Search results for: mitochondrial homeostasis

Authors: Yin Hua Zhang

Abstract:

Cardiac metabolism is essential in myocardial contraction. In addition to glucose, fatty acids (FA) are essential in producing energy in the myocardium since FA-dependent beta-oxidation accounts for > 70-90% of cellular ATP under resting conditions. However, metabolism shifts from FAs to glucose utilization during disease progression (e.g. hypertrophy and ischemic myocardium), where glucose oxidation and glycolysis become the predominant sources of cellular ATP. At advanced failing stage, both glycolysis and beta-oxidation are dysregulated, result in insufficient supply of intracellular ATP and weakened myocardial contractility. Undeniably, our understandings of myocyte function in healthy and diseased hearts are based on glucose (10 mM)-dependent metabolism because glucose is the “sole” metabolic substrate in most of the physiological experiments. In view of the importance of FAs in cardiovascular health and diseases, we aimed to elucidate the impacts of FA supplementation on myocyte contractility and evaluate cellular mechanisms those mediate the functions in normal heart and with pathological stress. In particular, we have investigated cardiac excitation-contraction (E-C) coupling in the presence and absence of FAs in normal and hypertensive rat left ventricular (LV) myocytes. Our results reveal that FAs increase mitochondrial activity, intracellular [Ca²+]i, and LV myocyte contraction in healthy LV myocytes, whereas FA-dependent cardiac inotropyis attenuated in hypertension. FA-dependent myofilament Ca²+ desensitization could be fundamental in regulating [Ca²+]i. Collectively, FAs supplementation resets cardiac E-C coupling scheme in healthy and diseased hearts.

Keywords: hypertension, fatty acid, heart, calcium

Procedia PDF Downloads 109

Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

Abstract:

The family of phosphodiesterases (PDEs) plays a critical role in control of the level, localization, and duration of intracellular 3’-5’-cyclic adenosine monophosphate (cAMP) and 3’-5’-cyclic guanosine monophosphate (cGMP) signals by specifically hydrolyzing these cyclic nucleotides. As the involvement of cyclic nucleotide second messengers in cell signaling and homeostasis is established, the regulation of these pathways in the brain by various PDE isoforms is an area of considerable interest, as they are involved in nearly all brain functions and in the etiology of neuropsychiatric diseases. The PDE10A isoform, isolated from different species and characterized regarding structure and function, has received much attention in recent years, particularly in the context of schizophrenia and Huntington’s disease, which are both related to a role of PDE10A in the regulation of striatal dopaminergic neurotransmission. Quinazoline analogue 1-(4-methoxyphenyl)-6,7-dimethoxyquinazoline, was evaluated as specific PET marker for phosphodiesterase (PDE) 10A. Here, we report the radiosynthesis of [11C]2 and the in vitro and in vivo evaluation of [11C]2 as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of [11C]2 was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]2 was obtained with ∼50% radiochemical yield. PET imaging studies in rat brain displayed initial specific uptake with very rapid clearance of [11C]2 from brain. Though [11C]2 is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Modified analogue of quinazoline having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Keywords: PDE10A, PET, radiotracer, quinazoline

Procedia PDF Downloads 186

Authors: Zain Ul Abdin, Mirza Aizaz Asim, Rao Sohail Ahmad Khan, Luqman Amrao, Fiaz Hussain, Hasooba Hira, Saqi Kosar Abbas

Abstract:

The success of Integrated vector management programmes mainly depends on the correct identification of insect vector species involved in vector borne diseases. Based on molecular data the most important insect species involved as vectors for Zoonotic diseases in Pakistan were identified. The precise and accurate identification of such type of organism is only possible through molecular based techniques like “DNA barcoding”. Morphological species identification in insects at any life stage, is very challenging, therefore, DNA barcoding was used as a tool for rapid and accurate species identification in a wide variety of taxa across the globe and parallel studies revealed that DNA barcoding data can be effectively used in resolving taxonomic ambiguities, detection of cryptic diversity, invasion biology, description of new species etc. A comprehensive survey was carried out for the collection of insects (both adult and immature stages) in district Faisalabad, Pakistan and their DNA was extracted and mitochondrial cytochrome oxidase subunit I (COI-59) barcode sequences was used for molecular identification of immature and adult life stage.This preliminary research work opens new frontiers for developing sustainable insect vectors management programmes for saving lives of mankind from fatal diseases.

