Search results for: metabolic pathway
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1383

Search results for: metabolic pathway

1323 Higher Consumption of White Rice Increase the Risk of Metabolic Syndrome in Adults with Abdominal Obesity

Authors: Zahra Bahadoran, Parvin Mirmiran, Fereidoun Azizi

Abstract:

Background: Higher consumption of white rice has been suggested as a risk factor for development of metabolic abnormalities. In this study we investigated the association between consumption of white rice and the 3-year occurrence of metabolic syndrome (MetS) in adults with and without abdominal obesity. Methods: This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study on 1476 adults, aged 19-70 years. Dietary intakes were measured, using a 168-food items validated semi-quantitative food frequency questionnaire at baseline. Biochemical and anthropometric measurements were evaluated at both baseline (2006-2008) and after 3-year follow-up (2009-2011). MetS and its components were defined according to the diagnostic criteria proposed by NCEP ATP III, and the new cutoff points of waist circumference for Iranian adults. Multiple logistic regression models were used to estimate the occurrence of the MetS in each quartile of white rice consumption. Results: The mean age of participants was 37.8±12.3 y, and mean BMI was 26.0±4.5 kg/m2 at baseline. The prevalence of MetS in subjects with abdominal obesity was significantly higher (40.9 vs. 16.2%, P<0.01). There was no significant difference in white rice consumption between the two groups. Mean daily intake of white rice was 93±59, 209±58, 262±60 and 432±224 g/d, in the first to fourth quartiles of white rice, respectively. Stratified analysis by categories of waist circumference showed that higher consumption of white rice was more strongly related to the risk of metabolic syndrome in participants who had abdominal obesity (OR: 2.34, 95% CI:1.14-4.41 vs. OR:0.99, 95% CI:0.60-1.65) Conclusion: We demonstrated that higher consumption of white rice may be a risk for development of metabolic syndrome in adults with abdominal obesity.

Keywords: white rice, abdominal obesity, metabolic syndrome, food science, triglycerides

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1322 Raman Spectroscopic of Cardioprotective Mechanism During the Metabolic Inhibition of Heart Cells

Authors: A. Almohammedi, A. J. Hudson, N. M. Storey

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Following ischaemia/reperfusion injury, as in a myocardial infraction, cardiac myocytes undergo oxidative stress which leads to several potential outcomes including; necrotic or apoptotic cell death or dysregulated calcium homeostasis or disruption of the electron transport chain. Several studies have shown that nitric oxide donors protect cardiomyocytes against ischemia and reperfusion. However until present, the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes is not fully understood and has not been investigated before using Raman spectroscopy. For these reasons, the aim of this study was to develop a novel technique, pre-resonance Raman spectroscopy, to investigate the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes exposed to metabolic inhibition and re-energisation. The results demonstrated the first time that Raman microspectroscopy technique has the capability to monitor the metabolic inhibition of cardiomyocytes and to monitor the effectiveness of cardioprotection by nitric oxide donor prior to metabolic inhibition of cardiomyocytes. Metabolic inhibition and reenergisation were used in this study to mimic the low and high oxygen levels experienced by cells during ischaemic and reperfusion treatments. A laser wavelength of 488 nm used in this study has been found to provide the most sensitive means of observe the cellular mechanisms of myoglobin during nitric oxide donor preconditioning, metabolic inhibition and re-energisation and did not cause any damage to the cells. The data also highlight the considerably different cellular responses to metabolic inhibition to ischaemia. Moreover, the data has been shown the relationship between the release of myoglobin and chemical ischemia where that the release of myoglobin from the cell only occurred if a cell did not recover contractility.

Keywords: ex vivo biospectroscopy, Raman spectroscopy, biophotonics, cardiomyocytes, ischaemia / reperfusion injury, cardioprotection, nitric oxide donor

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1321 Relationship Between Insulin Resistance and Some Coagulation and Fibrinolytic Parameters in Subjects With Metabolic Syndrome

Authors: Amany Ragab, Nashwa Khairat Abousamra, Omayma Saleh, Asmaa Higazy

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Insulin resistance syndrome has been shown to be associated with many coagulation and fibrinolytic proteins and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders. This study was conducted to determine the levels of some of the haemostatic parameters in subjects having metabolic syndrome and to correlate these values with the anthropometric and metabolic variables associated with this syndrome. The study included 46 obese non diabetic subjects of whom 28 subjects(group1) fulfilled the ATP III criteria of the metabolic syndrome and 18 subjects (group2) did not have metabolic syndrome as well as 14 lean subjects (group 3) of matched age and sex as a control group. Clinical and laboratory evaluation of the study groups stressed on anthropometric measurements (weight, height, body mass index, waist circumference, and sagittal abdominal diameter), blood pressure, and laboratory measurements of fasting plasma glucose, fasting insulin, serum lipids, tissue plasminogen activator (t-PA), antithrombin III activity (ATIII), protein C and von Willebrand factor (vWf) antigen. There was significant increase in the concentrations of t-PA and vWf antigens in subjects having metabolic syndrome (group 1) in comparison to the other groups while there were non-significant changes in the levels of protein C antigen and AT III activity. Both t-PA and vWf showed significant correlation with HOMA-IR as a measure of insulin sensitivity. The t-PA showed also significant correlation with most of the variables of metabolic syndrome including waist circumference, BMI, systolic blood pressure, fasting plasma glucose, fasting insulin, and HDL cholesterol. On the other hand, vWf showed significant correlations with fasting plasma glucose, fasting insulin and sagital abdominal diameter, with non-significant correlations with the other variables. Haemostatic and fibrinolytic parameters should be included in the features and characterization of the insulin resistance syndrome. t-PA and vWf antigens concentrations were increased in subjects with metabolic syndrome and correlated with the HOMA-IR measure of insulin sensitivity. Taking into consideration that both t-PA and vWf are mainly released from vascular endothelium, these findings could be an indicator of endothelial dysfunction in that group of subjects.

