Search results for: myostatin signaling pathway

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

Abstract:

Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

Procedia PDF Downloads 433

Authors: Henry Memczak, Marc Hovestaedt, Bernhard Ay, Sandra Saenger, Thorsten Wolff, Frank F. Bier

Abstract:

The influenza viruses cause flu epidemics every year and serious pandemics in larger time intervals. The only cost-effective protection against influenza is vaccination. Due to rapid mutation continuously new subtypes appear, what requires annual reimmunization. For a correct vaccination recommendation, the circulating influenza strains had to be detected promptly and exactly and characterized due to their antigenic properties. During the flu season 2016/17, a wrong vaccination recommendation has been given because of the great time interval between identification of the relevant influenza vaccine strains and outbreak of the flu epidemic during the following winter. Due to such recurring incidents of vaccine mismatches, there is a great need to speed up the process chain from identifying the right vaccine strains to their administration. The monitoring of subtypes as part of this process chain is carried out by national reference laboratories within the WHO Global Influenza Surveillance and Response System (GISRS). To this end, thousands of viruses from patient samples (e.g., throat smears) are isolated and analyzed each year. Currently, this analysis involves complex and time-intensive (several weeks) animal experiments to produce specific hyperimmune sera in ferrets, which are necessary for the determination of the antigen profiles of circulating virus strains. These tests also bear difficulties in standardization and reproducibility, which restricts the significance of the results. To replace this test a peptide-based assay for influenza virus subtyping from corresponding virus samples was developed. The differentiation of the viruses takes place by a set of specifically designed peptidic recognition molecules which interact differently with the different influenza virus subtypes. The differentiation of influenza subtypes is performed by pattern recognition guided by machine learning algorithms, without any animal experiments. Synthetic peptides are immobilized in multiplex format on various platforms (e.g., 96-well microtiter plate, microarray). Afterwards, the viruses are incubated and analyzed comparing different signaling mechanisms and a variety of assay conditions. Differentiation of a range of influenza subtypes, including H1N1, H3N2, H5N1, as well as fine differentiation of single strains within these subtypes is possible using the peptide-based subtyping platform. Thereby, the platform could be capable of replacing the current antigenic characterization of influenza strains using ferret hyperimmune sera.

Keywords: antigenic characterization, influenza-binding peptides, influenza subtyping, influenza surveillance

Procedia PDF Downloads 158

Authors: Ramatu I. Sha’aba, Mathias A. Chia, Abdullahi B. Alhassan, Yisa A. Gana, Ibrahim M. Gadzama

Abstract:

Globally, Diclofenac (DLC) and Ibuprofen (IBU) are the most prescribed drugs due to their antipyretic and analgesic properties. They are, however, highly toxic at elevated doses, with the involvement of an already described oxidative stress pathway. As a result, there is rising concern about the ecological fate of analgesics on non-target organisms such as Daphnia magna and Phytoplankton species. Phytoplankton is a crucial component of the aquatic ecosystem that serves as the primary producer at the base of the food chain. However, the increasing presence and levels of micropollutants such as these analgesics can disrupt their community structure, dynamics, and ecosystem functions. This study presents a comprehensive series of the physiology, antioxidant response, immobilization, and risk assessment of Diclofenac and Ibuprofen’s effects on Daphnia magna and the Phytoplankton community using a laboratory approach. The effect of DLC and IBU at 27.16 µg/L and 20.89 µg/L, respectively, for a single exposure and 22.39 µg/L for combined exposure of DLC and IBU for the experimental setup. The antioxidant response increased with increasing levels of stress. The highest stressor to the organism was 1000 µg/L of DLC and 10,000 µg/L of IBU. Peroxidase and glutathione -S-transferase activity was higher for Diclofenac + Ibuprofen. The study showed 60% and 70% immobilization of the organism at 1000 g L-1 of DLC and IBU. The two drugs and their combinations adversely impacted Phytoplankton biomass with increased exposure time. However, combining the drugs resulted in more significant adverse effects on physiological and pigment content parameters. The risk assessment calculation for the risk quotient and toxic unit of the analgesic reveals from this study was RQ Diclofenac = 8.41, TU Diclofenac = 3.68, and RQ Ibuprofen = 718.05 and TU Ibuprofen = 487.70. Hence, these findings demonstrate that the current exposure concentrations of Diclofenac and Ibuprofen can immobilize D. magna. This study shows the dangers of multiple drugs in the aquatic environment because their combinations could have additive effects on the structure and functions of Phytoplankton and are capable of immobilizing D. magna.

Keywords: algae, analgesic drug, daphnia magna, toxicity

Procedia PDF Downloads 79

Authors: Pascal U. Onu, Doris A. Ogbang, Emmanuel Okechukwu.

