Search results for: insulin signaling
463 Coalescence of Insulin and Triglyceride/High Density Lipoprotein Cholesterol Ratio for the Derivation of a Laboratory Index to Predict Metabolic Syndrome in Morbid Obese Children
Authors: Orkide Donma, Mustafa M. Donma
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Morbid obesity is a health threatening condition particularly in children. Generally, it leads to the development of metabolic syndrome (MetS) characterized by central obesity, elevated fasting blood glucose (FBG), triglyceride (TRG), blood pressure values and suppressed high density lipoprotein cholesterol (HDL-C) levels. However, some ambiguities exist during the diagnosis of MetS in children below 10 years of age. Therefore, clinicians are in the need of some surrogate markers for the laboratory assessment of pediatric MetS. In this study, the aim is to develop an index, which will be more helpful during the evaluation of further risks detected in morbid obese (MO) children. A total of 235 children with normal body mass index (N-BMI), with varying degrees of obesity; overweight (OW), obese (OB), MO as well as MetS participated in this study. The study was approved by the Institutional Ethical Committee. Informed consent forms were obtained from the parents of the children. Obesity states of the children were classified using BMI percentiles adjusted for age and sex. For the purpose, tabulated data prepared by WHO were used. MetS criteria were defined. Systolic and diastolic blood pressure values were measured. Parameters related to glucose and lipid metabolisms were determined. FBG, insulin (INS), HDL-C, TRG concentrations were determined. Diagnostic Obesity Notation Model Assessment Laboratory (DONMALAB) Index [ln TRG/HDL-C*INS] was introduced. Commonly used insulin resistance (IR) indices such as Homeostatic Model Assessment for IR (HOMA-IR) as well as ratios such as TRG/HDL-C, TRG/HDL-C*INS, HDL-C/TRG*INS, TRG/HDL-C*INS/FBG, log, and ln versions of these ratios were calculated. Results were interpreted using statistical package program (SPSS Version 16.0) for Windows. The data were evaluated using appropriate statistical tests. The degree for statistical significance was defined as 0.05. 35 N, 20 OW, 47 OB, 97 MO children and 36 with MetS were investigated. Mean ± SD values of TRG/HDL-C were 1.27 ± 0.69, 1.86 ± 1.08, 2.15 ± 1.22, 2.48 ± 2.35 and 4.61 ± 3.92 for N, OW, OB, MO and MetS children, respectively. Corresponding values for the DONMALAB index were 2.17 ± 1.07, 3.01 ± 0.94, 3.41 ± 0.93, 3.43 ± 1.08 and 4.32 ± 1.00. TRG/HDL-C ratio significantly differed between N and MetS groups. On the other hand, DONMALAB index exhibited statistically significant differences between N and all the other groups except the OW group. This index was capable of discriminating MO children from those with MetS. Statistically significant elevations were detected in MO children with MetS (p < 0.05). Multiple parameters are commonly used during the assessment of MetS. Upon evaluation of the values obtained for N, OW, OB, MO groups and for MO children with MetS, the [ln TRG/HDL-C*INS] value was unique in discriminating children with MetS.Keywords: children, index, laboratory, metabolic syndrome, obesity
Procedia PDF Downloads 142462 Erectile Dysfunction among Bangladeshi Men with Diabetes
Authors: Shahjada Selim
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Background: Erectile dysfunction (ED) is an important impediment to quality of life of men. ED is approximate, three times more common in diabetic than non-diabetic men, and diabetic men develop ED earlier than age-matched non-diabetic subjects. Glycemic control and other factors may contribute in developing and or deteriorating ED. Aim: The aim of the study was to determine the prevalence of ED and its risk factors in type 2 diabetic (T2DM) men in Bangladesh. Methods: During 2013-2014, 3980 diabetic men aged 30-69 years were interviewed at the out-patient departments of seven diabetic centers in Dhaka by using the validated Bengali version of the questionnaire of the International index of erectile function (IIEF) for evaluation of baseline erectile function (EF). The indexes indicate a very high correlation between the items and the questionnaire is consistently reliable. Data were analyzed with Chi-squared (χ²) test using SPSS software. P ≤ 0.05 was considered significant. Results: Out of 3790, ED was found in 2046 (53.98%) of T2DM men. The prevalence of ED was increased with age from 10.5% in men aged 30-39 years to 33.6% in those aged over 60 years (P < 0.001). In comparison with patients with reported diabetes lasting ≤ 5 years (26.4%), the prevalence of ED was less than in those with diabetes of 6-11 years (35.3%) and of 12-30 years (42.5%, P <0.001). ED increased significantly in those who had poor glycemic control. The prevalence of ED in patients with good, fair and poor glycemic control was 22.8%, 42.5% and 47.9% respectively (P = 0.004). Treatment modalities (medical nutrition therapy, oral agents, insulin, and insulin plus oral agents) had significant association with ED and its severity (P < 0.001). Conclusion: Prevalence of ED is very high among T2DM men in Bangladesh and can be reduced the burden by improving glycemic status. Glycemic control, duration of diabetes, treatment modalities, increasing age are associated with ED.Keywords: erectile dysfunction, diabetes, men, Bangladesh
Procedia PDF Downloads 258461 Modeling of an Insulin Mircopump
Authors: Ahmed Slami, Med El Amine Brixi Nigassa, Nassima Labdelli, Sofiane Soulimane, Arnaud Pothier