Keywords: insulin resistance, obesity, metabolic syndrome, coagulation

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1320 The Effect of Nepodin-Enrich Plant on Dyslipidemia and Hyperglycemia in High-Fat Diet-Induced Obese C57BL/6J Mice

Authors: Mi Kyeong Yu, Seon Jeong Lee, So Young Kim, Bora Choi, Young Mi Lee, Su-Jung Cho, Je Tae Woo, Myung-Sook Choi

Abstract:

A high-fat diet (HFD) induces excessive fat accumulation in white adipose tissue (WAT), which increases metabolic disorders such as obesity, dyslipidemia and type 2 diabetes. Many plants are known to have effects that improve metabolic disorders. Therefore, the aim of this present study is to investigate the effect of nepodin-enrich plant extract on dyslipidemia, hyperglycemia in high fat diet-induced C57BL/6J mice. Male C57BL/6J mice were randomly divided into two groups, and fed HFD (20% fat, w/w) or HFD supplemented with nepodin-enrich plant extract (NPE 0.005%, w/w) for 16 weeks. Body weight and food intake were measured every week. And we also analysed metabolic rates (respiratory quotient), blood glucose level, and plasma high-density lipoprotein (HDL)-cholesterol, free fatty acid, apolipoprotein (apo) A-1 and apo B levels. Food intakes and body weights were not different between NPE group and HFD group, while plasma apo B, free fatty acid levels, and blood glucose concentration were significantly decreased in NPE group than in HFD group. Furthermore, plasma apo A and HDL-cholesterol levels in NPE group were remarkably increased than in HFD group. Metabolic rates (respiratory quotient) were significantly increased in NPE group than in HFD group. These results indicate that NPE can alleviate dyslipidemia, hyperglycemia. Further studies are required to identify the effects of NPE on metabolic disorders.

Keywords: dyslipidemia, hyperglycemia, metabolic disorders, nepodin enrich plant extract

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1319 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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1318 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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1317 Tracking and Classifying Client Interactions with Personal Coaches

Authors: Kartik Thakore, Anna-Roza Tamas, Adam Cole

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The world health organization (WHO) reports that by 2030 more than 23.7 million deaths annually will be caused by Cardiovascular Diseases (CVDs); with a 2008 economic impact of $3.76 T. Metabolic syndrome is a disorder of multiple metabolic risk factors strongly indicated in the development of cardiovascular diseases. Guided lifestyle intervention driven by live coaching has been shown to have a positive impact on metabolic risk factors. Individuals’ path to improved (decreased) metabolic risk factors are driven by personal motivation and personalized messages delivered by coaches and augmented by technology. Using interactions captured between 400 individuals and 3 coaches over a program period of 500 days, a preliminary model was designed. A novel real time event tracking system was created to track and classify clients based on their genetic profile, baseline questionnaires and usage of a mobile application with live coaching sessions. Classification of clients and coaches was done using a support vector machines application build on Apache Spark, Stanford Natural Language Processing Library (SNLPL) and decision-modeling.

Keywords: guided lifestyle intervention, metabolic risk factors, personal coaching, support vector machines application, Apache Spark, natural language processing

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1316 Modified Genome-Scale Metabolic Model of Escherichia coli by Adding Hyaluronic Acid Biosynthesis-Related Enzymes (GLMU2 and HYAD) from Pasteurella multocida

Authors: P. Pasomboon, P. Chumnanpuen, T. E-kobon

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Hyaluronic acid (HA) consists of linear heteropolysaccharides repeat of D-glucuronic acid and N-acetyl-D-glucosamine. HA has various useful properties to maintain skin elasticity and moisture, reduce inflammation, and lubricate the movement of various body parts without causing immunogenic allergy. HA can be found in several animal tissues as well as in the capsule component of some bacteria including Pasteurella multocida. This study aimed to modify a genome-scale metabolic model of Escherichia coli using computational simulation and flux analysis methods to predict HA productivity under different carbon sources and nitrogen supplement by the addition of two enzymes (GLMU2 and HYAD) from P. multocida to improve the HA production under the specified amount of carbon sources and nitrogen supplements. Result revealed that threonine and aspartate supplement raised the HA production by 12.186%. Our analyses proposed the genome-scale metabolic model is useful for improving the HA production and narrows the number of conditions to be tested further.