Abstract:

Background: Plastics in their various forms have become ubiquitous in a very short space of time. This ubiquitous nature has plagued and daunted nations globally, overwhelming their ability to manage the environmental impact, especially its linkages to climate change. This has mobilized nations globally and triggered debates on the best approaches to ensure sustainability in terms of its production and utilization, as total elimination seems unrealistic. Objective: This study undertook to understand the pattern of plastic waste management, and its pollution awareness levels by the residents of the study area. Methods: Data were obtained through questionnaires designed specifically for plastic waste and qualitatively via journals and articles. Simple descriptive survey techniques with a survey population size of 300 respondents using kobo collect were employed. Results: Analysis based on disaggregated data indicated a proportionate distribution among male and female respondents (53% male and 47% female, respectively). Overall awareness levels on plastic waste's contribution to climate change, compared to its environmental impact, are reflective of a dire need for increased efforts in strengthening awareness creation, especially across gender populations and religious backgrounds. Drainage blockage topped the ranks among common problems caused by plastic waste within the area. Various plastic waste disposal methods were ranked, while pro-environmental measures for reducing the waste menace showed more willingness from males at 52%. Conclusion: These outcomes are instructive and suggest the need for renewed and increased awareness/education on the nexus of plastic pollution to climate change and also appropriate synergies/collaboration between government, private sector, and local communities, especially in the area of recycling to improve sustainability in plastic waste management.

Keywords: plastic waste, KAP, climate change, Nigeria

Procedia PDF Downloads 41

Authors: Parker Murray, Marci Johnson, Tyson S. Burnham, Alina K. Fong, Mark D. Allen, Bruce McIff

Abstract:

Purpose: Pathological dysregulation of Neurovascular Coupling (NVC) caused by mild traumatic brain injury (mTBI) is the predominant source of chronic post-concussion syndrome (PCS) symptomology. fNCI has the ability to localize dysregulation in NVC by measuring blood-oxygen-level-dependent (BOLD) signaling during the performance of fMRI-adapted neuropsychological evaluations. With fNCI, 57 brain areas consistently affected by concussion were identified as PCS neural markers, which were validated on large samples of concussion patients and healthy controls. These neuromarkers provide the basis for a computation of PCS severity which is referred to as the Severity Index Score (SIS). The SIS has proven valuable in making pre-treatment decisions, monitoring treatment efficiency, and assessing long-term stability of outcomes. Methods and Materials: After being scanned while performing various cognitive tasks, 476 concussed patients received an SIS score based on the neural dysregulation of the 57 previously identified brain regions. These scans provide an objective measurement of attentional, subcortical, visual processing, language processing, and executive functioning abilities, which were used as biomarkers for post-concussive neural dysregulation. Initial SIS scores were used to develop individualized therapy incorporating cognitive, occupational, and neuromuscular modalities. These scores were also used to establish pre-treatment benchmarks and measure post-treatment improvement. Results: Changes in SIS were calculated in percent change from pre- to post-treatment. Patients showed a mean improvement of 76.5 percent (σ= 23.3), and 75.7 percent of patients showed at least 60 percent improvement. Longitudinal reassessment of 24 of the patients, measured an average of 7.6 months post-treatment, shows that SIS improvement is maintained and improved, with an average of 90.6 percent improvement from their original scan. Conclusions: fNCI provides a reliable measurement of NVC allowing for identification of concussion pathology. Additionally, fNCI derived SIS scores direct tailored therapy to restore NVC, subsequently resolving chronic PCS resulting from mTBI.

Keywords: concussion, functional magnetic resonance imaging (fMRI), neurovascular coupling (NVC), post-concussion syndrome (PCS)

Procedia PDF Downloads 359

Authors: Hannes Groeneweg

Abstract:

Myanmar is considered one of the largest fishing nations in the world. The country’s rapid economic and political reform process since 2011 entails both challenges and opportunities for its marine fishing sector. The development pathway of the sector remains unclear. Which future will eventually materialize is shaped and determined by the various visions and actions of the stakeholders engaging in political debates and decision-making. These visions can be conceptualized through the Science and Technology Studies (STS) concept of sociotechnical imaginaries. The research of this article is guided by the question of which imaginaries are currently relevant, who is propagating these imaginaries, and how are these imaginaries produced and contested. Using qualitative documentary analysis of policy documents, reports, and media articles as well as in-depth interviews with key stakeholders, three archetypical national sociotechnical imaginaries of Myanmar’s future marine fisheries were identified: The industrial scale extractivism imaginary views marine fishing sector as a driver for national economic growth and focuses on the industrial and technological development of the production chain, increasing yield and exports. Sustainable fishing management encompasses the vulnerability of marine ecosystems and views increasing efficient sustainability governance, planning, and management into existing fishing practices. In the traditional sufficiency fishing imaginary, small-scale fishing practices are viewed as an important livelihood practice for millions of coastal dwellers. The need to conserve them through strengthening the self-reliance, autonomy, and resilience of these communities is stressed. In national debates, the first two imaginaries are currently dominant. The imaginaries, as well as their contestations, are also linked to other critical political issues. The paper suggests that participatory decision-making processes are needed to create an inclusive imaginary of the future marine fishing sector.