Keywords: zoonotic diseases, cytochrome oxidase, and insect vectors, CO1

Procedia PDF Downloads 168

Authors: Luana N. Cardozo, Debora A. S. Coutinho, Fabiola Lagher, Bruno J. G. Silva, Ivonilce Venture, Mainara Tesser, Graciela Venera

Abstract:

Ostrich oil is used as food in Brazil, and it has been the subject of scientific research because it contains essential fatty acids (Omega 3, 6, 7, and 9), which provide benefits to human health. Alkylglycerols are lipid ethers consisted of a saturated or unsaturated hydrocarbon chain joined by ether-type bonding to one of the glycerol hydroxyls. It is known that supplementation with alkylglycerols can act significantly on the functioning of immune system cells, both in pathological situations and in homeostasis. Objective: Analyze the presence of alkylglycerols in ostrich oil. Methods: The ostrich oil was bought from an industry that manufactures the product for sale as food, located in Mirante da Serra, northern Brazil. The samples were sent for analysis to the chemistry department of the Federal University of Paraná, where they were analyzed by the gas chromatography method. Results: The analysis of the ostrich oil presented alkylglycerols in area 514505154. Comparison, it is possible to observe that shark liver oil contains the area 26190196, and the difference between both is highly significant. Conclusion: The importance of alkylglycerol supplementation for the immune system is known. The analysis of the results made it possible to verify the presence of alkylglycerols in the ostrich oil, which is five times higher than in the shark liver oil, that would be the largest source food, but was surpassed by the ostrich oil until the present time. The present study emphasizes that ostrich oil can be considered a food source of alkylglycerols and may play a promising role in the immune system because it contains such substance, but further studies are needed to prove its performance in the body.

Keywords: ostrich oil, nutritional composition, alkylglycerols, food

Procedia PDF Downloads 141

Authors: Valdrina Ajeti, Icko Gjorgoski

Abstract:

Stress can be a reason for some physiological and biological disorders in the body. The antioxidative defense system is necessary for the maintenance of redox homeostasis in organisms. Because of its antioxidant effect, alkaline water (AW) is the focus of scientific interest. Adding AW and co-treatment with sodium ascorbate (SA) is expected for the organism to act preventively to hyperthermic stress. To investigate the effect of AW and SA on glucose and cortisol levels during acute hyperthermic stress, white female Wistar laboratory rats, divided into three groups of 10 individuals, were exposed to heat for 80 min, for 21 days. Acute hyperthermic exposure at 41˚C was a cause for oxidative stress. The first group is the control group, the second group is treated with AW, and the third group with AW and SA. Plasma glucose levels were determined by colorimetric method and cortisol was measured using the enzyme-linked immunosorbent assay method. The comparison of the means was made using the Tukey test. Differences were considered significant at a level of p < 0.05. Our results show that levels of glucose and cortisol have been increased in the group treated with AW on the 21st day after treatment (p < 0.0001), but not on the 7th and 14th day as compared to the control group. Also, co-treatment of animals with AW and SA significantly increased the levels of glucose and cortisol on the 21st day after treatment showing a synergistic effect. The individual action of AW, as well as synergism with SA, caused a high protective effect on oxidative damage.

Keywords: alkaline water, sodium ascorbate, hyperthermic stress, glucose, cortisol

Procedia PDF Downloads 131

Authors: Lu Yang, Keng Po Lai

Abstract:

Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

Procedia PDF Downloads 122

Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

Abstract:

Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: TSPO, molecular modeling, imaging, docking

Procedia PDF Downloads 462

Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan

Abstract:

Gastric cancer (GC) has high morbidity and fatality rate in various countries and is still one of the most frequent and deadly diseases. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in the normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all types of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis and mutation screening by monetering RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of inactivation of gastrokines. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age or cancer type of patients. Reduced of gastrokine genes seems to occur at the initial steps of cancer development. In order to understand the investigation between gastric cancer and diagnostic biomarker; further analysis is necessary.

Keywords: gastric cancer, diagnostic biomarker, nucleotide sequencing, semi-quantitative RT-PCR

Procedia PDF Downloads 472

Authors: Chaomeng Liu, Li Li, Xiao Wang, Li Ren, Qinge Zhang

Abstract:

Late-life depression (LLD) is a prevalent mental disorder among the elderly, frequently accompanied by significant cognitive decline, and has emerged as a worldwide public health concern. Microglia, astrocytes, and peripheral immune cells play pivotal roles in regulating inflammatory responses within the central nervous system (CNS) across diverse cerebral disorders. This review commences with the clinical research findings and accentuates the recent advancements pertaining to microglia and astrocytes in the neuroinflammation process of LLD. The reciprocal communication network between the CNS and immune system is of paramount importance in the pathogenesis of depression and cognitive decline. Stress-induced downregulation of tight and gap junction proteins in the brain results in increased blood-brain barrier permeability and impaired astrocyte function. Concurrently, activated microglia release inflammatory mediators, initiating the kynurenine metabolic pathway and exacerbating the quinolinic acid/kynurenic acid imbalance. Moreover, the balance between Th17 and Treg cells is implicated in the preservation of immune homeostasis within the cerebral milieu of individuals suffering from LLD. The ultimate objective of this review is to present future strategies for the management and treatment of LLD, informed by the most recent advancements in research, with the aim of averting or postponing the onset of AD.