Keywords: Pasteurella multocida, Escherichia coli, hyaluronic acid, genome-scale metabolic model, bioinformatics

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1315 Associations between Metabolic Syndrome and Bone Mineral Density and Trabecular Bone Score in Postmenopausal Women with Non-Vertebral Fractures

Authors: Vladyslav Povoroznyuk, Larysa Martynyuk, Iryna Syzonenko, Liliya Martynyuk

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Medical, social, and economic relevance of osteoporosis is caused by reducing quality of life, increasing disability and mortality of the patients as a result of fractures due to the low-energy trauma. This study is aimed to examine the associations of metabolic syndrome components, bone mineral density (BMD) and trabecular bone score (TBS) in menopausal women with non-vertebral fractures. 1161 menopausal women aged 50-79 year-old were examined and divided into three groups: A included 419 women with increased body weight (BMI - 25.0-29.9 kg/m2), B – 442 females with obesity (BMI >29.9 kg/m2)i and C – 300 women with metabolic syndrome (diagnosis according to IDF criteria, 2005). BMD of lumbar spine (L1-L4), femoral neck, total body and forearm was investigated with usage of dual-energy X-ray absorptiometry. The bone quality indexes were measured according to Med-Imaps installation. All analyses were performed using Statistical Package 6.0. BMD of lumbar spine (L1-L4), femoral neck, total body, and ultradistal radius was significant higher in women with obesity and metabolic syndrome compared to the pre-obese ones (p<0.001). TBS was significantly higher in women with increased body weight compared to obese and metabolic syndrome patients. Analysis showed significant positive correlation between waist circumference, triglycerides level and BMD of lumbar spine and femur. Significant negative association between serum HDL level and BMD of investigated sites was established. The TBS (L1-L4) indexes positively correlated with HDL (high-density lipoprotein) level. Despite the fact that BMD indexes were better in women with metabolic syndrome, the frequency of non-vertebral fractures was significantly higher in this group of patients.

Keywords: bone mineral density, trabecular bone score, metabolic syndrome, fracture

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1314 Alleviation of Endoplasmic Reticulum Stress in Mosquito Cells to Survive Dengue 2 Virus Infection

Authors: Jiun-Nan Hou, Tien-Huang Chen, Wei-June Chen

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Dengue viruses (DENVs) are naturally transmitted between humans by mosquito vectors. Mosquito cells usually survive DENV infection, allowing infected mosquitoes to retain an active status for virus transmission. In this study, we found that DENV2 virus infection in mosquito cells causes the unfolded protein response (UPR) that activates the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway, leading to shutdown of global protein translation in infected cells which was apparently regulated by the PERK signal pathway. According to observation in this study, the PERK signal pathway in DENV2-infected C6/36 cells alleviates ER stress, and reduces initiator and effector caspases, as well as the apoptosis rate via shutdown of cellular proteins. In fact, phosphorylation of eukaryotic initiation factor 2ɑ (eIF2ɑ) by the PERK signal pathway may impair recruitment of ribosomes that bind to the mRNA 5’-cap structure, resulting in an inhibitory effect on canonical cap-dependent cellular protein translation. The resultant pro-survival “byproduct” of infected mosquito cells is undoubtedly advantageous for viral replication. This finding provides insights into elucidating the PERK-mediated modulating web that is actively involved in dynamic protein synthesis, cell survival, and viral replication in mosquito cells.

Keywords: cap-dependent protein translation, dengue virus, endoplasmic reticulum stress, mosquito cells, PERK signal pathway

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1313 The Incidence of Metabolic Syndrome in Women with Impaired Reproductive Function According to Astana, Kazakhstan

Authors: A. T. Nakysh, A. S. Idrisov, S. A. Baidurin

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This work presents the results of a study the incidence of metabolic syndrome (MetS) in women with impaired reproductive function (IRF) according to the data of Astana, Kazakhstan. The anthropometric, biochemical and instrumental studies were conducted among 515 women, of which 53 patients with MetS according to IDF criteria, 2006, were selected. The frequency of occurrence of the IRF, due to MetS – 10.3% of cases according to the data of Astana. In women of childbearing age with IRF and the MetS, blood pressure (BP), indicators of carbohydrate and lipid metabolism were significantly higher and the level of high density lipoprotein (HDL) significantly lower compared to the same in women with the IRF without MetS. The hyperandrogenism, the hyperestrogenemia, the hyperprolactinemia and the hypoprogesteronemia were found in the patients with MetS and IRF, indicating the impact of MetS on the development of the polycystic ovary syndrome in 28% of cases and hyperplastic processes of the myometrium in 20% of cases.

Keywords: dyslipidemia, insulin resistance, metabolic syndrome, reproductive disorders, obesity

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1312 Effect of Inulin-Substituted Ice Cream on Waist Circumference and Blood Pressure of Adolescents with Abdominal Obesity

Authors: Nur H. Ahmad, Silvia S. Inge, Vanessa A. Julliete, A. Veraditias, Laila F. Febinda

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Abdominal obesity is a risk factor for metabolic syndrome and mostly found in adolescents. Waist circumference is related to abdominal obesity which has a significant effect on the increase of blood pressure. Inulin is one of prebiotic, that has health benefits by offering the potential for lipid management, that can be useful to decrease the risk factor of metabolic syndrome. The aim of the research is to evaluate the effect of 10 gram inulin-substituted ice cream in waist circumference and blood pressure of abdominal obesity adolescents. Inulin had the ability to produce Short Chain Fatty Acid which can improve blood pressure and waist circumference. Systolic blood pressure was significantly decreased in the treatment group (p=0.028) with the mean of reduction 7.35 ± 11.59 mmHg. However, diastolic blood pressure and waist circumference showed no significant effect. Waist circumference, systolic blood pressure and diastolic blood pressure was decreased in control group. These results suggest that inulin-substituted ice cream used as therapeutics and prevention for the early onset of metabolic syndrome.