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Many people suffer from diabetes, a disease marked by abnormal levels of sugar in the blood; 285 million people have diabetes, 6.6% of the world adult population (in 2010), according to the International Diabetes Federation. Insulin medicament is invented to be injected into the body. Generally, the injection requires the patient to do it manually. However, in many cases he will be unable to inject the drug, saw that among the side effects of hyperglycemia is the weakness of the whole body. The researchers designed a medical device that injects insulin too autonomously by using micro-pumps. Many micro-pumps of concepts have been investigated during the last two decades for injecting molecules in blood or in the body. However, all these micro-pumps are intended for slow infusion of drug (injection of few microliters by minute). Now, the challenge is to develop micro-pumps for fast injections (1 microliter in 10 seconds) with accuracy of the order of microliter. Recently, studies have shown that only piezoelectric actuators can achieve this performance, knowing that few systems at the microscopic level were presented. These reasons lead us to design new smart microsystems injection drugs. Therefore, many technological advances are still to achieve the improvement of materials to their uses, while going through their characterization and modeling action mechanisms themselves. Moreover, it remains to study the integration of the piezoelectric micro-pump in the microfluidic platform features to explore and evaluate the performance of these new micro devices. In this work, we propose a new micro-pump model based on piezoelectric actuation with a new design. Here, we use a finite element model with Comsol software. Our device is composed of two pumping chambers, two diaphragms and two actuators (piezoelectric disks). The latter parts will apply a mechanical force on the membrane in a periodic manner. The membrane deformation allows the fluid pumping, the suction and discharge of the liquid. In this study, we present the modeling results as function as device geometry properties, films thickness, and materials properties. Here, we demonstrate that we can achieve fast injection. The results of these simulations will provide quantitative performance of our micro-pumps. Concern the spatial actuation, fluid rate and allows optimization of the fabrication process in terms of materials and integration steps.Keywords: COMSOL software, piezoelectric, micro-pump, microfluidic
Procedia PDF Downloads 337460 Competition Between the Effects of Pesticides and Immune-activation on the Expression of Toll Pathway Genes
Authors: Dani Sukkar, Ali Kanso, Philippe Laval-Gilly, Jairo Falla-Angel
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The honeybees' immune system is challenged by different risk factors that induce various responses. However, complex scenarios where bees are exposed to different pesticides simultaneously with immune activation are not well evaluated. The Toll pathway is one of the main signaling pathways studied in invertebrate immune responses, and it is a good indicator of the effect of such complex interactions in addition to key signaling elements of other pathways like Relish of the immune deficiency (IMD) pathway or Eater, the phagocytosis receptor or vitellogenin levels. Honeybee hemocytes extracted from 5th instar larvae were exposed to imidacloprid and/or amitraz with or without the presence of the zymosan a as an immune activator. The gene expression of multiple immune related genes were studied, including spaetzle, Toll, myD88, relish, eater and vitellogenin, by real-time polymerase chain reaction after RNA extraction. The results demonstrated that the Toll pathway is mainly affected by the pesticides; imidacloprid and amitraz, especially by their different combinations. Furthermore, immune activation by zymosan A, a fungal cell-wall component, acts to mitigate to some extent the effect of pesticides on the different levels of the Toll pathway. In addition, imidacloprid, amitraz, and zymosan A have complex and context-specific interactions depending on the levels of immune activation and the pathway evaluated affecting immune-gene expression differently.Keywords: toll pathway, immune modulation, β-glucan, imidacloprid, amitraz, honeybees, immune genes
Procedia PDF Downloads 74459 Uncovering Anti-Hypertensive Obesity Targets and Mechanisms of Metformin, an Anti-Diabetic Medication
Authors: Lu Yang, Keng Po Lai
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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 115458 Renoprotective Effect of Alcoholic Extract of Bacopa monnieri via Inhibition of Advanced Glycation End Products and Oxidative Stress in Stz-Nicotinamide Induced Diabetic Nephropathy
Authors: Lalit Kishore, Randhir Singh
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Diabetic nephropathy (DN) is the major cause of morbidity among diabetic patients. In this study, the effect of Bacopa monnieri Linn. (Brahmi, BM), was studied in a Streptozotocin (STZ)-induced experimental rat model of DN. Diabetic nephropathy was induced in Male Wistar rats (body weight- 300± 10 gms) by single intra-peritoneal injection of STZ (45mg/kg, i.p.) after 15 min of Nicotinamide (230 mg/kg) administration. Different doses of alcoholic extract i.e. 100, 200 and 400 mg/kg was given for 45 days by oral gavage after induction of DN. Blood glucose level, serum insulin, glycosylated haemoglobin, renal parameters (serum urea, uric acid, creatinine and BUN) and lipid profile (total cholesterol, triglycerides, HDL, LDL and VLDL levels) were measured. Concentration of thiobarbituric acid reactive species (TBARS) and levels of antioxidant enzymes of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the kidney, liver and pancreas. At the end of treatment period the alcoholic extract of BM reduced the elevated level of blood glucose, serum insulin, renal parameters, lipid levels, TBARS, AGE’s in kidney and significantly increased body weight, HDL and antioxidant enzymes in dose dependent manner as compared to diabetic control animals. These results suggested the BM possesses significant renoprotective activity.Keywords: AGE's, lipid profile, oxidative stress, renal parameters