Keywords: neuroinflammation, late-life depression, microglia, astrocytes, central nervous system, blood-brain barrier, Kynurenine pathway

Procedia PDF Downloads 44

Authors: Michaela Dušková, Kateřina Šimůnková, Martin Hill, Hana Hruškovičová, Hana Pospíšilová, Eva Králíková, Luboslav Stárka

Abstract:

Smoking represents the most widespread substance dependence in the world. Several studies show the nicotine's ability to alter women hormonal homeostasis. Women smokers have higher testosterone and lower estradiol levels throughout life compared to non-smoker women. We monitored the effect of smoking discontinuation on steroid spectrum with 40 premenopausal and 60 postmenopausal women smokers. These women had been examined before they discontinued smoking and also after 6, 12, 24, and 48 weeks of abstinence. At each examination, blood was collected to determine steroid spectrum (measured by GC-MS), LH, FSH, and SHBG (measured by IRMA). Repeated measures ANOVA model was used for evaluation of the data. The study has been approved by the local Ethics Committee. Given the small number of premenopausal women who endured not to smoke, only the first 6 week period data could be analyzed. A slight increase in androgens after the smoking discontinuation occurred. In postmenopausal women, an increase in testosterone, dihydrotestosterone, dehydroepiandrosterone, and other androgens occurred, too. Nicotine replacement therapy, weight changes, and age does not play any role in the androgen level increase. The higher androgens levels correlated with failure in smoking cessation. Women smokers have higher androgen levels, which might play a role in smoking dependence development. Women successful in smoking cessation, compared to the non-successful ones, have lower androgen levels initially and also after smoking discontinuation. The question is what androgen levels women have before they start smoking.

Keywords: addiction, smoking, cessation, androgens

Procedia PDF Downloads 381

Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

Abstract:

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

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

Procedia PDF Downloads 143

Authors: Suwattana Visetnan, Premruethai Supungul, Sureerat Tang, Ikuo Hirono, Anchalee Tassanakajon, Vichien Rimphanitchayakit

Abstract:

In animals, infection by Gram-negative bacteria and certain viruses activates the Imd signaling pathway wherein the a NF-κB transcription factor, Relish, is a key regulatory protein for the synthesis of antimicrobial proteins. Infection by yellow head virus (YHV) activates the Imd pathway. To investigate the expression of genes involved in YHV infection and under the influence of PmRelish regulation, RNA interference and suppression subtractive hybridization (SSH) are employed. The genes in forward library expressed in shrimp after YHV infection and under the activity of PmRelish were obtained by subtracting the cDNAs from YHV-infected and PmRelish-knockdown shrimp with cDNAs from YHV-infected shrimp. Opposite subtraction gave a reverse library whereby an alternative set of genes under YHV infection and no PmRelish expression was obtained. Sequencing of 252 and 99 cDNA clones from the respective forward and reverse libraries were done and annotated through blast search against the GenBank sequences. Genes involved in defense and homeostasis were abundant in both libraries, 31% and 23% in the forward and reverse libraries, respectively. They were predominantly antimicrobial proteins, proteinases and proteinase inhibitors. The expression of antimicrobial protein genes, ALFPm3, crustinPm1, penaeidin3 and penaeidin5 were tested under PmRelish silencing and Gram-negative bacterium V. harveyi infection. Together with the results previously reported, the expression of penaeidin5 and also penaeidin3 but not ALFPm3 and crustinPm1 were under the regulation of PmRelish in the Imd pathway.

Keywords: relish, yellow head virus, penaeus monodon, antimicrobial proteins

Procedia PDF Downloads 212

Authors: Ankita Pathak, Ashok Munjal, Ravi Parkash

Abstract:

Plastic responses to multiple environmental stressors in wet or dry seasonal populations of tropical Drosophila species have received less attention. We tested plastic effects of heat hardening, acclimation to drought or starvation; and changes in trehalose, proline and body lipids in D. ananassae flies reared under wet or dry season specific conditions. Wet season flies revealed significant increase in heat knockdown, starvation resistance and body lipids after heat hardening. However, accumulation of proline was observed only after desiccation acclimation of dry season flies while wet season flies elicited no proline but trehalose only. Therefore, drought-induced proline can be a marker metabolite for dry season flies. Further, partial utilization of proline and trehalose under heat hardening reflects their possible thermoprotective effects. Heat hardening elicited cross-protection to starvation stress. Stressor-specific accumulation or utilization, as well as rates of metabolic change for each energy metabolite, were significantly higher in wet season flies than dry season flies. Energy metabolite changes due to inter-related stressors (heat vs. desiccation or starvation) resulted in possible maintenance of energetic homeostasis in wet or dry season flies. Thus, low or high humidity induced plastic changes in energy metabolites can provide cross-protection to seasonally varying climatic stressors.

Keywords: wet-dry seasons, plastic changes, stress related traits, energy metabolites, cross protection

Procedia PDF Downloads 170

Authors: Noura Shehab-Eldeen, Mohamed Elsherbeeny, Hossam Elmetwally, Mohamed Salama, Ahmed Lotfy, Mohamed Elgamal, Hussein Sheashaa, Mohamed Sobh

Abstract:

Mitochondrial toxins including papaverine may be implicated in the etiology and pathogenesis of Parkinson's disease. The aim was to detect the effect of papaverine on the proliferation and viability of neural stem cells. Rat neural progenitor cells were isolated from embryos (E14) brains. The dispersed tissues were allowed to settle, then, The supernatant was centrifuged at 1,000 g for 5 min. The pellet was placed in Hank’s solution cultured as free-floating neurospheres Dulbecco’s modified Eagle medium (DMEM) and Hams F12 (3:1) supplemented with B27 (Invitrogen GmBH, Karlsruhe, Germany), 20 ng/mL epidermal growth factor (EGF; Biosource, Karlsruhe, Germany), 20 ng/mL recombinant human fibroblast growth factor (rhFGF; R&D Systems, Wiesbaden-Nordenstadt, Germany), and penicillin and streptomycin (1:100; Invitrogen) at 37°C with 7.5% CO2 . Differentiation was initiated by growth factor withdrawal and plating onto a poly-d-lysine/ laminin matrix. The neurospheres were fed every 2-3 days by replacing 50% of the culture media with fresh media. The culture suspension was transferred to a dish containing 16 wells. The wells were divided as follows: 4 wells received no papaverine (control), 4 wells 1 u, 4 wells 5 u and 4 wells 10 u of papaverine solution. In the next 2 weeks, photography (0,4,5,11days) and viability test were done. The photographs were analysed. Results : papaverine didn't affect proliferation of neurospheres, while it affected viability compared to control , this was dose related. Conclusion: This indicates the harmful effect of papaverine suggesting it to be a candidate neurotoxin causing Parkinsonism.

Keywords: neurospheres, neural stem cells, papaverine, Parkinsonism

Procedia PDF Downloads 660

Authors: Richard L. Summers

Abstract:

The advanced computational analysis of biological systems is becoming increasingly dependent upon an understanding of the information-theoretic structure of the materials, energy and interactive processes that comprise those systems. The stability and survival of these living systems are fundamentally contingent upon their ability to acquire and process the meaning of information concerning the physical state of its biological continuum (biocontinuum). The drive for adaptive system reconciliation of a divergence from steady-state within this biocontinuum can be described by an information metric-based formulation of the process for actionable knowledge acquisition that incorporates the axiomatic inference of Kullback-Leibler information minimization driven by survival replicator dynamics. If the mathematical expression of this process is the Lagrangian integrand for any change within the biocontinuum then it can also be considered as an action functional for the living system. In the direct method of Lyapunov, such a summarizing mathematical formulation of global system behavior based on the driving forces of energy currents and constraints within the system can serve as a platform for the analysis of stability. As the system evolves in time in response to biocontinuum perturbations, the summarizing function then conveys information about its overall stability. This stability information portends survival and therefore has absolute existential meaning for the living system. The first derivative of the Lyapunov energy information function will have a negative trajectory toward a system's steady state if the driving force is dissipating. By contrast, system instability leading to system dissolution will have a positive trajectory. The direction and magnitude of the vector for the trajectory then serves as a quantifiable signature of the meaning associated with the living system’s stability information, homeostasis and survival potential.

Keywords: meaning, information, Lyapunov, living systems

Procedia PDF Downloads 131

Authors: Mohammed Althobiti, Patrick Booms, Dorota Fiszer, Philip Hopkins

Abstract:

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. MH results from anaesthetics induced breakdown of calcium homeostasis. RYR1 and CACN1AS mutations represent the aetiology in ~70% of the MH population. Previous studies indicate that up to 25% of MH patients carry no variants in these genes. Therefore, the aim of this study is to investigate the relationships between MH susceptibility and genes encoding skeletal muscle Ca2+ channels as well as accessory proteins. The JSRP, encoding JP-45, was previously sequenced and novel genetic variants were identified. The variant p.P108L (c.323C > T) was identified in exon 4 and encodes a change from a proline at amino acid 108 to leucine residue. The variant P108L was detected in two patients out of 50 with 4% frequency in the sample population. The alignment of DNA sequences in different species indicates highly conserved proline sequences involved in the substitution of the P108L variant. In this study, the variant P108L co-segregates with the SNP p.V92A (c.275T > C) at the same exon, both variants being inherited in the same two patients only. This indicates that the two variants may represent a haplotype. Therefore, a set of single nucleotide polymorphisms and statistical analysis will be used to investigate the effects of haplotypes on MH susceptibility. Furthermore, investigating the effect of the P108L variant in combination with RYR1 mutations or other genetic variants in other genes as a combination of two or more genetic variants, haplotypes may then provide stronger genetic evidence indicating that JSRP1 is associated with MH susceptibility. In conclusion, these preliminary results lend a potential modifier role of the variant P108L in JSRP1 in MH susceptibility and further investigations are suggested to confirm these results.