Keywords: blood pressure, inulin, metabolic syndrome, waist circumference

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1311 Phytochemical and Biological Study of Chrozophora oblongifolia

Authors: Al-Braa Kashegari, Ali M. El-Halawany, Akram A. Shalabi, Sabrin R. M. Ibrahim, Hossam M. Abdallah

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Chemical investigation of Chrozophora oblongifolia resulted in the isolation of five major compounds that were identified as apeginin-7-O-glucoside (1), quercetin-3-O-glucuronic acid (2), quercetin-3-O-glacturonic acid (3), rutin (4), and 1,3,6-trigalloyl glucose (5). The identity of isolated compounds was assessed by different spectroscopic methods, including one- and two-dimensional NMR. The isolated compounds were tested for their antioxidant activity using different assays viz., DPPH, FRAP, ABTS, ORAC, and metal chelation effects. In addition, the inhibition of target enzymes involved in the metabolic syndrome, such as alpha-glucosidase and pancreatic lipase, were carried out. Moreover, the effect of the compounds on the advanced glycation end-products (AGEs) as one of the major complications of oxidative stress and hyperglycemia in metabolic syndromes were carried out using BSA‐fructose (bovine serum albumin), BSA-methylglyoxal, and arginine methylglyoxal models. The pure isolates showed a protective effect in metabolic syndromes as well as promising antioxidant activity. The results showed potent activity of compound 5 in all measured parameters meanwhile, none of the tested compounds showed activity against pancreatic lipase.

Keywords: Chrozophora oblongifolia, antioxidant, pancreatic lipase, metabolic syndromes

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1310 Metabolically Healthy Obesity and Protective Factors of Cardiovascular Diseases as a Result from a Longitudinal Study in Tebessa (East of Algeria)

Authors: Salima Taleb, Kafila Boulaba, Ahlem Yousfi, Nada Taleb, Difallah Basma

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Introduction: Obesity is recognized as a cardiovascular risk factor. It is associated with cardio-metabolic diseases. Its prevalence is increasing significantly in both rich and poor countries. However, there are obese people who have no metabolic disturbance. So we think obesity is not always a risk factor for an abnormal metabolic profile that increases the risk of cardiometabolic problems. However, there is no definition that allows us to identify the individual group Metabolically Healthy but Obese (MHO). Objective: The objective of this study is to evaluate the relationship between MHO and some factors associated with it. Methods: A longitudinal study is a prospective cohort study of 600 participants aged ≥18 years. Metabolic status was assessed by the following parameters: blood pressure, fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Body Mass Index (BMI) was calculated as weight (in kg) divided by height (m2), BMI = Weight/(Height)². According to the BMI value, our population was divided into four groups: underweight subjects with BMI <18.5 kg/m2, normal weight subjects with BMI = 18.5–24.9 kg/m², overweight subjects with BMI=25–29.9 kg/m², and obese subjects who have (BMI ≥ 30 kg/m²). A value of P < 0.05 was considered significant. Statistical processing was done using the SPSS 25 software. Results: During this study, 194 (32.33%) were identified as MHO among 416 (37%) obese individuals. The prevalence of the metabolically unhealthy phenotype among normal-weight individuals was (13.83%) vs. (37%) in obese individuals. Compared with metabolically healthy normal-weight individuals (10.93%), the prevalence of diabetes was (30.60%) in MHO, (20.59%) in metabolically unhealthy normal weight, and (52.29%) for metabolically unhealthy obese (p = 0.032). Blood pressure was significantly higher in MHO individuals than in metabolically healthy normal-weight individuals and in metabolically unhealthy obese than in metabolically unhealthy normal weight (P < 0.0001). Familial coronary artery disease does not appear to have an effect on the metabolic status of obese and normal-weight patients (P = 0.544). However, waist circumference appears to have an effect on the metabolic status of individuals (P < 0.0001). Conclusion: This study showed a high prevalence of metabolic profile disruption in normal-weight subjects and a high rate of overweight and/or obese people who are metabolically healthy. To understand the physiological mechanism related to these metabolic statuses, a thorough study is needed.

Keywords: metabolically health, obesity, factors associated, cardiovascular diseases

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1309 Neuro-Preservation Potential of Resveratrol Against High Fat High Fructose-Induced Metabolic Syndrome

Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

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The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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1308 Gene Names Identity Recognition Using Siamese Network for Biomedical Publications

Authors: Micheal Olaolu Arowolo, Muhammad Azam, Fei He, Mihail Popescu, Dong Xu

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As the quantity of biological articles rises, so does the number of biological route figures. Each route figure shows gene names and relationships. Annotating pathway diagrams manually is time-consuming. Advanced image understanding models could speed up curation, but they must be more precise. There is rich information in biological pathway figures. The first step to performing image understanding of these figures is to recognize gene names automatically. Classical optical character recognition methods have been employed for gene name recognition, but they are not optimized for literature mining data. This study devised a method to recognize an image bounding box of gene name as a photo using deep Siamese neural network models to outperform the existing methods using ResNet, DenseNet and Inception architectures, the results obtained about 84% accuracy.