Procedia PDF Downloads 313457 Protective Role of Autophagy Challenging the Stresses of Type 2 Diabetes and Dyslipidemia
Authors: Tanima Chatterjee, Maitree Bhattacharyya
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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes
Procedia PDF Downloads 126456 Effects of Egg Yolk Peptide on the Retardation of Bone Growth Induced by Low-Calcium Diets
Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim
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Eggs have long been an important contributor to the nutritional quality of the human, and recognized as a very valuable source of proteins for human nutrition. Egg yolk is composed of various important chemical substances for human health. Growth means not only the increase of body weight but also the elongation of height and the enlargement of each organ's anatomical and morphological size. A calcium shortage causes the growth retardation on the body growth. In this study, we examined the therapeutic effects of egg yolk peptide (EYP) on the retardation of the longitudinal bone growth induced by low-calcium diet (0.05%) in adolescent rats. Low calcium diets were administrated for 15 days. During the last five days, calcium and/or vitamin D and/or EYP were administrated. The body weights, longitudinal bone growth rates, the heights of growth plates, and bone morphogenetic protein (BMP)-2 and insulin-like growth factor (IGF)-1 expressions were measured using histochemical analysis. Low calcium diets caused the significant reduction in body weight gains and the longitudinal bone growth. The heights of growth plates and the expressions of BMP-2 and IGF-1 showed the impairment of body growth as well. Calcium and/or vitamin D administration could not significantly increase the longitudinal bone growth. However, calcium, vitamin D, and EYP administration significantly increased the bone growth, the growth plate height, and BMP-2 and IGF-1 expressions. These results suggest that EYP enhances the longitudinal bone growth in the calcium and/or vitamin D deficiency and it could be a promising agent for the treatment of children suffering from malnutrition.Keywords: egg yolk peptide, low-calcium diet, longitudinal bone growth, morphogenetic protein-2, insulin-like growth factor-1, vitamin D
Procedia PDF Downloads 438455 5-HT2CR Deficiency Causes Affective Disorders by Impairing E/I Balance through Augmenting Hippocampal nNOS-CAPON Coupling
Authors: Hu-Jiang Shi, Li-Juan Zhu
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The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release
Procedia PDF Downloads 57454 Efficacy of Comprehensive Diabetic Care Program with the Reduction of HbA1c in Overweight Type II Diabetes Mellitus Patients: A Retrospective Study
Authors: Rohit Sane, Pravin Ghadigaonkar, Purvi Ahuja, Suvarna Tirmare, Archana Kelhe, Kranti Shinde, Rahul Mandole
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To evaluate the efficacy of Comprehensive Diabetic Care Program with the reduction of HbA1c in overweight Diabetes Mellitus Type II patients retrospectively. Methods: Retrospective study was carried out on 34 overweight type II diabetic patients (Mean Age = 54.58 ±11.38 yrs). A total of 34 patients were enrolled after screening of 68 patients (HbA1c 7-10%). The patients were on concomitant drugs namely insulin (11.76%), DPP-4 inhibitor (17.64%), Biguanide (55.88%), Sulfonylurea (52.94%), thiazolidinedione (11.76%), other medications (20.58%) and no allopathic medications (14.70%). The patients were given Comprehensive Diabetic Care Program consisting of panchkarma procedures namely snehana (external oleation), swedana (passive heat therapy) and basti (enema), which was completed in 15 sittings. During the therapy and next 90 days, the patients followed low carbohydrate and moderate protein & fat diet. The primary endpoint of this study was the evaluation of reduction in HbA1c at the end of the follow-up after 90 days. Results: Thirty-four overweight type II diabetic patients (mean age: 54.58[±11.38], HbA1c[7-10%], 67.64% male and 32.35% female) were enrolled in the study. A significant reduction was observed in HbA1c levels (14.30%, p<0.05) at the end of the 90 days follow-up as compared to baseline. Also, BMI was reduced by 5.87%. There was reduction in the usage of the concomitant drugs namely insulin (2.94%), DPP-4 inhibitor (2.94%), Biguanide (32.35%), Sulfonylurea (35.29%), thiazolidinedione (5.88%), other medications(17.64%) and no allopathic medications (32.35%). Conclusion: The results of the study highlight not only in the reduction of HbA1c, but also in BMI and drug tapering of the CDC program in the overweight type II diabetic patients with HbA1c (7-10%).Keywords: HbA1c, low carb diet, Panchakarma therapy, Type II Diabetes