Keywords: JSRP1, malignant hyperthermia, RyR1, skeletal muscle

Procedia PDF Downloads 335

Authors: Claudius Peter Van Wyk

Abstract:

Given the increasingly manifest phenomena, as described in complexity theory, of volatility, uncertainty, complexity and ambiguity (VUCA), Taleb's notion of 'antifragility, has a significant contribution to make to positive psychology applied to wellbeing. Antifragility is argued to be fundamentally different from the concepts of resiliency; as the ability to recover from failure, and robustness; as the ability to resist failure. Rather it describes the capacity to reorganise in the face of stress in such a way as to cope more effectively with systemic challenges. The concept, which has been applied in disciplines ranging from physics, molecular biology, planning, engineering, and computer science, can now be considered for its application in individual human and social wellbeing. There are strong correlations to Antonovsky's model of 'salutogenesis' in which an attitude and competencies are developed of transforming burdening factors into greater resourcefulness. We demonstrate, from the perspective of neuroscience, how technology measuring nervous system coherence can be coupled to acquired psychodynamic approaches to not only identify contextual stressors, utilise biofeedback instruments for facilitating greater coherence, but apply these insights to specific life stressors that compromise well-being. Employing an on-going case study with BMW South Africa, the neurological mapping is demonstrated together with 'reframing' and emotional anchoring techniques from neurolinguistic programming. The argument is contextualised in the discipline of psychoneuroimmunology which describes the stress pathways from the CNS and endocrine systems and their impact on immune function and the capacity to restore homeostasis.

Keywords: antifragility, complexity, neuroscience, psychoneuroimmunology, salutogenesis, volatility

Procedia PDF Downloads 376

Authors: Masocorro Gawned, Stephen Myers, Guat Siew Chew

Abstract:

Nuclear Receptors (NR) are a super family of transcription factors that play a major role in lipid and glucose metabolism in skeletal muscle. Recently, pharmacological evidence supports the view that stimulation of nuclear receptors alleviates Type 2 Diabetes (T2D). The orphan nuclear receptors (ONR) are members of the nuclear receptor (NR) superfamily whose ligands and physiological functions remain unknown. To date, no systematic studies have been carried out to screen for ONRs expressed in insulin resistant (IR) skeletal muscle cells. Therefore, in this study, we have established a model for IR by treating C2C12 skeletal muscle cells with insulin (10nM) for 48 hours. Western Blot analysis of phosphorylated AKT confirmed IR. Real-time quantitative polymerase chain reaction (qPCR) results highlighted key ONRs including NUR77 (NR4A1), NURR1 (NR4A2) and NOR1 (NR4A3) which have been associated with fatty acid oxidation regulation and glucose homeostasis. Increased mRNA expression levels of estrogen-related receptors (ERRs), REV-ERBα, NUR77, NURR1, NOR1, in insulin resistant C2C12 skeletal muscle cells, indicated that these ONRs could potentially play a pivotal regulatory role of insulin secretion in lipid metabolism. Taken together, this study has successfully contributed to the complete analysis of ONR in IR, and has filled in an important void in the study and treatment of T2D.

Keywords: type 2 diabetes, orphan nuclear receptors, transcription receptors, quantitative mRNA expression

Procedia PDF Downloads 426

Authors: Supannika Klangphukhiew, Roongnapa Srichana, Rina Patramanon

Abstract:

Cortisol has been used as a well-known commercial stress biomarker. A homeostasis response to psychological stress is indicated by an increased level of cortisol produced in hypothalamus-pituitary-adrenal (HPA) axis. Chronic psychological stress contributing to the high level of cortisol relates to several health problems. In this study, the cortisol biosensor was fabricated that mimicked the natural receptors. The artificial antibodies were prepared using molecular imprinted polymer technique that can imitate the performance of natural anti-cortisol antibody with high stability. Cortisol-molecular imprinted polymer (cortisol-MIP) was obtained using the multi-step swelling and polymerization protocol with cortisol as a target molecule combining methacrylic acid:acrylamide (2:1) with bisacryloyl-1,2-dihydroxy-1,2-ethylenediamine and ethylenedioxy-N-methylamphetamine as cross-linkers. Cortisol-MIP was integrated to the sensor. It was coated on the disposable screen-printed carbon electrode (SPCE) for portable electrochemical analysis. The physical properties of Cortisol-MIP were characterized by means of electron microscope techniques. The binding characteristics were evaluated via covalent patterns changing in FTIR spectra which were related to voltammetry response. The performance of cortisol-MIP modified SPCE was investigated in terms of detection range, high selectivity with a detection limit of 1.28 ng/ml. The disposable cortisol biosensor represented an application of MIP technique to recognize steroids according to their structures with feasibility and cost-effectiveness that can be developed to use in point-of-care.

Keywords: stress biomarker, cortisol, molecular imprinted polymer, screen-printed carbon electrode

Procedia PDF Downloads 273

Authors: Bello Gonzalez, Setten Van M., Brouwer M.

Abstract:

The chicken small intestine represents a dynamic and complex organ in which the enzymatic digestion and absorption of nutrients take place. The development of an in vitro fermentation chicken small intestinal model could be used as an alternative to explore the interaction between the microbiota and nutrient metabolism and to enhance the efficacy of targeting interventions to improve animal health. In the present study we have developed an in vitro fermentation chicken ileum microbiota model for unrevealing the complex interaction of ileum microbial community under physiological conditions. A two-vessel continuous fermentation process simulating in real-time the physiological conditions of the ileum content (pH, temperature, microaerophilic/anoxic conditions, and peristaltic movements) has been standardized as a proof of concept. As inoculum, we use a pool of ileum microbial community obtained from chicken broilers at the age of day 14. The development and validation of the model provide insight into the initial characterization of the ileum microbial community and its dynamics over time-related to nutrient assimilation and fermentation. Samples can be collected at different time points and can be used to determine the microbial compositional structure, dynamics, and diversity over time. The results of studies using this in vitro model will serve as the foundation for the development of a whole small intestine in vitro fermentation chicken gastrointestinal model to complement our already established in vitro fermentation chicken caeca model. The insight gained from this model could provide us with some information about the nutritional strategies to restore and maintain chicken gut homeostasis. Moreover, the in vitro fermentation model will also allow us to study relationships between gut microbiota composition and its dynamics over time associated with nutrients, antimicrobial compounds, and disease modelling.