Keywords: biological pathway, gene identification, object detection, Siamese network

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1307 Assessment of Obesity Parameters in Terms of Metabolic Age above and below Chronological Age in Adults

Authors: Orkide Donma, Mustafa M. Donma

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Chronologic age (CA) of individuals is closely related to obesity and generally affects the magnitude of obesity parameters. On the other hand, close association between basal metabolic rate (BMR) and metabolic age (MA) is also a matter of concern. It is suggested that MA higher than CA is the indicator of the need to improve the metabolic rate. In this study, the aim was to assess some commonly used obesity parameters, such as obesity degree, visceral adiposity, BMR, BMR-to-weight ratio, in several groups with varying differences between MA and CA values. The study comprises adults, whose ages vary between 18 and 79 years. Four groups were constituted. Group 1, 2, 3 and 4 were composed of 55, 33, 76 and 47 adults, respectively. The individuals exhibiting -1, 0 and +1 for their MA-CA values were involved in Group 1, which was considered as the control group. Those, whose MA-CA values varying between -5 and -10 participated in Group 2. Those, whose MAs above their real ages were divided into two groups [Group 3 (MA-CA; from +5 to + 10) and Group 4 (MA-CA; from +11 to + 12)]. Body mass index (BMI) values were calculated. TANITA body composition monitor using bioelectrical impedance analysis technology was used to obtain values for obesity degree, visceral adiposity, BMR and BMR-to-weight ratio. The compiled data were evaluated statistically using a statistical package program; SPSS. Mean ± SD values were determined. Correlation analyses were performed. The statistical significance degree was accepted as p < 0.05. The increase in BMR was positively correlated with obesity degree. MAs and CAs of the groups were 39.9 ± 16.8 vs 39.9 ± 16.7 years for Group 1, 45.0 ± 15.3 vs 51.4 ± 15.7 years for Group 2, 47.2 ± 12.7 vs 40.0 ± 12.7 years for Group 3, and 53.6 ± 14.8 vs 42 ± 14.8 years for Group 4. BMI values of the groups were 24.3 ± 3.6 kg/m2, 23.2 ± 1.7 kg/m2, 30.3 ± 3.8 kg/m2, and 40.1 ± 5.1 kg/m2 for Group 1, 2, 3 and 4, respectively. Values obtained for BMR were 1599 ± 328 kcal in Group 1, 1463 ± 198 kcal in Group 2, 1652 ± 350 kcal in Group 3, and 1890 ± 360 kcal in Group 4. A correlation was observed between BMR and MA-CA values in Group 1. No correlation was detected in other groups. On the other hand, statistically significant correlations between MA-CA values and obesity degree, BMI as well as BMR/weight were found in Group 3 and in Group 4. It was concluded that upon consideration of these findings in terms of MA-CA values, BMR-to-weight ratio was found to be much more useful indicator of the severe increase in obesity development than BMR. Also, the lack of associations between MA and BMR as well as BMR-to-weight ratio emphasize the importance of consideration of MA-CA values rather than MA.

Keywords: basal metabolic rate, basal metabolic rate-to-weight-ratio, chronologic age, metabolic age, obesity degree

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1306 Analysis of Taxonomic Compositions, Metabolic Pathways and Antibiotic Resistance Genes in Fish Gut Microbiome by Shotgun Metagenomics

Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

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1305 Acute Respiratory Distress Syndrome (ARDS) Developed Clinical Pathway: Suggested Protocol

Authors: Maha Salah, Hanaa Hashem, Mahmoud M. Alsagheir, Mohammed Salah

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Acute respiratory distress syndrome (ARDS) represents a complex clinical syndrome and carries a high risk for mortality. The severity of the clinical course, the uncertainty of the outcome, and the reliance on the full spectrum of critical care resources for treatment mean that the entire health care team is challenged. Researchers and clinicians have investigated the nature of the pathological process and explored treatment options with the goal of improving outcome. Through this application of research to practice, we know that some previous strategies have been ineffective, and innovations in mechanical ventilation, sedation, nutrition, and pharmacological intervention remain important research initiatives. Developed Clinical pathway is multidisciplinary plans of best clinical practice for this specified groups of patients that aid in the coordination and delivery of high quality care. They are a documented sequence of clinical interventions that help a patient to move, progressively through a clinical experience to a desired outcome. Although there is a lot of heterogeneity in patients with ARDS, this suggested developed clinical pathway with alternatives was built depended on a lot of researches and evidence based medicine and nursing practices which may be helping these patients to improve outcomes, quality of life and decrease mortality.

Keywords: acute respiratory distress syndrome (ARDS), clinical pathway, clinical syndrome

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1304 Is Presence of Psychotic Features Themselves Carry a Risk for Metabolic Syndrome?

Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

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Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

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1303 Combining Transcriptomics, Bioinformatics, Biosynthesis Networks and Chromatographic Analyses for Cotton Gossypium hirsutum L. Defense Volatiles Study

Authors: Ronald Villamar-Torres, Michael Staudt, Christopher Viot

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Cotton Gossypium hirsutum L. is one of the most important industrial crops, producing the world leading natural textile fiber, but is very prone to arthropod attacks that reduce crop yield and quality. Cotton cultivation, therefore, makes an outstanding use of chemical pesticides. In reaction to herbivorous arthropods, cotton plants nevertheless show natural defense reactions, in particular through volatile organic compounds (VOCs) emissions. These natural defense mechanisms are nowadays underutilized but have a very high potential for cotton cultivation, and elucidating their genetic bases will help to improve their use. Simulating herbivory attacks by mechanical wounding of cotton plants in greenhouse, we studied by qPCR the changes in gene expression for genes of the terpenoids biosynthesis pathway. Differentially expressed genes corresponded to higher levels of the terpenoids biosynthesis pathway and not to enzymes synthesizing particular terpenoids. The genes were mapped on the G. hirsutum L. reference genome; their global relationships inside the general metabolic pathways and the biosynthesis of secondary metabolites were visualized with iPath2. The chromatographic profiles of VOCs emissions indicated first monoterpenes and sesquiterpenes emissions, dominantly four molecules known to be involved in plant reactions to arthropod attacks. As a result, the study permitted to identify potential key genes for the emission of volatile terpenoids by cotton plants in reaction to an arthropod attack, opening possibilities for molecular-assisted cotton breeding in benefit of smallholder cotton growers.

Keywords: biosynthesis pathways, cotton, mechanisms of plant defense, terpenoids, volatile organic compounds

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1302 Eugenol Effects on Metabolic Syndrome Induced Liver Damages

Authors: Fatemeh Kourkinejad Gharaei, Tahereh Safari, Zahra Saebinasab

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Metabolic syndrome (MetS) is a set of risk factors associated with cardiovascular diseases, atherosclerosis, and type 2 diabetes. Nonalcoholic fatty liver disease (NAFLD) is the most important liver disorder in metabolic syndrome. High fructose consumption increases the risk of NAFLD. Eugenol shows anti-thrombotic, insulin-sensitive, fat-reducing effects. This study was designed to investigate the protective role of eugenol in NAFLD caused by metabolic syndrome. Methods: Thirty male Wistar rats were randomly divided into five groups; group 1, drinking water intake animals; group 2, fructose, group 3, fructose+eugenol solvent; group 4, fructose+ eugenol 50mg/kg and group 5, fructose+ eugenol 100mg/kg. At the end of the experiment, after 12 hours of fasting and under anesthesia, blood samples were taken for measurement of fast blood glucose (FBS), SGOT, AGPT, LDL, HDL, cholesterol, triglyceride. Results: FBG significantly increased in group 2 compared to group 1 (p < 0.001); however, it significantly decreased in groups 4 and 5 compared to group 2 (p < 0.05). SGOT and SGPT levels significantly increased in group 2 compared to drinking water alone (p < 0.001). However, SGOT and SGPT levels significantly decreased in groups 4 and 5. MDA and LTDS significantly increased in group 2 compared with drinking water alone (p < 0.01), while MDA and LTDS decreased in 4 and 5 groups compared to group 2 (p < 0.05), which confirms the pathology results related to the liver damage. Conclusion: Eugenol has protective effects on the liver and fat accumulation in liver cells.

Keywords: eugenol, fructose, metabolic syndrome, nonalcoholic fatty liver disease

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1301 PhenoScreen: Development of a Systems Biology Tool for Decision Making in Recurrent Urinary Tract Infections

Authors: Jonathan Josephs-Spaulding, Hannah Rettig, Simon Graspeunter, Jan Rupp, Christoph Kaleta

Abstract:

Background: Recurrent urinary tract infections (rUTIs) are a global cause of emergency room visits and represent a significant burden for public health systems. Therefore, metatranscriptomic approaches to investigate metabolic exchange and crosstalk between uropathogenic Escherichia coli (UPEC), which is responsible for 90% of UTIs, and collaborating pathogens of the urogenital microbiome is necessary to better understand the pathogenetic processes underlying rUTIs. Objectives: This study aims to determine the level in which uropathogens optimize the host urinary metabolic environment to succeed during invasion. By developing patient-specific metabolic models of infection, these observations can be taken advantage of for the precision treatment of human disease. Methods: To date, we have set up an rUTI patient cohort and observed various urine-associated pathogens. From this cohort, we developed patient-specific metabolic models to predict bladder microbiome metabolism during rUTIs. This was done by creating an in silico metabolomic urine environment, which is representative of human urine. Metabolic models of uptake and cross-feeding of rUTI pathogens were created from genomes in relation to the artificial urine environment. Finally, microbial interactions were constrained by metatranscriptomics to indicate patient-specific metabolic requirements of pathogenic communities. Results: Metabolite uptake and cross-feeding are essential for strain growth; therefore, we plan to design patient-specific treatments by adjusting urinary metabolites through nutritional regimens to counteract uropathogens by depleting essential growth metabolites. These methods will provide mechanistic insights into the metabolic components of rUTI pathogenesis to provide an evidence-based tool for infection treatment.