Procedia PDF Downloads 277453 Interferon-Induced Transmembrane Protein-3 rs12252-CC Associated with the Progress of Hepatocellular Carcinoma by Up-Regulating the Expression of Interferon-Induced Transmembrane Protein 3
Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao
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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin
Procedia PDF Downloads 119452 Effect of Nutrition Education on the Control and Function of Insulin-Dependent Diabetes Patients
Authors: Rahil Sahragard, Mahmoud Hatami, Rostam Bahadori Khalili
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Diabetes is one of the most important health problems in the world and a chronic disease requiring continuous care and therefore, it is necessary for patients to undergo self-care and nutrition education. This study was conducted to evaluate the effect of nutrition education on the metabolic control of diabetic patients in Tehran in 2015. An experimental study was conducted on 100 patients who had previously been approved by a specialist physician for diabetes and at least one year after their onset. At first, patients without any knowledge of the educational program were selected as sample and from them a checklist containing demographic and specific information about diabetes was filled and were taken three fasting blood glucose and three times fasting blood glucose (5 p.m.) Then, the patients received face-to-face training in the same conditions for 2 weeks in a Mehregan hospital of Tehran, and received 3 months of training, while they were fully monitored and during this time, samples that had a cold or blood pressure-related disease or were admitted to the hospital were excluded from the study. After the end of the study, the checklist was filled again and 3 fasting blood glucose and 3 fasting blood glucose samples were taken, the results were statistically analyzed by MC Nemar's statistical test. The research findings were performed on 100 patients 41.7% male and 58.3% women, the range of age was between 22 and 60 years old, with a duration of diabetes ranging from 1 to 15 years. Abnormal fasting blood glucose from 95% to 48.3% (P <0.0001) and non-fasting blood glucose decreased from 91.6% to 71.2% (P <0.001). Research has shown that training on blood glucose control has been successful, therefore, it is recommended that more research is done in the field of education to help patients with diabetes more comfortable.Keywords: nutrition education, diabetes, function, insulin, chronic, metabolic control
Procedia PDF Downloads 129451 Rapid Mitochondrial Reactive Oxygen Species Production Precedes NF-κB Activation and Pro-inflammatory Responses in Macrophages
Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos
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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages
Procedia PDF Downloads 64450 Effect of Zingerone on High-Fructose Diet-Indeuced Metabolic Derangements in Growing Sprague-Dawley Rats
Authors: Nondumiso Lushozi, Busisani Lembede, Eliton Chivandi
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Consumption of fructose increases the risk of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome in children. Zingerone which is found in ginger has antidiabetic and antiobesogenic properties. Therefore, the aim of the study was to investigate the potential of orally administered zingerone to protect growing Sprague-Dawley rats (mimicking growing children) against high-fructose diet-induced metabolic derangements. Forty, 21-day old female Sprague-Dawley rats were randomly allocated and administered the following four treatments for 12 weeks: group I: standard rat chow (SR) + plain water (PW) + plain gelatine cube (PC). group II: SR + 20% (w/v) fructose solution (FS) + PC. group III: SR + FS + 100 mg/kg/day of fenofibrate in gelatine cube. group IV: SR+ FS + 20 mg/kg/day of zingerone in gelatine cube. The rats’ triglyceride, cholesterol, insulin & adiponectin concentration, visceral fat liver lipid content, homoeostasis model assessment of insulin resistance (HOMA-IR) and ability to handle glucose were determined. Oral administration of zingerone significantly increased (P<0.001) visceral fat and liver lipid content (P<0.001), respectively. Results from the study revealed that administration of 20% fructose solution did not induce metabolic dysfunction, however the zingerone treatment increased visceral fat and liver lipid content, all these lipid abnormalities are typical features of the metabolic syndrome, therefore the current study suggests that zingerone has no effect on metabolic dysfunction in adolescent females.Keywords: antidiabetic, metabolic syndrome, zingerone, antiobesogenic
Procedia PDF Downloads 117449 Survey of the Effect of the Probiotic Bacterium Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT/PTEN, and MAPK Signaling Pathways at Co-Culture with KB Oral Cancer Cell Line and HUVEC Cells
Authors: Negar Zaheddoust, Negin Zaheddoust, Abbas Asoudeh-Fard
