferol has shown the highest cytotoxic effect (72.1% of inhibition) against S. pneumoniae at concentration of 40ug/ml compare to apigenin and quercetin. The treatment of S. pneumoniae with concoction of kaempferol, quercetin and apigenin has also been performed, it is noted that conc. of 200ug/ml was most effect in achieving 75% inhibition. As S. pneumoniae D39 is a virulent encapsulated strain, the capsule interferes with the uptake of large size drug formulation. For instance, S. pneumoniae D39 with kaempferol and gold nano urchin (GNU) formulation, but the large size of GNU has resulted in reduced cytotoxic effect of kaempferol (27%). To achieve near 100% cytotoxic effect on the MDR S. pneumoniae D39 strain, the study will target the development of kaempferol-engineered gold nano-urchin’ conjugates, where gold nanocrystal will be of small size (less than or equal to 5nm) and decorated with hydroxyl, sulfhydryl, carboxyl, amine and groups. This approach is expected to enhance the anti-pneumonia effect of kaempferol (polyhydroxylated flavonoid). The study will also examine the interactive study among lung epithelial cell line (A549), kaempferol-engineered gold nano urchins, and S. pneumoniae for exploring the colonization, invasion, and biofilm formation of S. pneumoniae on A549 cells resembling the upper respiratory surface of humans.Keywords: streptococcus pneumoniae, β-endo-Acetylglucosaminidase, apigenin, quercetin kaempferol, molecular dynamic simulation, interactome study and GROMACS
Procedia PDF Downloads 2580 Clathrate Hydrate Measurements and Thermodynamic Modelling for Refrigerants with Electrolytes Solution in the Presence of Cyclopentane
Authors: Peterson Thokozani Ngema, Paramespri Naidoo, Amir H. Mohammadi, Deresh Ramjugernath
Abstract:
Phase equilibrium data (dissociation data) for clathrate hydrate (gas hydrate) were undertaken for systems involving fluorinated refrigerants with a single and mixed electrolytes (NaCl, CaCl₂, MgCl₂, and Na₂SO₄) aqueous solution at various salt concentrations in the absence and presence of cyclopentane (CP). The ternary systems for (R410a or R507) with the water system in the presence of CP were performed in the temperature and pressures ranges of (279.8 to 294.4) K and (0.158 to 1.385) MPa, respectively. Measurements for R410a with single electrolyte {NaCl or CaCl₂} solution in the presence of CP were undertaken at salt concentrations of (0.10, 0.15 and 0.20) mass fractions in the temperature and pressure ranges of (278.4 to 293.7) K and (0.214 to1.179) MPa, respectively. The temperature and pressure conditions for R410a with Na₂SO₄ aqueous solution system were investigated at a salt concentration of 0.10 mass fraction in the range of (283.3 to 291.6) K and (0.483 to 1.373) MPa respectively. Measurements for {R410a or R507} with mixed electrolytes {NaCl, CaCl₂, MgCl₂} aqueous solution was undertaken at various salt concentrations of (0.002 to 0.15) mass fractions in the temperature and pressure ranges of (274.5 to 292.9) K and (0.149 to1.119) MPa in the absence and presence of CP, in which there is no published data related to mixed salt and a promoter. The phase equilibrium measurements were performed using a non-visual isochoric equilibrium cell that co-operates the pressure-search technique. This study is focused on obtaining equilibrium data that can be utilized to design and optimize industrial wastewater, desalination process and the development of Hydrate Electrolyte–Cubic Plus Association (HE–CPA) Equation of State. The results show an impressive improvement in the presence of promoter (CP) on hydrate formation because it increases the dissociation temperatures near ambient conditions. The results obtained were modeled using a developed HE–CPA equation of state. The model results strongly agree with the measured hydrate dissociation data.Keywords: association, desalination, electrolytes, promoter
Procedia PDF Downloads 245579 Treatment of Non-Small Cell Lung Cancer (NSCLC) With Activating Mutations Considering ctDNA Fluctuations
Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.