Keywords: recurrent urinary tract infections, human microbiome, uropathogenic Escherichia coli, UPEC, microbial ecology

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1300 Neuroprotective Effect of Tangeretin against Potassium Dichromate-Induced Acute Brain Injury via Modulating AKT/Nrf2 Signaling Pathway in Rats

Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

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Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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1299 Sulforaphane Attenuates Muscle Inflammation in Dystrophin-Deficient Mdx Mice via Nrf2/HO-1 Signaling Pathway

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

Abstract:

Backgrounds: Inflammation is widely distributed in patients with Duchenne muscular dystrophy (DMD), and ultimately leads to progressive deterioration of muscle function with the co-effects of chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzymes, heme oxygenase-1 (HO-1). However, whether Nrf2/HO-1 pathway can attenuate muscle inflammation on DMD remains unknown. The purpose of this study was to determine the anti-inflammatory effects of Sulforaphane (SFN) on DMD. Methods: 4-week-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 4 weeks. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Immune cell infiltration in skeletal muscles was analyzed by H&E staining and immuno-histochemistry. Moreover, the expressions of inflammatory cytokines,pro-inflammatory cytokines and Nrf2/HO-1 pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment increased the expression of muscle phase II enzymes HO-1 in Nrf2 dependent manner. Inflammation in mdx skeletal muscles was reduced by SFN treatment as indicated by decreased immune cell infiltration and lower expressions of the inflammatory cytokines CD45, pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the skeletal muscles of mdx mice. Conclusions: Collectively, these results show that SFN can ameliorate muscle inflammation in mdx mice by Nrf2/HO-1 pathway, which indicates Nrf2/HO-1 pathway may represent a new therapeutic target for DMD.

Keywords: sulforaphane, Nrf2, HO-1, inflammation

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1298 A New Development Pathway And Innovative Solutions Through Food Security System

Authors: Osatuyi Kehinde Micheal

Abstract:

There is much research that has contributed to an improved understanding of the future of food security, especially during the COVID-19 pandemic. A pathway was developed by using a local community kitchen in Muizenberg in western cape province, cape town, south Africa, a case study to map out the future of food security in times of crisis. This kitchen aims to provide nutritious, affordable, plant-based meals to our community. It is also a place of diverse learning, sharing, empowering the volunteers, and growth to support the local economy and future resilience by sustaining our community kitchen for the community. This document contains an overview of the story of the community kitchen on how we create self-sustainability as a new pathway development to sustain the community and reduce Zero hunger in the regional food system. This paper describes the key elements of how we respond to covid-19 pandemic by sharing food parcels and creating 13 soup kitchens across the community to tackle the immediate response to covid-19 pandemic and agricultural systems by growing home food gardening in different homes, also having a consciousness Dry goods store to reduce Zero waste and a local currency as an innovation to reduce food crisis. Insights gained from our article and outreach and their value in how we create adaptation, transformation, and sustainability as a new development pathway to solve any future problem crisis in the food security system in our society.

Keywords: sustainability, food security, community development, adapatation, transformation

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1297 Effects of the Natural Compound on SARS-CoV-2 Spike Protein-Mediated Metabolic Alteration in THP-1 Cells Explored by the ¹H-NMR-Based Metabolomics Approach

Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

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Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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1296 Insight into the Electrocatalytic Activities of Nitrogen-Doped Graphyne and Graphdiyne Families: A First-Principles Study

Authors: Bikram K. Das, Kalyan K. Chattopadhyay

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The advent of 2-D materials in the last decade has induced a fresh spur of growth in fuel cell technology as these materials have some highly promising traits that can be exploited to felicitate Oxygen Reduction Reaction (ORR) in an efficient way. Among the various 2-D carbon materials, graphyne (Gy) and graphdiyne (Gdy)1 with their intrinsic non-uniform charge distribution holds promises in this purpose and it is expected2 that substitutional Nitrogen (N) doping could further enhance their efficiency. In this regard, dispersive force corrected density functional theory is used to map the oxygen reduction reaction (ORR) kinetics of five different kinds of N doped graphyne and graphdiyne systems (namely αGy, βGy, γGy, RGy and 6,6,12Gy and Gdy) in alkaline medium. The best doping site for each of the Gy/ Gdy system is determined comparing the formation energies of the possible doping configurations. Similarly, the best di-oxygen (O₂) adsorption sites for the doped systems are identified by comparing the adsorption energies. O₂ adsorption on all N doped Gy/ Gdy systems is found to be energetically favorable. ORR on a catalyst surface may occur either via the Eley-Rideal (ER) or the Langmuir–Hinschelwood (LH) pathway. Systematic studies performed on the considered systems reveal that all of them favor the ER pathway. Further, depending on the nature of di-oxygen adsorption ORR can follow either associative or dissociative mechanism; the possibility of occurrence of both the mechanisms is tested thoroughly for each N doped Gy/ Gdy. For the ORR process, all the Gy/Gdy systems are observed to prefer the efficient four-electron pathway but the expected monotonically exothermic reaction pathway is found only for N doped 6,6,12Gy and RGy following the associative pathway and for N doped βGy, γGy and Gdy following the dissociative pathway. Further computation performed for these systems reveals that for N doped 6,6,12Gy, RGy, βGy, γGy and Gdy the overpotentials are 1.08 V, 0.94 V, 1.17 V, 1.21 V and 1.04 V respectively depicting N doped RGy is the most promising material, to carry out ORR in alkaline medium, among the considered ones. The stability of the ORR intermediate states with the variation of pH and electrode potentials is further explored with Pourbiax diagrams and the activities of these systems in the alkaline medium are compared with the prior reported B/N doped identical systems for ORR in an acidic medium in terms of a common descriptor.