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Probiotic bacteria have been employed as a novel and less side-effect strategy for anticancer therapy. Since the oral cavity is a host for probiotic and pathogen bacteria to colonize, more investigation is needed to evaluate the effectiveness of this novel adjunctive treatment for oral cancer. We considered Lactobacillus plantarum as a probiotic and Streptococcus mutans as a pathogen bacterium in our study. The aim of this study is to examine the effect of Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT / PTEN, and MAPK signaling pathway, which is involved in apoptosis or survival of oral cancer KB cells. On the other hand, to study the effects of these bacteria on normal cells, we used HUVEC cells. The KB and HUVEC cell lines were co-cultured with Lactobacillus plantarum and Streptococcus mutans isolated from traditional Iranian dairy and dental plaque, respectively. The growth-inhibitory effects of these two bacteria on KB and HUVEC cells were determined by (3-(4, 5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide) MTT assay. MTT results demonstrated that the proliferation of KB cells was affected in a time, dose, and strain-dependent manner. In the following, the examination of induced apoptosis or necrosis in co-cultured KB cells with the best IC50 concentration of the Lactobacillus plantarum and Streptococcus mutans will be analyzed by FACS flow cytometry, and the changes in gene expression of Casp3, AKT / PTEN, MAPK genes will be evaluated using real-time polymerase chain reaction.Keywords: cancer therapy, induced apoptosis, oral cancer, probiotics
Procedia PDF Downloads 242448 Analog Railway Signal Object Controller Development
Authors: Ercan Kızılay, Mustafa Demi̇rel, Selçuk Coşkun
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Railway signaling systems consist of vital products that regulate railway traffic and provide safe route arrangements and maneuvers of trains. SIL 4 signal lamps are produced by many manufacturers today. There is a need for systems that enable these signal lamps to be controlled by commands from the interlocking. These systems should act as fail-safe and give error indications to the interlocking system when an unexpected situation occurs for the safe operation of railway systems from the RAMS perspective. In the past, driving and proving the lamp in relay-based systems was typically done via signaling relays. Today, the proving of lamps is done by comparing the current values read over the return circuit, the lower and upper threshold values. The purpose is an analog electronic object controller with the possibility of easy integration with vital systems and the signal lamp itself. During the study, the EN50126 standard approach was considered, and the concept, definition, risk analysis, requirements, architecture, design, and prototyping were performed throughout this study. FMEA (Failure Modes and Effects Analysis) and FTA (Fault Tree) Analysis) have been used for safety analysis in accordance with EN 50129. Concerning these analyzes, the 1oo2D reactive fail-safe hardware design of a controller has been researched. Electromagnetic compatibility (EMC) effects on the functional safety of equipment, insulation coordination, and over-voltage protection were discussed during hardware design according to EN 50124 and EN 50122 standards. As vital equipment for railway signaling, railway signal object controllers should be developed according to EN 50126 and EN 50129 standards which identify the steps and requirements of the development in accordance with the SIL 4(Safety Integrity Level) target. In conclusion of this study, an analog railway signal object controller, which takes command from the interlocking system, is processed in driver cards. Driver cards arrange the voltage level according to desired visibility by means of semiconductors. Additionally, prover cards evaluate the current upper and lower thresholds. Evaluated values are processed via logic gates which are composed as 1oo2D by means of analog electronic technologies. This logic evaluates the voltage level of the lamp and mitigates the risks of undue dimming.Keywords: object controller, railway electronic, analog electronic, safety, railway signal
Procedia PDF Downloads 91447 Shielding Engineered Islets with Mesenchymal Stem Cells Enhance Survival under Hypoxia by Inhibiting p38 MAPK
Authors: Bhawna Chandravanshi, Ramesh Bhonde
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In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress
Procedia PDF Downloads 254446 The Potential Involvement of Platelet Indices in Insulin Resistance in Morbid Obese Children
Authors: Orkide Donma, Mustafa M. Donma
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Association between insulin resistance (IR) and hematological parameters has long been a matter of interest. Within this context, body mass index (BMI), red blood cells, white blood cells and platelets were involved in this discussion. Parameters related to platelets associated with IR may be useful indicators for the identification of IR. Platelet indices such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) are being questioned for their possible association with IR. The aim of this study was to investigate the association between platelet (PLT) count as well as PLT indices and the surrogate indices used to determine IR in morbid obese (MO) children. A total of 167 children participated in the study. Three groups were constituted. The number of cases was 34, 97 and 36 children in the normal BMI, MO and metabolic syndrome (MetS) groups, respectively. Sex- and age-dependent BMI-based percentile tables prepared by World Health Organization were used for the definition of morbid obesity. MetS criteria were determined. BMI values, homeostatic model assessment for IR (HOMA-IR), alanine transaminase-to-aspartate transaminase ratio (ALT/AST) and diagnostic obesity notation model assessment laboratory (DONMA-lab) index values were computed. PLT count and indices were analyzed using automated hematology analyzer. Data were collected for statistical analysis using SPSS for Windows. Arithmetic mean and standard deviation were calculated. Mean values of