Keywords: broilers, in vitro model, ileum microbiota, fermentation

Procedia PDF Downloads 57

Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

Abstract:

The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

Procedia PDF Downloads 48

Authors: Oluwatosin Adetola Arojojoye, Olajumoke Olufunlayo Alao, Philip Odigili

Abstract:

This study investigated the extent of pollution in Eleyele River in Oyo State, Nigeria by investigating the antioxidant status and malondialdehyde levels (index of lipid peroxidation) in the organs of African Catfish, Clarias gariepinus from the river. Clarias gariepinus weighing between 250g-400g were collected from Eleyele River (a suspected polluted river) and Clarias gariepinus from a clean fish farm (Durantee fisheries) were used as the control. Levels of malondialdehyde, glutathione concentration (GSH) and activities of antioxidant enzymes - superoxide dismutase, catalase and glutathione-S-transferase (GST) were evaluated in the post-mitochondrial fractions of the liver, kidney and gills of the fishes. From the results, there were increases in malondialdehyde level and GSH concentration in the liver, kidney and gills of Clarias gariepinus from Eleyele River when compared with control. Glutathione-S-transferase activity was induced in the liver and kidney of Clarias gariepinus from Eleyele River when compared with control. However, the activity of this enzyme was depleted in the gills of fishes from Eleyele River compared with control. Also there was an induction in SOD activity in the liver of Clarias gariepinus from Eleyele River when compared with control but there was a decrease in the activity of this enzyme in the kidney and gills of fishes from Eleyele River compared with control. Increase in lipid peroxidation and alterations in antioxidant system in Clarias gariepinus from Eleyele River show that the fishes were under oxidative stress. These suggest that the river is polluted probably as a result of industrial, domestic and agricultural wastes frequently discharged into the river. This could pose serious health risks to consumers of water and aquatic organisms from the river.

Keywords: antioxidant, lipid peroxidation, Clarias gariepinus, Eleyele River

Procedia PDF Downloads 529

Authors: Taek Hwan Lee, Moon Ho Do, Lalita Subedi, Young Un Park, Sun Yeou Kim

Abstract:

Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: dolichos lablab, germination, neuroprotection, trigonelline

Procedia PDF Downloads 323

Authors: Stafford Stewart, Hui Yu, Rominder Suri

Abstract:

This paper publishes the results of the first known study conducted in urban Philadelphia waterways that simultaneously utilized anthropogenic chemical and biological markers to identify suitable indicators of untreated human waste and fecal pollution. A total of 13 outfall samples, 30 surface water samples, and 2 groundwater samples were analyzed for fecal contamination and untreated human waste using a suite of 25 chemical markers and 5 bio-markers. Pearson rank correlation tests were conducted to establish associations between the abundances of bio-markers and the concentrations of chemical markers. Results show that 16S rRNA gene of human-associated Bacteroidales (BacH) was very strongly correlated (0.76 – 0.97, p < 0.05) with labile chemical markers acetaminophen, cotinine, estriol, and urobilin. Likewise, human-specific F- RNA coliphages (F-RNA-II) and labile chemical markers, urobilin, ibuprofen, cotinine and estriol, were significantly correlated (0.77 – 0.95, p < 0.05). Similarly, a strong positive correlation (0.67 – 0.91, p < 0.05) was evident between the abundances of bio-markers BacH and F-RNA-II, and the concentrations of the conservative markers, trimethoprim, meprobamate, diltiazem, triclocarban, metformin, sucralose, gemfibrozil, sulfamethoxazole, and carbamazepine. Human mitochondrial DNA (MitoH) correlated moderately with labile markers nicotine and salicylic acid as well as with conservative markers metformin and triclocarban (0.31 – 0.47, p<0.05). This study showed that by associating chemical and biological markers, a robust technique was developed for fingerprinting source-specific untreated waste and fecal contamination in source waters.