Abstract:
Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis
Procedia PDF Downloads 54578 Synthesis of Highly Stable Multi-Functional Iron Oxide Nanoparticles for Active Mitochondrial Targeting in Immunotherapy
Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour
Abstract:
Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle
Procedia PDF Downloads 74577 Morphology Analysis of Apple-Carrot Juice Treated by Manothermosonication (MTS) and High Temperature Short Time (HTST) Processes
Authors: Ozan Kahraman, Hao Feng
Abstract:
Manothermosonication (MTS), which consists of the simultaneous application of heat and ultrasound under moderate pressure (100-700 kPa), is one of the technologies which destroy microorganisms and inactivates enzymes. Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through an ultra-thin specimen, interacting with the specimen as it passes through it. The environmental scanning electron microscope or ESEM is a scanning electron microscope (SEM) that allows for the option of collecting electron micrographs of specimens that are "wet," uncoated. These microscopy techniques allow us to observe the processing effects on the samples. This study was conducted to investigate the effects of MTS and HTST treatments on the morphology of apple-carrot juices by using TEM and ESEM microscopy. Apple-carrot juices treated with HTST (72 0C, 15 s), MTS 50 °C (60 s, 200 kPa), and MTS 60 °C (30 s, 200 kPa) were observed in both ESEM and TEM microscopy. For TEM analysis, a drop of the solution dispersed in fixative solution was put onto a Parafilm ® sheet. The copper coated side of the TEM sample holder grid was gently laid on top of the droplet and incubated for 15 min. A drop of a 7% uranyl acetate solution was added and held for 2 min. The grid was then removed from the droplet and allowed to dry at room temperature and presented into the TEM. For ESEM analysis, a critical point drying of the filters was performed using a critical point dryer (CPD) (Samdri PVT- 3D, Tousimis Research Corp., Rockville, MD, USA). After the CPD, each filter was mounted onto a stub and coated with gold/palladium with a sputter coater (Desk II TSC Denton Vacuum, Moorestown, NJ, USA). E.Coli O157:H7 cells on the filters were observed with an ESEM (Philips XL30 ESEM-FEG, FEI Co., Eindhoven, The Netherland). ESEM (Environmental Scanning Electron Microscopy) and TEM (Transmission Electron Microscopy) images showed extensive damage for the samples treated with MTS at 50 and 60 °C such as ruptured cells and breakage on cell membranes. The damage was increasing with increasing exposure time.Keywords: MTS, HTST, ESEM, TEM, E.COLI O157:H7
Procedia PDF Downloads 285576 Prevalence of Trichomonas Tenax in Patients with Pulmonary Disease and Watersheds and Its Potential Implications for Pulmonary Virus Infection
Authors: Pei Chi Fang, Wei Chen Lin
Abstract:
Trichomonas tenax is a microaerophilic oral protozoan found in patients with poor oral hygiene. It participates in the inflammatory process of periodontal disease and can potentially be aspirated into the lungs, giving rise to pulmonary trichomoniasis. However, the precise roles of T. tenax in the pulmonary system remain largely unexplored and warrant comprehensive epidemiological investigation. To assess the prevalence of T. tenax infection, we collected bronchoalveolar lavage fluid (BALF) samples from hospitalized patients with lung diseases. A specific nested PCR approach was employed to determine prevalence rates, yielding 21 positive cases out of 61 samples from Ditmanson Medical Foundation Chia-Yi Christian Hospital, and 11 positive cases out of 55 samples from National Cheng Kung University Hospital. Furthermore, there is a critical need for comprehensive data regarding the presence of T. tenax in environmental surface watersheds. In this context, we present findings from investigations in the Yanshuei and Donggang river basins in southern Taiwan, which are crucial sources for public drinking water in the region. In order to elucidate potential implications on pulmonary virus infections, we conducted an analysis of gene expression level changes in H292 cell line after exposure to T. tenax. Our findings revealed significant regulation of multiple virus-related genes, including IFI44L and IFITM3. Ongoing research endeavors are focused on identifying the key components within T. tenax responsible for these observed effects. Crucially, this study lays the groundwork for a preliminary understanding of T. tenax prevalence in patients with pulmonary diseases. It also seeks to establish a meaningful correlation between lung infections and oral hygiene practices, with the ultimate aim of informing distinct treatment and prevention strategies.Keywords: parasitology, genes, virus, human health, infection, lung