PLT-related parameters in both control and study groups were compared by one-way ANOVA followed by Tukey post hoc tests to determine whether a significant difference exists among the groups. The correlation analyses between PLT as well as IR indices were performed. Statistically significant difference was accepted as p-value < 0.05. Increased values were detected for PLT (p < 0.01) and PCT (p > 0.05) in MO group compared to those observed in children with N-BMI. Significant increases for PLT (p < 0.01) and PCT (p < 0.05) were observed in MetS group in comparison with the values obtained in children with N-BMI (p < 0.01). Significantly lower MPV and PDW values were obtained in MO group compared to the control group (p < 0.01). HOMA-IR (p < 0.05), DONMA-lab index (p < 0.001) and ALT/AST (p < 0.001) values in MO and MetS groups were significantly increased compared to the N-BMI group. On the other hand, DONMA-lab index values also differed between MO and MetS groups (p < 0.001). In the MO group, PLT was negatively correlated with MPV and PDW values. These correlations were not observed in the N-BMI group. None of the IR indices exhibited a correlation with PLT and PLT indices in the N-BMI group. HOMA-IR showed significant correlations both with PLT and PCT in the MO group. All of the three IR indices were well-correlated with each other in all groups. These findings point out the missing link between IR and PLT activation. In conclusion, PLT and PCT may be related to IR in addition to their identities as hemostasis markers during morbid obesity. Our findings have suggested that DONMA-lab index appears as the best surrogate marker for IR due to its discriminative feature between morbid obesity and MetS.Keywords: children, insulin resistance, metabolic syndrome, plateletcrit, platelet indices
Procedia PDF Downloads 99445 Effect of Chronic Exposure to Diazinon on Glucose Homeostasis and Oxidative Stress in Pancreas of Rats and the Potential Role of Mesna in Ameliorating This Effect
Authors: Azza El-Medany, Jamila El-Medany
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Residential and agricultural pesticide use is widespread in the world. Their extensive and indiscriminative use, in addition with their ability to interact with biological systems other than their primary targets constitute a health hazards to both humans and animals. The toxic effects of pesticides include alterations in metabolism; there is a lack of knowledge that organophosphates can cause pancreatic toxicity. The primary goal of this work is to study the effects of chronic exposure to Diazinon an organophosphate used in agriculture on pancreatic tissues and evaluate the ameliorating effect of Mesna as antioxidant on the toxicity of Diazinon on pancreatic tissues.40 adult male rats, their weight ranged between 300-350 g. The rats were classified into three groups; control (10 rats) was received corn oil at a dose of 1 0 mg/kg/day by gavage once a day for 2 months. Diazinon (15 rats) was received Diazinon at a dose of 10 mg/kg/day dissolved in corn oil by gavage once a day for 2 months. Treated group (15 rats), were received Mesna 180mg/kg once a week by gavage 15 minutes before administration of Diazinon for 2 months. At the end of the experiment, animals were anesthetized, blood samples were taken by cardiac puncture for glucose and insulin assays and pancreas was removed and divided into 3 portions; first portion for histopathological study; second portion for ultrastructural study; third portion for biochemical study using Elisa Kits including determination of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), myeloperoxidase activity (MPO), interleukin 1β (IL-1β). A significant increase in the levels of MDA, TNF-α, MPO activity, IL-1β, serum glucose levels in the toxicated group with Diazinon were observed, while a significant reduction was noticed in GSH in serum insulin levels. After treatment with Mesna a significant reduction was observed in the previously mentioned parameters except that there was a significant rise in GSH in insulin levels. Histopathological and ultra-structural studies showed destruction in pancreatic tissues and β cells were the most affected cells among the injured islets as compared with the control group. The current study try to spot light about the effects of chronic exposure to pesticides on vital organs as pancreas also the role of oxidative stress that may be induced by them in evoking their toxicity. This study shows the role of antioxidant drugs in ameliorating or preventing the toxicity. This appears to be a promising approach that may be considered as a complementary treatment of pesticide toxicity.Keywords: Diazinon, reduced glutathione, myeloperoxidase activity, tumor necrosis factor α, Mesna
Procedia PDF Downloads 233444 Effects of Nanoencapsulated Echinacea purpurea Ethanol Extract on the Male Reproductive Function in Streptozotocin-Induced Diabetic Rats
Authors: Jia-Ling Ho, Xiu-Ru Zhang, Zwe-Ling Kong