Keywords: science and technology studies, sociotechnical imaginaries, marine fishing, knowledge coproduction, Myanmar

Procedia PDF Downloads 181

Authors: Parisa Afshin, Terje Grønning

Abstract:

Norway, similar to many other countries, has set the focus of its policies in creating new strong and highly innovative sectors in recent years, as the oil and gas sector profitability is declining. Biotechnology sector in Norway has a great potential, especially in marine-biotech and cancer medicine. However, Norway being a periphery faces especial challenges in the path of creating internationally well-known biotech sector and an international knowledge hub. The aim of this article is to analyze the progress of the Norwegian biotechnology industry, its pathway to build up an innovation network and conduct collaborative innovation based on its initial conditions and its own advantage and disadvantages. The findings have important implications not only for politicians and academic in understanding the infrastructure of biotechnology sector in the country, but it has important lessons for other periphery countries or regions aiming in creating strong biotechnology sector and catching up with the strong internationally-recognized regions. Data and methodology: To achieve the main goal of this study, information has been collected via secondary resources such as web pages and annual reports published by the officials and mass media along with interviews were used. The data were collected with the goal to shed light on a brief history and current status of Norway biotechnology sector, as well as geographic distribution of biotech industry, followed by the role of academic and industry collaboration and public policies in Norway biotech. As knowledge is the key input in innovation, knowledge perspective of the system such as knowledge flow in the sector regarding the national and regional innovation system has been studied. Primary results: The internationalization has been an important element in development of periphery regions' innovativeness enabling them to overcome their weakness while putting more weight on the importance of regional policies. Following such findings, suggestions on policy decision and international collaboration, regarding national and regional system of innovation, has been offered as means of promoting strong innovative sector.

Keywords: biotechnology sector, knowledge-based industry, national innovation system, regional innovation system

Procedia PDF Downloads 226

Authors: M. G. Cattaneo

Abstract:

The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: global health, global justice, patent law reform, access to drugs

Procedia PDF Downloads 246

Authors: Parvaneh Mahmoudi, Ahmad Moeni, Seyed Mojtaba Khayam Nekoei, Mohsen Mardi, Mehrshad Zeinolabedini, Ghasem Hosseini Salekdeh

Abstract:

Saffron (Crocus sativus L.) is one of the most important spice and medicinal plants. The three-branch style of C. sativus flowers are the most important economic part of the plant and known as saffron, which has several medicinal properties. Despite the economic and biological significance of this plant, knowledge about its molecular characteristics is very limited. In the present study, we, for the first time, constructed a comprehensive dataset for C. sativus stigma through de novo transcriptome sequencing. We performed de novo transcriptome sequencing of C. sativus stigma using the Illumina paired-end sequencing technology. A total of 52075128 reads were generated and assembled into 118075 unigenes, with an average length of 629 bp and an N50 of 951 bp. A total of 66171unigenes were identified, among them, 66171 (56%) were annotated in the non-redundant National Center for Biotechnology Information (NCBI) database, 30938 (26%) were annotated in the Swiss-Prot database, 10273 (8.7%) unigenes were mapped to 141 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, while 52560 (44%) and 40756 (34%) unigenes were assigned to Gen Ontology (GO) categories and Eukaryotic Orthologous Groups of proteins (KOG), respectively. In addition, 65 candidate genes involved in three stages of crocin biosynthesis were identified. Finally, transcriptome sequencing of saffron stigma was used to identify 6779 potential microsatellites (SSRs) molecular markers. High-throughput de novo transcriptome sequencing provided a valuable resource of transcript sequences of C. sativus in public databases. In addition, most of candidate genes potentially involved in crocin biosynthesis were identified which could be further utilized in functional genomics studies. Furthermore, numerous obtained SSRs might contribute to address open questions about the origin of this amphiploid spices with probable little genetic diversity.

Keywords: saffron, transcriptome, NGS, bioinformatic

Procedia PDF Downloads 102

Authors: Lejla Sunagic

Abstract:

The aim of the manuscript is to further the understanding of risky decision-making in the context of forced and irregular migration. The empirical evidence is collected through interviews with Syrian refugees who arrived in Europe via irregular pathways. Analytically, it has been approached through the juxtaposition between risk perception and the notion of desire. As different frameworks have been developed to address differences in risk perception, the common thread was the understanding that individual risk-taking has been addressed in terms of benefits outweighing risks. However, this framework cannot explain a big risk an individual takes because of an underprivileged position and due to a lack of positive alternatives, termed as risk-taking from vulnerability. The accounts of the field members of this study that crossed the sea in rubber boats to arrive in Europe make an empirical fit to such a postulate by reporting that the risk they have taken was not the choice but the only coping strategy. However, the vulnerability argument falls short of explaining why the interviewees, thinking retrospectively, find the risky journey they have taken to be worth it, while they would strongly advise others to restrain from taking such a huge risk. This inconsistency has been addressed by adding the notion of desire to migrate to the elements of risk perception. Desire, as a subjective experience, was what made the risk appear smaller in cost-benefit analysis at the time of decision-making of those who have realized migration. However, when they reflect on others in the context of potential migration via the same pathway, the interviewees addressed the others’ lack of capacity to avoid the same obstacles that they themselves were able to circumvent while omitting to reflect on others’ desire to migrate. Thus, in the risk-benefit analysis performed for others, the risk remains unblurred and tips over the benefits, given the inability to take into account the desire of others. If desire, as the transformative potential of migration, is taken out of the cost-benefit analysis of irregular migration, refugees might not have taken the risky journey. By casting the theoretical argument in the language of configuration, the study is filling in the gap of knowledge on the combination of migration drivers and the way they interact and produce migration outcomes.

Keywords: refugees, risk perception, desire, irregular migration

Procedia PDF Downloads 97

Authors: W. Thongkham, K. Sinthiptharakoon, K. Tantisantisom, A. Klamchuen, P. Khanchaitit, K. Jiramitmongkon, C. Lertsatitthanakorn, M. Liangruksa

Abstract:

Due to demands of sustainable energy, thermoelectricity converting waste heat into electrical energy has become one of the intensive fields of worldwide research. However, such harvesting technology has shown low device performance in the temperature range below 150℃. In this work, a hybrid nanowire of inorganic bismuth telluride (Bi₂Te₃) and organic poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) synthesized using a simple in-situ one-pot synthesis, enhancing efficiency of the nanowire-incorporated PEDOT:PSS-based thermoelectric converter is highlighted. Since the improvement is ascribed to the increased electrical conductivity of the thermoelectric host material, the individual hybrid nanowires are investigated using voltage-dependent conductive atomic force microscopy (CAFM) and spectroscopy (CAFS) considering that the electrical transport measurement can be performed either on insulating or conducting areas of the sample. Correlated with detailed chemical information on the crystalline structure and compositional profile of the nanowire core-shell structure, an electrical transporting pathway through the nanowire and the corresponding electronic-band structure have been determined, in which the native oxide layer on the Bi₂Te₃ surface is not considered, and charge conduction on the topological surface states of Bi₂Te₃ is suggested. Analyzing the core-shell nanowire synthesized using the conventional mixing of as-prepared Bi₂Te₃ nanowire with PEDOT:PSS for comparison, the oxide-removal effect of the in-situ encapsulating polymeric layer is further supported. The finding not only provides a structural information for mechanistic determination of the thermoelectricity, but it also encourages new approach toward more appropriate encapsulation and consequently higher efficiency of the nanowire-based thermoelectric generation.

Keywords: electrical transport measurement, hybrid Bi₂Te₃-PEDOT:PSS nanowire, nanoencapsulation, thermoelectricity, topological insulator

Procedia PDF Downloads 205

Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

Abstract:

Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

Procedia PDF Downloads 379

Authors: Sher Ali

Abstract:

Organic agriculture has gained significant momentum globally as a sustainable and environmentally friendly farming practice. In Pakistan, amidst growing concerns about food security, environmental degradation, and health issues related to conventional farming methods, the adoption of organic agriculture presents a promising pathway for agricultural development. This abstract aims to provide an overview of the status, opportunities, challenges, and future directions of organic agriculture in Pakistan. It delves into the current state of organic farming practices, including the extent of adoption, key crops cultivated, and the regulatory framework governing organic certification. Furthermore, the abstract discusses the unique opportunities that Pakistan offers for organic agriculture, such as its diverse agro-climatic zones, rich biodiversity, and traditional farming knowledge. It highlights successful initiatives and case studies that showcase the potential of organic farming to improve rural livelihoods, enhance food security, and promote sustainable agricultural practices. However, the abstract also addresses the challenges hindering the widespread adoption of organic agriculture in Pakistan, ranging from limited awareness and technical know-how among farmers to inadequate infrastructure and market linkages. It emphasizes the need for supportive policies, capacity-building programs, and investment in research and extension services to overcome these challenges and promote the growth of the organic agriculture sector. Lastly, the abstract outlines future directions and recommendations for advancing organic agriculture in Pakistan, including strategies for scaling up production, strengthening certification mechanisms, and fostering collaboration among stakeholders. By shedding light on the opportunities, challenges, and potential of organic agriculture in Pakistan, this abstract aims to contribute to the discourse on sustainable farming practices at the upcoming Agro Conference in the USA. It invites participants to engage in dialogue, share experiences, and explore avenues for collaboration toward promoting organic agriculture for a healthier, more resilient food system.