Procedia PDF Downloads 71575 Association of Mir-196a Expression in Esophageal Tissue with Barrett´s Esophagus and Esophageal Adenocarcinoma
Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala
Abstract:
Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker
Procedia PDF Downloads 112574 An Enzyme Technology - Metnin™ - Enables the Full Replacement of Fossil-Based Polymers by Lignin in Polymeric Composites
Authors: Joana Antunes, Thomas Levée, Barbara Radovani, Anu Suonpää, Paulina Saloranta, Liji Sobhana, Petri Ihalainen
Abstract:
Lignin is an important component in the exploitation of lignocellulosic biomass. It has been shown that within the next years, the yield of added-value lignin-based chemicals and materials will generate renewable alternatives to oil-based products (e.g. polymeric composites, resins and adhesives) and enhance the economic feasibility of biorefineries. In this paper, a novel technology for lignin valorisation (METNIN™) is presented. METNIN™ is based on the oxidative action of an alkaliphilic enzyme in aqueous alkaline conditions (pH 10-11) at mild temperature (40-50 °C) combined with a cascading membrane operation, yielding a collection of lignin fractions (from oligomeric down to mixture of tri-, di- and monomeric units) with distinct molecular weight distribution, low polydispersity and favourable physicochemical properties. The alkaline process conditions ensure the high processibility of crude lignin in an aqueous environment and the efficiency of the enzyme, yielding better compatibility of lignin towards targeted applications. The application of a selected lignin fraction produced by METNIN™ as a suitable lignopolyol to completely replace a commercial polyol in polyurethane rigid foam formulations is presented as a prototype. Liquid lignopolyols with a high lignin content were prepared by oxypropylation and their full utilization in the polyurethane rigid foam formulation was successfully demonstrated. Moreover, selected technical specifications of different foam demonstrators were determined, including closed cell count, water uptake and compression characteristics. These specifications are within industrial standards for rigid foam applications. The lignin loading in the lignopolyol was a major factor determining the properties of the foam. In addition to polyurethane foam demonstrators, other examples of lignin-based products related to resins and sizing applications will be presented.Keywords: enzyme, lignin valorisation, polyol, polyurethane foam
Procedia PDF Downloads 153573 Poly(L-Lactic Acid) Scaffolds for Bone Tissue Engineering
Authors: Aleksandra BužArovska, Gordana Bogoeva Gaceva
Abstract:
Biodegradable polymers have received significant scientific attention in tissue engineering (TE) application, in particular their composites consisting of inorganic nanoparticles. In the last 15 years, they are subject of intensive research by many groups, aiming to develop polymer scaffolds with defined biodegradability, porosity and adequate mechanical stability. The most important characteristic making these materials attractive for TE is their biodegradability, a process that could be time controlled and long enough to enable generation of a new tissue as a replacement for the degraded polymer scaffold. In this work poly(L-lactic acid) scaffolds, filled with TiO2 nanoparticles functionalized with oleic acid, have been prepared by thermally induced phase separation method (TIPS). The functionalization of TiO2 nanoparticles with oleic acid was performed in order to improve the nanoparticles dispersibility within the polymer matrix and at the same time to inhibit the cytotoxicity of the nanofiller. The oleic acid was chosen as amphiphilic molecule belonging to the fatty acid family because of its non-toxicity and possibility for mediation between the hydrophilic TiO2 nanoparticles and hydrophobic PLA matrix. The produced scaffolds were characterized with thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and mechanical compression measurements. The bioactivity for bone tissue engineering application was tested in supersaturated simulated body fluid. The degradation process was followed by Fourier transform infrared spectroscopy (FTIR). The results showed anisotropic morphology with elongated open pores (100 µm), high porosity (around 92%) and perfectly dispersed nanofiller. The compression moduli up to 10 MPa were identified independent on the nanofiller content. Functionalized TiO2 nanoparticles induced formation of hydroxyapatite clusters as much as unfunctionalized TiO2. The prepared scaffolds showed properties ideal for scaffold vascularization, cell attachment, growth and proliferation.Keywords: biodegradation, bone tissue engineering, mineralization, PLA scaffolds