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Diabetes mellitus (DM) is a major health problem that affects patients’ life quality throughout the world due to its many complications. It characterized by chronic hyperglycemia with oxidative stress, which impaired male reproductive function. Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for normal spermatogenesis and protects against diabetes-induced germ cell apoptosis. Echinacea purpurea ethanol extract (EE), which contain phenolic acid and isobutylamide, had been proven to have antidiabetic property. Silica-chitosan nanoparticles (Nano-CS) has drug delivery and controlled release properties. This study aims to investigate whether silica-chitosan nanoparticles encapsulated EE (Nano-EE) had more ameliorating male infertility by analyzing the effect of testicular FGF21. The Nano-EE was characterized before used to treatment the diabetic rat model. Male Sprague-Dawley (SD) rats were obtained and divided into seven groups. A group was no induced Streptozotocin (STZ), marked as normal group. Diabetic rats were induced into diabetes by STZ (33 mg/kg). A diabetic group was no treatment with sample (diabetic control group), and other groups were treatment by Nano-CS (465 mg/kg), Nano-EE (93, 279, 465 mg/kg), and metformin (Met) (200 mg/kg) used as reference drug for 7 weeks. Our results indicated that the average nanoparticle size and zeta potential of Nano-EE were 2630 nm and -21.3 mV, respectively. The encapsulation ratio of Nano-EE was about 70%. It also confirmed the antioxidative activity was unchanged by comparing the DPPH and ABTS scavenging of Nano-EE and EE. In vivo test, Nano-EE can improve the STZ induced hyperglycemia, insulin resistance, and plasma FGF21 levels. Nano-EE has increased sperm motility, mitochondria membrane potential (MMP), plasma testosterone level, and reduction of abnormal sperm, nitric oxide (NO), superoxide production as well as reactive oxygen species (ROS). In addition, in plasma antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) was increased whereas pro-inflammatory cytokines TNF-α, and IL-1β were decreased. Further, in testis, protein content of FGF21, PGC-1α, and SIRT1 were improved. Nano-EE might improve diabetes-induced down-regulation of testicular FGF21 and SIRT1/PGC-1α signaling hence maintain spermatogenesis.Keywords: diabetes mellitus, Echinacea purpurea, reproductive dysfunction, silica-chitosan nanoparticles
Procedia PDF Downloads 186443 Diabetes Mellitus and Blood Glucose Variability Increases the 30-day Readmission Rate after Kidney Transplantation
Authors: Harini Chakkera
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Background: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts with hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission. Methods: Data on first-time solitary kidney transplantations were retrieved between September 2015 to December 2018. Information was linked to the electronic health record to determine a diagnosis of diabetes mellitus and extract glucometeric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on five bootstrapped partitions of the data to ensure statistical significance. Results: The cohort included 1036 patients who received kidney transplantation, and 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average AUC of 77.3% (95% CI 75.30-79.3%). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, and minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia and recipient and donor BMI values as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed. Conclusions: Suboptimal glucose metrics during hospitalization after kidney transplantation is associated with an increased risk for 30-day hospital readmission. Optimizing the hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission.Keywords: kidney, transplant, diabetes, insulin
Procedia PDF Downloads 77442 Investigation of Possible Behavioural and Molecular Effects of Mobile Phone Exposure on Rats
Authors: Ç. Gökçek-Saraç, Ş. Özen, N. Derin
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The N-methyl-D-aspartate (NMDA)-dependent pathway is the major intracellular signaling pathway implemented in both short- and long-term memory formation in the hippocampus which is the most studied brain structure because of its well documented role in learning and memory. However, little is known about the effects of RF-EMR exposure on NMDA receptor signaling pathway including activation of protein kinases, notably Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα). The aim of the present study was to investigate the effects of acute and chronic 900 MHz RF-EMR exposure on both passive avoidance behaviour and hippocampal levels of CaMKIIα and its phosphorylated form (pCaMKIIα). Rats were divided into the following groups: Sham rats, and rats exposed to 900 MHz RF-EMR for 2 h/day for 1 week (acute group) or 10 weeks (chronic group), respectively. Passive avoidance task was used as a behavioural method. The hippocampal levels of selected kinases were measured using Western Blotting technique. The results of passive avoidance task showed that both acute and chronic exposure to 900 MHz RF-EMR can impair passive avoidance behaviour with minor effects on chronic group of rats. The analysis of western blot data of selected protein kinases demonstrated that hippocampal levels of CaMKIIα and pCaMKIIα were significantly higher in chronic group of rats as compared to acute groups. Taken together, these findings demonstrated that different duration times (1 week vs 10 weeks) of 900 MHz RF-EMR exposure have different effects on both passive avoidance behaviour of rats and hippocampal levels of selected protein kinases.Keywords: hippocampus, protein kinase, rat, RF-EMR
Procedia PDF Downloads 252441 Opuntia ficus-indica var. Saboten Stimulates Adipogenesis, Lipolysis, and Glucose Uptake in 3T3-L1 Adipocytes
Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem
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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus
Procedia PDF Downloads 394440 CP-96345 Rregulates Hydrogen Sulphide Induced TLR4 Signaling Pathway Adhesion Molecules in Caerulein Treated Pancreatic Acinar Cells
Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia
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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis
Procedia PDF Downloads 269439 Predicting High-Risk Endometrioid Endometrial Carcinomas Using Protein Markers
Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein
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The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage
Procedia PDF Downloads 218438 IL-33 Production in Murine Macrophages via PGE2-E Prostanoid Receptor 2/4 Signaling
Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce
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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.Keywords: bone marrow macrophages, EPAC, IL-33, PGE2
Procedia PDF Downloads 177437 Smart Coating for Enhanced Corneal Healing via Delivering Progranulin
Authors: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang
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The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells
Procedia PDF Downloads 48436 Effectively Improving Cognition, Behavior, and Attitude of Diabetes Inpatients through Nutritional Education
Authors: Han Chih Feng, Yi-Cheng Hou, Jing-Huei Wu
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Diabetes is a chronic disease. Nutrition knowledge and skills enable individuals with type 2 diabetes to optimize metabolic self-management and quality of life. This research studies the effect of nutritional education on diabetes inpatients in terms of their cognition, behavior, and attitude. The participants are inpatients diagnosed with diabetes at Taipei Tzu Chi Hospital. A total of 103 participants, 58 male, and 45 females, enrolled in the research between January 2018 and July 2018. The research evaluates cognition, behavior, and attitude level before and after nutritional education conducted by dietitians. The result shows significant improvement in actual consumption (2.5 ± 1.4 vs 3.8 ± 0.7; p<.001), diet control motivation (2.7 ± 0.8 vs 3.4 ± 0.6; p<.001), correct nutrition concept (1.2± 0.4 vs 2.4 ± 0.5; p<.001), learning willingness (2.7± 0.9 vs 3.4 ± 0.6; p<.001), cognitive behaviors (1.4 ± 0.5 vs 2.9 ± 0.7; p<.001). AC sugar (278.5 ± 321.5 vs 152.2 ± 49.1; p<.001) and HbA1C (10.3 ± 2.6 vs 8.6 ± 1.9; p<.001) are significant improvement after nutritional education. After nutritional education, participants oral hypoglycemic agents increased from 16 (9.2%) to 33 (19.0%), insulin decreased from 75 (43.1%) to 68 (39.1%), and hypoglycemic drugs combined with insulin decreased from 83 (47.7%) to 73 (42.0%).Further analysis shows that female inpatients have significant improvement in diet control motivation (3.91 ± 0.85 vs 4.44 ± 0.59; p<0.000), correct nutrition concept (3.24± 0.48 vs 4.47± 0.51; p<0.000), learning willingness (3.89 ± 0.86 vs 4.44 ± 0.59; p<0.000) and cognitive behaviors (2.42 ± 0.58 vs 4.02 ± 0.69; p<0.000); male inpatients have significant improvement in actual food intake (4.41± 0.92 vs 3.97 ± 0.42; p<0.000), diet control motivation (3.62 ± 0.86 vs 4.29 ± 0.62; p<0.000), correct nutrition concept (3.26 ± 0.44 vs 4.36 ± 0.49; p<0.000), learning willingness (3.72± 0.93 vs 4.33± 0.63; p<0.000) and cognitive behaviors (2.45± 0.54 vs 4.03± 0.77; p<0.000). In conclusion, nutritional education proves effective, regardless of gender, in improving an inpatient’s cognition, behavior, and attitude toward diabetes self-management.Keywords: diabetes, nutrition education, actual consumption, diet control motivation, nutrition concept, learning willingness, cognitive behaviors
Procedia PDF Downloads 85435 Supplementation of Annatto (Bixa orellana)-Derived δ-Tocotrienol Produced High Number of Morula through Increased Expression of 3-Phosphoinositide-Dependent Protein Kinase-1 (PDK1) in Mice
Authors: S. M. M. Syairah, M. H. Rajikin, A. R. Sharaniza
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Several embryonic cellular mechanism including cell cycle, growth and apoptosis are regulated by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The goal of present study is to determine the effects of annatto (Bixa orellana)-derived δ-tocotrienol (δ-TCT) on the regulations of PI3K/Akt genes in murine morula. Twenty four 6-8 week old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) received tocopherol stripped corn oil, G2 was given 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers), G3 was given 60 mg/kg/day of pure δ-TCT (>98% purity) and G4 received 60 mg/kg/day α-TOC. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. About fifty morula from each group were used in the gene expression analyses using Affymetrix QuantiGene Plex 2.0 Assay. Present data showed a significant increase (p<0.05) in the average number (mean + SEM) of morula produced in G2 (26.0 + 0.45), G3 (23.0 + 0.63) and G4 (25.0 + 0.73) compared to control group (G1 – 16.0 + 0.63). This is parallel with the high expression of PDK1 gene with increase of 2.75-fold (G2), 3.07-fold (G3) and 3.59-fold (G4) compared to G1 (1.78-fold). From the present data, it can be concluded that supplementation with δ-TCT(s) and α-TOC induced high expression of PDK1 in G2-G4 which enhanced the PI3K/Akt signaling activity, resulting in the increased number of morula.Keywords: delta-tocotrienol, embryonic development, nicotine, vitamin E
Procedia PDF Downloads 423434 Interaction of GCN5L1 with WHAMM and KIF5B Regulates Autolysosome Tubulation
Authors: Allen Seylani
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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 151