Keywords: agriculture, challenges, organic, Pakistan

Procedia PDF Downloads 54

Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

Abstract:

Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

Procedia PDF Downloads 441

Authors: Ketaki D. Belsare, Nicholas F. Polizzi, Lior Shtayer, William F. DeGrado

Abstract:

Nature utilizes metalloproteins to perform chemical transformations with activities and selectivities that have long been the inspiration for design principles in synthetic and biological systems. The chemical reactivities of metalloproteins are directly linked to local environment effects produced by the protein matrix around the metal cofactor. A complete understanding of how the protein matrix provides these interactions would allow for the design of functional metalloproteins. The de novo computational design of proteins have been successfully used in design of active sites that bind metals like di-iron, zinc, copper containing cofactors; however, precisely designing active sites that can bind small molecule ligands (e.g., substrates) along with metal cofactors is still a challenge in the field. The de novo computational design of a functional metalloprotein that contains a purposefully designed substrate binding site would allow for precise control of chemical function and reactivity. Our research strategy seeks to elucidate the design features necessary to bind the cofactor protoporphyrin IX (hemin) in close proximity to a substrate binding pocket in a four helix bundle. First- and second-shell interactions are computationally designed to control orientation, electronic structure, and reaction pathway of the cofactor and substrate. The design began with a parameterized helical backbone that positioned a single histidine residue (as an axial ligand) to receive a second-shell H-bond from a Threonine on the neighboring helix. The metallo-cofactor, hemin was then manually placed in the binding site. A structural feature, pi-bulge was introduced to give substrate access to the protoporphyrin IX. These de novo metalloproteins are currently being tested for their activity towards hydroxylation and epoxidation. The de novo designed protein shows hydroxylation of aniline to 4-aminophenol. This study will help provide structural information of utmost importance in understanding de novo computational design variables impacting the functional activities of a protein.

Keywords: metalloproteins, protein design, de novo protein, biocatalysis

Procedia PDF Downloads 151

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 75

Authors: Dammar Bahadur Adhikari

Abstract:

Community forestry in Nepal has got disproportionately high level of support from government and other actors in forestry sector. Even though master plan for forestry sector (1989) has highlighted community and private forestry as one component, the government policies and other intervention deliberately left out private forestry in its structure and programs. The study aimed at providing the pathway for formulating appropriate policies to address need of different kind of forest management regimes in Rautahat district, Nepal. The key areas the research focused were assessment of current status of private forestry, community forest users' understanding on private forestry; criteria for choosing species of private forestry and factors affecting establishment of private forestry in the area. Qualitative and quantitative data were collected employing questionnaire survey, rapid forest assessment and key informant interview. The study found out that forest policies are imposed due to intense pressure of exogenous forces than due to endogenous demand. Most of the local people opine that their traditional knowledge and skills are not sufficient for private forestry and hence need training on the matter. Likewise, local use, market value and rotation dictate the choice of species for plantation in private forests. Currently district forest office is the only government institution working in the area of private forestry all other governmental and non-governmental organizations have condoned. private forestry. Similarly, only permanent settlers in the area are found to establish private forests other forest users such as migrants and forest encroachers follow opportunistic behavior to meet their forest product need from community and national forests. In this regard, the study recommends taking appropriate step to support other forest management system including private forestry provide community forestry the benefits of competition as suggested by Darwin in 18th century, one and half century back and to help alleviate poverty by channelizing benefits to household level.

Keywords: community forest, forest management, poverty, private forest, users’ group

Procedia PDF Downloads 341

Authors: Elena Maria Scalisi

Abstract:

The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

Procedia PDF Downloads 144

Authors: Sheng Yu Chen, Shi-Heng Wang

Abstract:

Aim: Based on human, animal experiments, and genetic studies, cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are inflammatory substances that are metabolized by 5-lipooxygenase from arachidonic acid, and these substances trigger asthma. In addition, the synthetic pathway of cysteinyl leukotriene is relevant to the increase in cardiovascular diseases such as myocardial ischemia and stroke. Given the situation, we aim to investigate whether cysteinyl leukotrienes receptor antagonist (LTRA), montelukast which cures those who have asthma has potential protective effects on cardiovascular diseases. Method: We conducted a cohort study, and enrolled participants which are newly diagnosed with asthma (ICD-9 CM code 493. X) between 2002 to 2011. The data source is from Taiwan National Health Insurance Research Database Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Among the remaining participants, every montelukast user was matched with two randomly non-users by sex, and age. The incident cardiovascular diseases, including myocardial infarction and ischemic stroke, were regarded as outcomes. We followed the participants until outcomes come first or the end of the following period. To explore the protective effect of montelukast on the risk of cardiovascular disease, we use multivariable Cox regression to estimate the hazard ratio with adjustment for potential confounding factors. Result: There are 55876 newly diagnosed asthma patients who had at least one claim of inpatient admission or at least three claims of outpatient records. We enrolled 5350 montelukast users and 10700 non-users in this cohort study. The following mean (±SD) time of the Montelukast group is 5 (±2.19 )years, and the non-users group is 6.2 5.47 (± 2.641) years. By using multivariable Cox regression, our analysis indicated that the risk of incident cardiovascular diseases between montelukast users (n=43, 0.8%) and non-users (n=111, 1.04%) is approximately equal. [adjusted hazard ratio 0.992; P-value:0.9643] Conclusion: In this population-based study, we found that the use of montelukast is not associated with a decrease in incident MI or IS.