Procedia PDF Downloads 269572 Multidimensional Poverty and Its Correlates among Rural Households in Limpopo Province, South Africa
Authors: Tamunotonye Mayowa Braide, Isaac Oluwatayo
Abstract:
This study investigates multidimensional poverty, and its correlates among rural households in Sekhukhune and Capricorn District municipalities (SDM & CDM) in Limpopo Province, South Africa. Primary data were collected from 407 rural households selected through purposive and simple random sampling techniques. Analytical techniques employed include descriptive statistics, principal component analysis (PCA), and the Alkire Foster (A-F) methodology. The results of the descriptive statistics showed there are more females (66%) than males (34%) in rural areas of Limpopo Province, with about 45% of them having secondary school education as the highest educational level attained and only about 3% do not have formal education. In the analysis of deprivation, eight dimensions of deprivation, constructed from 21 variables, were identified using the PCA. These dimensions include type and condition of dwelling water and sanitation, educational attainment and income, type of fuel for cooking and heating, access to clothing and cell phone, assets and fuel for light, health condition, crowding, and child health. In identifying the poor with poverty cut-off (0.13) of all indicators, about 75.9% of the rural households are deprived in 25% of the total dimensions, with the adjusted headcount ratio (M0) being 0.19. Multidimensional poverty estimates showed higher estimates of poor rural households with 71%, compared to 29%, which fall below the income poverty line. The study conducted poverty decomposition, using sub-groups within the area by examining regions and household characteristics. In SDM, there are more multidimensionally poor households than in CDM. The water and sanitation dimension is the largest contributor to the multidimensional poverty index (MPI) in rural areas of Limpopo Province. The findings can, therefore, assist in better design of welfare policy and target poverty alleviation programs and as well help in efficient resource allocation at the provincial and local municipality levels.Keywords: Alkire-Foster methodology, Limpopo province, multidimensional poverty, principal component analysis, South Africa
Procedia PDF Downloads 164571 Molecular Docking Study of Rosmarinic Acid and Its Analog Compounds on Sickle Cell Hemoglobin
Authors: Roohallah Yousefi
Abstract:
Introduction: Voxelotor, also known as GBT 440, binds to the alpha cleft in HbS tetramers and promotes the stability of the relaxed or oxygenated state of HbS. This process hinders the conformational change of the HbS tetramers into the deoxygenated state. Voxelotor prevents interactions between HbS tetramers in the deoxygenated state, ultimately inhibiting the polymerization of HbS tetramers and resulting in significant clinical improvements, particularly in raising hemoglobin levels in patients. In this study, we have explored the use of herbal compound models, such as rosmarinic acid and compounds with similar structures that exhibit high binding affinity to Voxelotor's hemoglobin binding site. Materials and methods: The molecular model of hemoglobin (PDB: 5E83) was initially obtained from the RCSB PDB database. In addition, we collected 453 ligand models with structural similarity to rosmarinic acid from the PubChem database. To prepare these models for molecular docking, we utilized the Molegro Virtual Docker tool. Subsequently, we used the SwissADME web tool to predict the physicochemical properties and pharmacokinetics of these compounds. Results: We investigated the affinity and binding site of 453 compounds similar to rosmarinic acid on the hemoglobin model (PDB: 5E83). Our focus was on the alpha cleft between two alpha chains of the hemoglobin model (PDB: 5E83). The results showed that most compounds had molecular weights above 500 daltons, and some exhibited acceptable hydrophobicity. Furthermore, their solubility in aqueous solutions was good. None of the compounds were able to cross the blood-brain barrier or have gastrointestinal absorption. However, they did have varying inhibitory effects on CYP2C9 cytochromes. The skin penetration rate was generally low. Conclusion: Through our study, we identified three compounds (CID: 162739375, CID: 141386569, and CID: 24015539) with promising potential for further research. These compounds demonstrated high binding affinity to the hemoglobin model, favorable dissolution and digestive absorption rates, as well as suitable hydrophobicity, making them ideal candidates for continued laboratory investigation.Keywords: voxelotor, binding site, hemoglobin, rosmarinic acid