Keywords: anthropogenic markers, bacteroidales, fecal pollution, source waters, wastewater

Procedia PDF Downloads 15

Authors: Samira Kilani-Morakchi, Amina Badi, Nadia Aribi

Abstract:

German cockroach, Blattella germanica, is known to be an important pest due to its high reproductive potential and its ability to build up large infectious populations. The infestations were generally controlled by neurotoxic insecticides including organophosphates (OP), carbamate and pyrethroids. An alternative cockroach’s control approach is the use insect growth regulators (IGRs). The relative fewer effects of these chemicals on non-target insects and animals, and their favourable environmental fate, make them attractive insecticides for inclusion in integrated pest management programmes. The juvenoids and chitin synthesis inhibitors are two classes of IGRs that have received the most attention for useful chemicals to manage German cockroaches while ecdysone agonists were mostly used to control Lepidopteran species. In the present study, the sublethal effects of the non-sreroidal ecdysone agonist tebufenozide were evaluated topically on adults of the B. germanica. The effects on reproduction were observed in adults females of cockroaches that survived exposure to LD25 (146 µg/g of insect) of tebufenozide. Dissection of treated females showed a clear reduction in both the number of oocytes per paired ovaries and the size of basal oocytes, as compared to controls. In addition, tebufenozide significantly reduced the mating success of pairs and altered the fertility as shown through the reduction of ootheca development and total absence of viable nymph. Tebufenozide disrupted the German cockroach reproduction by interfering with homeostasis of the insect hormones. In conclusion, the overall results suggested that tebufenozide can be used as a biorational insecticide for controlling cockroaches.

Keywords: B. germanica, ecdysteroid agonist, tebufenozide, reproduction

Procedia PDF Downloads 296

Authors: Cyoung-Huei Huang, Chiu-Li Yeh, Man-Hui Pai, Sung-Ling Yeh

Abstract:

This study evaluated the effect of different dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups in this study. Mice were fed for 24 d with an AIN-93G diet either with soybean oil (S), a mixture of soybean oil and low fish oil content (LF) or high fish oil content (HF). The ratio of n-6/n-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups provided 2% DSS in drinking water during day 15-19. All mice drank distilled water from day 20-24 for recovery and sacrificed on day 25. The results showed that colitis resulted in higher Th1, Th2, and Th17 and lower Treg percentages in the blood. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Further, the percentages of Th1, Th2, and Th17 cells in the blood were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with n-6/n-3 PUFA ratio 2:1 had more pronounce effects than ratio 4:1. These results suggest that diets with an n-6/n-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared to the n-6/n-3 PUFA ratio 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

Keywords: inflammatory bowel disease, n-3 polyunsaturated fatty acids, helper T lymphocyte, regulatory T lymphocyte

Procedia PDF Downloads 297

Authors: Sammy Kibor, Filip Huyghe, Marc Kochzius, James Kairo

Abstract:

Goldstripe Sardinella, Sardinella gibbosa, (Bleeker, 1849) is a commercially and ecologically important small pelagic fish common in the Western Indian Ocean region. The present study aimed to assess genetic diversity and population structure of the species in the Kenya-Tanzania transboundary area using mtDNA and msDNA markers. Some 630 bp sequence in the mitochondrial DNA (mtDNA) Cytochrome C Oxidase I (COI) and five polymorphic microsatellite DNA loci were analyzed. Fin clips of 309 individuals from eight locations within the transboundary area were collected between July and December 2018. The S. gibbosa individuals from the different locations were distinguishable from one another based on the mtDNA variation, as demonstrated with a neighbor-joining tree and minimum spanning network analysis. None of the identified 22 haplotypes were shared between Kenya and Tanzania. Gene diversity per locus was relatively high (0.271-0.751), highest Fis was 0.391. The structure analysis, discriminant analysis of Principal component (DAPC) and the pair-wise (FST = 0.136 P < 0.001) values after Bonferroni correction using five microsatellite loci provided clear inference on genetic differentiation and thus evidence of population structure of S. gibbosa along the Kenya-Tanzania coast. This study shows a high level of genetic diversity and the presence of population structure (Φst =0.078 P < 0.001) resulting to the existence of four populations giving a clear indication of minimum gene flow among the population. This information has application in the designing of marine protected areas, an important tool for marine conservation.

Keywords: marine connectivity, microsatellites, population genetics, transboundary

Procedia PDF Downloads 124

Authors: Allen Seylani

Abstract:

Lysosome-dependent autophagy is a nutrient-deprivation-induced evolutionarily conserved intracellular recycling program that sequestrates intracellular cargo into autophagosomes (AP), which then fuse with lysosomes to form autolysosomes (ALs) for cargo digestion. To restore free lysosomes, autophagic lysosome reformation (ALR) is initiated by extrusion of tubular structures from autolysosomes at the final stage of autophagy, in a process called lysosomal tubulation (LT). This project aimed to investigate the molecular mechanism of GCN5L1 in LT and the following lysosomal signaling. GCN5L1 belongs to the BORC multiprotein complexes and is involved in controlling lysosomal trafficking; however, the effect of GCN5L1 on lysosome tubulation remains largely unknown. Genetic ablation of GCN5L1 in the mouse primary hepatocytes showed dramatically increased autolysosomes (ALs), decreased lysosome regeneration and absence of lysosomal tubulation. This phenotype suggests the possibility of disruption in lysosome tubulation, which results in the disturbance of the overall lysosome homeostasis. The formation of tubulars from ALs requires kinesin motor protein KIF5B. Immunoprecipitation was employed and confirmed the interaction of GCN5L1 with the ARL8B-KIF5B complex, which recruited KIF5B to ALs. At the same time, GCN5L1 interacted with WHAMM, which promotes the actin nucleation factor, which brings actin cytoskeleton to ALs and initiates LT. Furthermore, impaired LT in GCN5L1 deficient hepatocytes was restored by overexpression of GCN5L1, and this rescue effect was attenuated by knockdown of KIF5B. Additionally, lysosomal mTORC1 activity was upregulated in GCN5L1-/- hepatocytes, while inhibition of mTORC1 abrogated the GCN5L1 mediated rescue of LT in knockout hepatocytes. Altogether these findings revealed a novel mechanism of ALR, in which a simultaneous interaction of GCN5L1 with KIF5B and WHAMM is required for LT and downstream mTORC1 signaling.