Keywords: asthma, inflammation, montelukast, insurance research database, cardiovascular diseases

Procedia PDF Downloads 83

Authors: Nicholas Pearce, Eun-jin Kim

Abstract:

Pathologies of the cardiovascular (CV) system remain a serious and deadly health problem for human society. Computational modelling provides a relatively accessible tool for diagnosis, treatment, and research into CV disorders. However, numerical models of the CV system have largely focused on the function of the ventricles, frequently overlooking the behaviour of the atria. Furthermore, in the study of the pressure-volume relationship of the heart, which is a key diagnosis of cardiac vascular pathologies, previous works often evoke popular yet questionable time-varying elastance (TVE) method that imposes the pressure-volume relationship instead of calculating it consistently. Despite the convenience of the TVE method, there have been various indications of its limitations and the need for checking its validity in different scenarios. A model of the combined left ventricle (LV) and left atrium (LA) is presented, which consistently considers various feedback mechanisms in the heart without having to use the TVE method. Specifically, a synergistic model of the left ventricle is extended and modified to include the function of the LA. The synergy of the original model is preserved by modelling the electro-mechanical and chemical functions of the micro-scale myofiber for the LA and integrating it with the microscale and macro-organ-scale heart dynamics of the left ventricle and CV circulation. The atrioventricular node function is included and forms the conduction pathway for electrical signals between the atria and ventricle. The model reproduces the essential features of LA behaviour, such as the two-phase pressure-volume relationship and the classic figure of eight pressure-volume loops. Using this model, disorders in the internal cardiac electrical signalling are investigated by recreating the mechano-electric feedback (MEF), which is impossible where the time-varying elastance method is used. The effects of AV node block and slow conduction are then investigated in the presence of an atrial arrhythmia. It is found that electrical disorders and arrhythmia in the LA degrade the CV system by reducing the cardiac output, power, and heart rate.

Keywords: cardiovascular system, left atrium, numerical model, MEF

Procedia PDF Downloads 116

Authors: Roongtiwa Chobchuen, Angkana Srikhan, Pattra Wattanapan

Abstract:

Background: Neurogenic bowel is common condition after spinal cord injury. Most of spinal cord injured patients have motor weakness, mobility impairment which leads to constipation. Moreover, the neural pathway involving bowel function is interrupted. Therefore, the bowel management program should be implemented in nursing care in the earliest time after the onset of the disease to prevent the morbidity and mortality. Objective: To study the outcome of bowel management program of the patients with spinal cord injury who admitted for rehabilitation program. Study design: Descriptive study. Setting: Rehabilitation ward in Srinagarind Hospital. Populations: patients with subacute to chronic spinal cord injury who admitted at rehabilitation ward, Srinagarind hospital, aged over 18 years old. Instrument: The neurogenic bowel dysfunction score (NBDS) was used to determine the severity of neurogenic bowel. Procedure and statistical analysis: All participants were asked to complete the demographic data; age gender, duration of disease, diagnosis. The individual bowel function was assessed using NBDS at admission. The patients and caregivers were trained by nurses about the bowel management program which consisted of diet modification, abdominal massage, digital stimulation, stool evacuation including medication and physical activity. The outcome of the bowel management program was assessed by NBDS at discharge. The chi-square test was used to detect the difference in severity of neurogenic bowel at admission and discharge. Results: Sixteen spinal cord injured patients were enrolled in the study (age 45 ± 17 years old, 69% were male). Most of them (50%) were tetraplegia. On the admission, 12.5%, 12.5%, 43.75% and 31.25% were categorized as very minor (NBDS 0-6), minor (NBDS 7-9), moderate (NBDS 10-13) and severe (NBDS 14+) respectively. The severity of neurogenic bowel was decreased significantly at discharge (56.25%, 18.755%, 18.75% and 6.25% for very minor, minor, moderate and severe group respectively; p < 0.001) compared with NBDS at admission. Conclusions: Implementation of the effective bowel program decrease the severity of the neurogenic bowel in patient with spinal cord injury.