Keywords: graphdiyne, graphyne, nitrogen-doped, ORR

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1295 Evaluating the Potential of a Fast Growing Indian Marine Cyanobacterium by Reconstructing and Analysis of a Genome Scale Metabolic Model

Authors: Ruchi Pathania, Ahmad Ahmad, Shireesh Srivastava

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Cyanobacteria is a promising microbe that can capture and convert atmospheric CO₂ and light into valuable industrial bio-products like biofuels, biodegradable plastics, etc. Among their most attractive traits are faster autotrophic growth, whole year cultivation using non-arable land, high photosynthetic activity, much greater biomass and productivity and easy for genetic manipulations. Cyanobacteria store carbon in the form of glycogen which can be hydrolyzed to release glucose and fermented to form bioethanol or other valuable products. Marine cyanobacterial species are especially attractive for countries with scarcity of freshwater. We recently identified a marine native cyanobacterium Synechococcus sp. BDU 130192 which has good growth rate and high level of polyglucans accumulation compared to Synechococcus PCC 7002. In this study, firstly we sequenced the whole genome and the sequences were annotated using the RAST server. Genome scale metabolic model (GSMM) was reconstructed through COBRA toolbox. GSMM is a computational representation of the metabolic reactions and metabolites of the target strain. GSMMs construction through the application of Flux Balance Analysis (FBA), which uses external nutrient uptake rates and estimate steady state intracellular and extracellular reaction fluxes, including maximization of cell growth. The model, which we have named isyn942, includes 942 reactions and 913 metabolites having 831 metabolic, 78 transport and 33 exchange reactions. The phylogenetic tree obtained by BLAST search revealed that the strain was a close relative of Synechococcus PCC 7002. The flux balance analysis (FBA) was applied on the model iSyn942 to predict the theoretical yields (mol product produced/mol CO₂ consumed) for native and non-native products like acetone, butanol, etc. under phototrophic condition by applying metabolic engineering strategies. The reported strain can be a viable strain for biotechnological applications, and the model will be helpful to researchers interested in understanding the metabolism as well as to design metabolic engineering strategies for enhanced production of various bioproducts.

Keywords: cyanobacteria, flux balance analysis, genome scale metabolic model, metabolic engineering

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1294 Food Insecurity and Other Correlates of Individual Components of Metabolic Syndrome in Women Living with HIV (WLWH) in the United States

Authors: E. Wairimu Mwangi, Daniel Sarpong

Abstract:

Background: Access to effective antiretroviral therapy in the United States has resulted in the rise in longevity in people living with HIV (PLHIV). Despite the progress, women living with HIV (WLWH) experience increasing rates of cardiometabolic disorders compared with their HIV-negative counterparts. Studies focusing on the predictors of metabolic disorders in this population have largely focused on the composite measure of metabolic syndrome (METs). This study seeks to identify the predictors of composite and individual METs factors in a nationally representative sample of WLWH. In particular, the study also examines the role of food security in predicting METs. Methods: The study comprised 1800 women, a subset of participants from the Women’s Interagency HIV Study (WIHS). The primary exposure variable, food security, was measured using the U.S. 10-item Household Food Security Survey Module. The outcome measures are the five metabolic syndrome indicators (elevated blood pressure [systolic BP > 130 mmHg and diastolic BP ≥ 85 mmHg], elevated fasting glucose [≥ 110 mg/dL], elevated fasting triglyceride [≥ 150 mg/dL], reduced HDL cholesterol [< 50 mg/dL], and waist circumference > 88 cm) and the composite measure - Metabolic Syndrome (METs) Status. Each metabolic syndrome indicator was coded one if yes and 0 otherwise. The values of the five indicators were summed, and participants with a total score of 3 or greater were classified as having metabolic syndrome. Participants classified as having metabolic syndrome were assigned a code of 1 and 0 otherwise for analysis. The covariates accounted for in this study fell into sociodemographic factors and behavioral and health characteristics. Results: The participants' mean (SD) age was 47.1 (9.1) years, with 71.4% Blacks and 10.9% Whites. About a third (33.1%) had less than a high school (HS) diploma, 60.4% were married, 32.8% were employed, and 53.7% were low-income. The prevalence of worst dietary diversity, low, moderate, and high food security were 24.1%, 26.6%, 17.0%, and 56.4%, respectively. The correlate profile of the five individual METs factors plus the composite measure of METs differ significantly, with METs based on HDL having the most correlates (Age, Education, Drinking Status, Low Income, Body Mass Index, and Health Perception). Additionally, metabolic syndrome based on waist circumference was the only metabolic factor where food security was significantly correlated (Food Security, Age, and Body Mass Index). Age was a significant predictor of all five individual METs factors plus the composite METs measure. Except for METs based on Fasting Triglycerides, body mass index (BMI) was a significant correlate of the various measures of metabolic syndrome. Conclusion: High-density Lipoprotein (HDL) cholesterol significantly correlated with most predictors. BMI was a significant predictor of all METs factors except Fasting Triglycerides. Food insecurity, the primary predictor, was only significantly associated with waist circumference.

Keywords: blood pressure, food insecurity, fasting glucose, fasting triglyceride, high-density lipoprotein, metabolic syndrome, waist circumference, women living with HIV

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