Keywords: autophagy, autolysosome, GCN5L1, lysosome

Procedia PDF Downloads 155

Authors: Adela Penesova, Zofia Radikova, Boris Bajer, Andrea Havranova, Miroslav Vlcek

Abstract:

Background: The aim of our study was to compare the effect of intensified lifestyle intervention on insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fibroblast growth factor (FGF) 21 after 8 weeks of lifestyle intervention. Methods: A group of 43 obese patients (13M/30F; 43.0±12.4 years; BMI (body mass index) 31.2±6.3 kg/m2 participated in a weight loss interventional program (NCT02325804) following an 8-week hypocaloric diet (-30% energy expenditure) and physical activity 150 minutes/week. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices according to Matsuda and Cederholm were calculated (ISImat and ISIced). Plasma ALT, AST, Fetuin-A, FGF 21, and physical fitness were measured. Results: The average reduction of body weight was 6.8±4.9 kg (0-15 kg; p=0.0006), accompanied with a significant reduction of body fat amount of fat mass (p=0.03), and waist circumference (p=0.02). Insulin sensitivity has been improved (IR HOMA 2.71±3.90 vs 1.24±0.83; p=0.01; ISIMat 6.64±4.38 vs 8.93±5.36 p ≤ 0.001). Total, LDL cholesterol, and triglycerides decreased (p=0.05, p=0.04, p=0.04, respectively). Physical fitness significantly improved after intervention (as measure VO2 max (maximal oxygen uptake) (p ≤ 0.001). ALT decreased significantly (0.44±0.26 vs post 0.33±0.18 ukat/l, p=0.004); however, AST not (pre 0.40±0.15 vs 0.35±0.09 ukat/l, p=0.07). Hepatokine Fetuin-A significantly decreased after intervention (43.1±10.8 vs 32.6±8.6 ng/ml, p < 0.001); however, FGF 21 levels tended to decrease (146±152 vs 132±164 pg/ml, p=0.07). Conclusion: 8-weeks of diet and physical activity intervention program in obese otherwise healthy subjects led to an improvement of insulin resistance parameters and liver marker profiles, as well as increased physical fitness. This study was supported by grants APVV 15-0228; VEGA 2/0161/16.

Keywords: obesity, diet, exercice, insulin sensitivity

Procedia PDF Downloads 201

Authors: Aly Kassem, Eman A. Sabet, Hanaa A. El-Hady, Doha S. Mohamed, Abeer Sheneef, Mona Fattouh, Mamdouh M. Esmat

Abstract:

Objective: Giardia lamblia parasite is the most common protozoal infection in human. Concomitant Helecobacter Pylori (H. pylori) and Giardia lamblia infection is common for their similar mode of transmission and strong correlation to socioeconomic levels. Only few reports had described gastric giardiasis. Our aim was to detect H. pylori and Giardia in gastric antral mucosal biopsies from patients with dyspepsia. The impact of both pathogens on clinical, endoscopic and histopathogical changes was studied. Methods: 48 patients with dyspepsia (group1) and 28 control patients (patients undergoing esophagogastroduodenoscopy EGD for reasons other than dyspepsia), (group 2) were studied. Endoscopic data were reported and gastric biopsy specimens were obtained for subsequent PCR assay for both organisms and for histopathological and electron microscopic examination. Results: Endoscopic antral gastritis and duodenal lesions were found in both groups, however, they were significantly more frequently in group 1 (p= 0.002 and P= 0.0005 respectively). Esophageal lesions, nodular antral gastritis, gastric ulcers and superficial corpal gastritis were found only in group 1. PCR detected H. pylori infection in 58% Vs 64 % for group 1 and group 2 respectively (P: NS). Giardia infection was present in 67 % Vs 42 % for group 1 and group 2 respectively (P=0.0003, Odd ratio=2.6). Co-infection with H. pylori and Giardia was present in 33% of group 1 Vs 36% for group 2 (P:NS). Abnormal histologic findings were found in both groups, however, intestinal metaplasia was found in group 1 only. Cellular abnormalities in the form of cytoplasmic vacuoles, mitochondrial destruction or nuclear abnormalities were found by Electron microscopic study in infected subjects of both groups. Conclusion: H. pylori is not the only gastric pathogen in our community, gastric giardiasis is another pathogen. Its contribution might be a factor in persistent dyspepsia after H. pylori eradication.

Keywords: dyspepsia, gastritis, Giardia lamblia, H. pylori

Procedia PDF Downloads 305