Procedia PDF Downloads 8570 Optical Simulation of HfO₂ Film - Black Silicon Structures for Solar Cells Applications
Authors: Gagik Ayvazyan, Levon Hakhoyan, Surik Khudaverdyan, Laura Lakhoyan
Abstract:
Black Si (b-Si) is a nano-structured Si surface formed by a self-organized, maskless process with needle-like surfaces discernible by their black color. The combination of low reflectivity and the semi-conductive properties of Si found in b-Si make it a prime candidate for application in solar cells as an antireflection surface. However, surface recombination losses significantly reduce the efficiency of b-Si solar cells. Surface passivation using suitable dielectric films can minimize these losses. Nowadays some works have demonstrated that excellent passivation of b-Si nanostructures can be reached using Al₂O₃ films. However, the negative fixed charge present in Al₂O₃ films should provide good field effect passivation only for p- and p+-type Si surfaces. HfO2 thin films have not been practically tested for passivation of b-Si. HfO₂ could provide an alternative for n- and n+- type Si surface passivation since it has been shown to exhibit positive fixed charge. Using optical simulation by Finite-Difference Time Domain (FDTD) method, the possibility of b-Si passivation by HfO2 films has been analyzed. The FDTD modeling revealed that b-Si layers with HfO₂ films effectively suppress reflection in the wavelength range 400–1000 nm and across a wide range of incidence angles. The light-trapping performance primarily depends on geometry of the needles and film thickness. With the decrease of periodicity and increase of height of the needles, the reflectance decrease significantly, and the absorption increases significantly. Increase in thickness results in an even greater decrease in the calculated reflection coefficient of model structures and, consequently, to an improvement in the antireflection characteristics in the visible range. The excellent surface passivation and low reflectance results prove the potential of using the combination of the b-Si surface and the HfO₂ film for solar cells applications.Keywords: antireflection, black silicon, HfO₂, passivation, simulation, solar cell
Procedia PDF Downloads 146569 Isolation and Characterization of the First Known Inhibitor Cystine Knot Peptide in Sea Anemone: Inhibitory Activity on Acid-Sensing Ion Channels
Authors: Armando A. Rodríguez, Emilio Salceda, Anoland Garateix, André J. Zaharenko, Steve Peigneur, Omar López, Tirso Pons, Michael Richardson, Maylín Díaz, Yasnay Hernández, Ludger Ständker, Jan Tytgat, Enrique Soto
Abstract:
Acid-sensing ion channels are cation (Na+) channels activated by a pH drop. These proteins belong to the ENaC/degenerin superfamily of sodium channels. ASICs are involved in sensory perception, synaptic plasticity, learning, memory formation, cell migration and proliferation, nociception, and neurodegenerative disorders, among other processes; therefore those molecules that specifically target these channels are of growing pharmacological and biomedical interest. Sea anemones produce a large variety of ion channels peptide toxins; however, those acting on ligand-gated ion channels, such as Glu-gated, Ach-gated ion channels, and acid-sensing ion channels (ASICs), remain barely explored. The peptide PhcrTx1 is the first compound characterized from the sea anemone Phymanthus crucifer, and it constitutes a novel ASIC inhibitor. This peptide was purified by chromatographic techniques and pharmacologically characterized on acid-sensing ion channels of mammalian neurons using patch-clamp techniques. PhcrTx1 inhibited ASIC currents with an IC50 of 100 nM. Edman degradation yielded a sequence of 32 amino acids residues, with a molecular mass of 3477 Da by MALDI-TOF. No similarity to known sea anemone peptides was found in protein databases. The computational analysis of Cys-pattern and secondary structure arrangement suggested that this is a structurally ICK (Inhibitor Cystine Knot)-type peptide, a scaffold that had not been found in sea anemones but in other venomous organisms. These results show that PhcrTx1 represents the first member of a new structural group of sea anemones toxins acting on ASICs. Also, this peptide constitutes a novel template for the development of drugs against pathologies related to ASICs function.Keywords: animal toxin, inhibitor cystine knot, ion channel, sea anemone
Procedia PDF Downloads 310