Keywords: neurogenic bowel, NBDS, spinal cord injury, bowel program

Procedia PDF Downloads 244

Authors: Fei Sun, Meilan Xu, Jianghui Zhu, Maria Stefanie Dwiyanti, Cheolwoo Park, Fanjiang Kong, Baohui Liu, Tetsuya Yamada, Jun Abe

Abstract:

Reduced or lack of sensitivity to long daylengths is a key character for soybean, a short-day crop, to adapt to higher latitudinal environments. However, the photoperiod-insensitivity often results in a reduction of the duration of vegetative growth and final yield. To overcome this limitation, a photoperiod insensitive line (RIL16) was developed in this study that delayed flowering from the recombinant inbred population derived from a cross between a photoperiod-insensitive cultivar AGS292 and a late-flowering Thai cultivar K3. Expression analyses under SD and LD conditions revealed that the expression levels of FLOWERING LOCUS T (FT) orthologues, FT2a and FT5a, were lowered in RIL16 relative to AGS292, although the expression of E1, a soybean-specific suppressor for FTs, was inhibited in both conditions. A soybean orthologue of TARGET OF EAT1 (TOE1), another suppressor of FT, showed an upregulated expression in RIL16, which appeared to reflect a lower expression of miR172a. Our data suggest that the delayed flowering of RIL16 most likely is controlled by genes involved in an age-dependent pathway in flowering. The QTL analysis based on 1,125 SNPs obtained from Restriction Site Associated DNA Sequencing revealed two major QTLs for flowering dates in Chromosome 16 and two minor QTLs in Chromosome 4, all of which accounted for 55% and 48% of the whole variations observed in natural day length and artificially-induced long day length conditions, respectively. The intervals of the major QTLs harbored FT2a and FT5a, respectively, on the basis of annotated genes in the Williams 82 reference genome. Sequencing analysis further revealed a nonsynonymous mutation in FT2a and an SNP in the 3′ UTR region of FT5a. A further study may elucidate a detailed mechanism underlying the QTL for late flowering. The alleles from K3 at the two QTLs can be used singly or in combination to retain an appropriate duration of vegetative growth to maximize the final yield of photoperiod-insensitive soybeans.

Keywords: FT genes, miR72a, photoperiod-insensitive, soybean flowering

Procedia PDF Downloads 221

Authors: Kishor Kumar Sadasivuni, Mizaj Shabil Sha, Assim Alajali, Godlaveeti Sreenivasa Kumar, Aboubakr M. Abdullah, Bijandra Kumar, Mithra Geetha

Abstract:

A potential pathway for efficient hydrogen production from water splitting electrolysis involves catalysis or electrocatalysis, which plays a crucial role in energy conversion and storage. Hydrogen generated by electrocatalytic water splitting requires active, stable, and low-cost catalysts or electrocatalysts to be developed for practical applications. In this study, we evaluated combination of 2D materials of NiS nanoparticle catalysts for hydrogen evolution reactions. The photocatalytic H₂ production rate of this nanoparticle is high and exceeds that obtained on components alone. Nanoparticles serve as electron collectors and transporters, which explains this improvement. Moreover, a current density was recorded at reduced working potential by 0.393 mA. Calculations based on density functional theory indicate that the nanoparticle's hydrogen evolution reaction catalytic activity is caused by strong interaction between its components at the interface. The samples were analyzed by XPS and morphologically by FESEM for the best outcome, depending on their structural shapes. Use XPS and morphologically by FESEM for the best results. This nanocomposite demonstrated higher electro-catalytic activity, and a low tafel slope of 60 mV/dec. Additionally, despite 1000 cycles into a durability test, the electrocatalyst still displays excellent stability with minimal current loss. The produced catalyst has shown considerable potential for use in the evolution of hydrogen due to its robust synthesis. According to these findings, the combination of 2D materials of nickel sulfide sample functions as good electocatalyst for H₂ evolution. Additionally, the research being done in this fascinating field will surely push nickel sulfide-based technology closer to becoming an industrial reality and revolutionize existing energy issues in a sustainable and clean manner.

Keywords: electrochemical hydrogenation, nickel sulfide, electrocatalysts, energy conversion, catalyst

Procedia PDF Downloads 126

Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming

Abstract:

Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.

Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry

Procedia PDF Downloads 295

Authors: Yong-Hui Zheng

Abstract:

Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

Procedia PDF Downloads 71

Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks

Abstract:

Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.

Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress

Procedia PDF Downloads 243

Authors: Anjali Roy, Mirza S. Baig

Abstract:

Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

Procedia PDF Downloads 127

Authors: Bharati Mehta, Manish Parakh, Bharti Bhandari, Sneha Ambwani

Abstract:

Speech and language delay (SLD) is seen commonly as a co-morbidity in children having severe resistant focal and generalized, syndromic and symptomatic epilepsies. It is however not clear whether epilepsy contributes to or is a mere association in the pathogenesis of SLD. Also, it is acknowledged that Auditory Brainstem Evoked Responses (ABER), besides used for evaluating hearing threshold, also aid in prognostication of neurological disorders and abnormalities in the hearing pathway in the brainstem. There is no circumscribed or surrogate neurophysiologic laboratory marker to adjudge the extent of SLD. The current study was designed to evaluate the abnormalities in Electroencephalography (EEG) and ABER in children with SLD who do not have an overt hearing deficit or autism. 94 children of age group 2-8 years with predominant SLD and without any gross motor developmental delay, head injury, gross hearing disorder, cleft lip/palate and autism were selected. Standard video Electroencephalography using the 10:20 international system and ABER after click stimulus with intensities 110 db until 40 db was performed in all children. EEG was abnormal in 47.9% (n= 45; 36 boys and 9 girls) children. In the children with abnormal EEG, 64.5% (n=29) had an abnormal background, 57.8% (n=27) had presence of generalized interictal epileptiform discharges (IEDs), 20% (n=9) had focal epileptiform discharges exclusively from left side and 33.3% (n=15) had multifocal IEDs occurring both in isolation or associated with generalised abnormalities. In ABER, surprisingly, the peak latencies for waves I, III & V, inter-peak latencies I-III & I-V, III-V and wave amplitude ratio V/I, were found within normal limits in both ears of all the children. Thus in the current study it is certain that presence of generalized IEDs in EEG are seen in higher frequency with SLD and focal IEDs are seen exclusively in left hemisphere in these children. It may be possible that even with generalized EEG abnormalities present in these children, left hemispheric abnormalities as a part of this generalized dysfunction may be responsible for the speech and language dysfunction. The current study also emphasizes that ABER may not be routinely recommended as diagnostic or prognostic tool in children with SLD without frank hearing deficit or autism, thus reducing the burden on electro physiologists, laboratories and saving time and financial resources.

Keywords: ABER, EEG, speech, language delay

Procedia PDF Downloads 536

Authors: Asif Zaman, Moinul Islam Zaber, Amin Ahsan Ali

Abstract:

In recent years of industrialization, the South Asian countries are being affected by air pollution due to a severe increase in fine particulate matter 2.5 (PM₂.₅). Among them, Bangladesh is one of the most polluting countries. In this paper, statistical analyses were conducted on the time series of PM₂.₅ from various districts in Bangladesh, mostly around Dhaka city. Research has been conducted on the dynamic interactions and relationships between PM₂.₅ concentrations in different zones. The study is conducted toward understanding the characteristics of PM₂.₅, such as spatial-temporal characterization, correlation of other contributors behind air pollution such as human activities, driving factors and environmental casualties. Clustering on the data gave an insight on the districts groups based on their AQI frequency as representative districts. Seasonality analysis on hourly and monthly frequency found higher concentration of fine particles in nighttime and winter season, respectively. Cross correlation analysis discovered a phenomenon of correlations among cities based on time-lagged series of air particle readings and visualization framework is developed for observing interaction in PM₂.₅ concentrations between cities. Significant time-lagged correlations were discovered between the PM₂.₅ time series in different city groups throughout the country by cross correlation analysis. Additionally, seasonal heatmaps depict that the pooled series correlations are less significant in warmer months, and among cities of greater geographic distance as well as time lag magnitude and direction of the best shifted correlated particulate matter time series among districts change seasonally. The geographic map visualization demonstrates spatial behaviour of air pollution among districts around Dhaka city and the significant effect of wind direction as the vital actor on correlated shifted time series. The visualization framework has multipurpose usage from gathering insight of general and seasonal air quality of Bangladesh to determining the pathway of regional transportation of air pollution.

Keywords: air quality, particles, cross correlation, seasonality

Procedia PDF Downloads 105

Authors: Ira Irawati, Muhammad Rangga Sururi

Abstract:

The expansion of built-up areas in many cities, particularly, as the consequences of urbanization process, is a common phenomenon in our contemporary world. As happened in many cities in developing world, this horizontal expansion let only a handful size of the area left for green open spaces, creating an extreme unbalance between built-up and green spaces. Combined with the high density and variety of human activities with its transportation modes; a process of urban heat island will occur, resulting in an increase in air temperature. This is one of the indicators of decreasing of the quality of urban microclimate. This paper will explore the effect of several variables of built-up areas and open spaces to the increase of air temperature using multiple linear regression analysis. We selected 11 zones within the radius of 1 km in Inner Bandung city center, and each zones measured within 300 m radius to represent the variety of land use, as well as the composition of buildings and green open spaces. By using a quantitative method which is multiple linear regression analysis, six dependent variables which are a) tree density-x1, b) shade level of tree-x2, c) surface area of buildings’ side which are facing west and east-x3, d) surface area of building side material-x4, e) surface area of pathway material, and f) numbers of motorized vehicles-x6; are calculated to find those influence to the air temperature as an independent variable-y. Finally, the relationship between those variables shows in this equation: y = 30.316 - 3.689 X1 – 6.563 X2 + 0.002 X3 – 2,517E6 X4 + 1.919E-9 X5 + 1.952E-4 X6. It shows that the existence of vegetation has a great impact on lowering temperature. In another way around, built up the area and motorized vehicles would increase the temperature. However, one component of built up area, the surface area of buildings’ sides which are facing west and east, has different result due to the building material is classified in low-middle heat capacity.

Keywords: built-up area, microclimate, vehicles, urban heat island, vegetation

Procedia PDF Downloads 259