Search results for: diabetic mice
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 928

Search results for: diabetic mice

118 dynr.mi: An R Program for Multiple Imputation in Dynamic Modeling

Authors: Yanling Li, Linying Ji, Zita Oravecz, Timothy R. Brick, Michael D. Hunter, Sy-Miin Chow

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Assessing several individuals intensively over time yields intensive longitudinal data (ILD). Even though ILD provide rich information, they also bring other data analytic challenges. One of these is the increased occurrence of missingness with increased study length, possibly under non-ignorable missingness scenarios. Multiple imputation (MI) handles missing data by creating several imputed data sets, and pooling the estimation results across imputed data sets to yield final estimates for inferential purposes. In this article, we introduce dynr.mi(), a function in the R package, Dynamic Modeling in R (dynr). The package dynr provides a suite of fast and accessible functions for estimating and visualizing the results from fitting linear and nonlinear dynamic systems models in discrete as well as continuous time. By integrating the estimation functions in dynr and the MI procedures available from the R package, Multivariate Imputation by Chained Equations (MICE), the dynr.mi() routine is designed to handle possibly non-ignorable missingness in the dependent variables and/or covariates in a user-specified dynamic systems model via MI, with convergence diagnostic check. We utilized dynr.mi() to examine, in the context of a vector autoregressive model, the relationships among individuals’ ambulatory physiological measures, and self-report affect valence and arousal. The results from MI were compared to those from listwise deletion of entries with missingness in the covariates. When we determined the number of iterations based on the convergence diagnostics available from dynr.mi(), differences in the statistical significance of the covariate parameters were observed between the listwise deletion and MI approaches. These results underscore the importance of considering diagnostic information in the implementation of MI procedures.

Keywords: dynamic modeling, missing data, mobility, multiple imputation

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117 Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study

Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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116 From Dog to Dog: Potential Probiotic and Immunomodulatory Strains Isolated from Canine Milk

Authors: Paula Buldres, Jorge Toledo

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Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.

Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics

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115 Treatment of Histopathological Symptoms in N-Nitrosopyrrolidine Induced Changes in Lung Tissue by Isolated Flavonoid from Indigofera tinctoria

Authors: Aastha Agarwal, Veena Sharma

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N-nitrosopyrollidine or NPYR is a tobacco-specific nitrosamine which upon intoxicated causes abnormal production of Reactive Oxygen Species disrupt the endogenous antioxidant system. The study was designed to evaluate the histological changes in lung tissue of Mus musculus in NPYR administered lungs and effect of isolated flavonoid 3,6-dihydroxy-(3’,4’,7’-trimethoxyphenyl)-chromen-4-one-7-glucoside (ITC) from experimental plant Indigofera tinctorial. Post treatment with isolated compound significantly restored the abnormal symptoms and changes in pulmonary tissue. Transverse section of mouse lung in control animals appeared as a thin lace. Histologically, most of the lung was arranged as alveoli which were thin walled structures made up of single layered squamous epithelial cells. In the transverse section of lung at 100 X will clearly show the component of alveoli, surround by a thin layer of connective tissue and blood vessels. Smaller bronchioles were lined by cuboidal epithelial cells while larger bronchioles were lined by ciliated columnar epithelium layer while in NPYR intoxicated lungs signs of vast pulmonary damages and carcinogenesis as alveolar damage, necrosis, DADs or defused alveolar damages hyperplasia, metaplasia, dysplasia and next stage of carcinogenesis were revealed. Treatment with ITC showed the significant positive changes in the lung tissue due to the side hydroxyl and methoxy groups in its structure which help in combating oxidative injuries and give protection from the free radicals generated during the metabolism of NPYR in body. Thus, histopathological analysis confirms the development of the cancerous conditions in the lung tissue in mice model and the protective effects of ITC.

Keywords: flavonoid, histopathology, Indigofera tinctoria, lung

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114 Formulation and Evaluation of Metformin Hydrochloride Microparticles via BÜCHI Nano-Spray Dryer B-90

Authors: Tamer Shehata

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Recently, nanotechnology acquired a great interest in the field of pharmaceutical production. Several pharmaceutical equipment were introduced into the research field for production of nanoparticles, among them, BÜCHI’ fourth generation nano-spray dryer B-90. B-90 is specialized with single step of production and drying of nano and microparticles. Currently, our research group is investigating several pharmaceutical formulations utilizing BÜCHI Nano-Spray Dryer B-90 technology. One of our projects is the formulation and evaluation of metformin hydrochloride mucoadhesive microparticles for treatment of type 2-diabetis. Several polymers were investigated, among them, gelatin and sodium alginate. The previous polymers are natural polymers with mucoadhesive properties. Preformulation studies such as atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension were performed. Postformulation characters such as particle size, flowability, surface scan and dissolution profile were evaluated. Finally, the pharmacological activity of certain selected formula was evaluated in streptozotocin-induced diabetic rats. B-90’spray head was 7 µm hole heated to 120 with air flow rate 3.5 mL/min. The viscosity of the solution was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Successfully, discrete, non-aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and Sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula showed a significant reduction of blood glucose level over 24 h. In conclusion, mucoadhesive metformin hydrochloride microparticles obtained from B-90 could offer a convenient dosage form with enhanced hypoglycemic activity.

Keywords: mucoadhesive, microparticles, metformin hydrochloride, nano-spray dryer

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113 Tocotrienol Rich Fraction in Nicotine-Induced Embryos: Cytoskeletal Changes of Actin and Tubulin

Authors: Nurul Hamirah Kamsani, Mohd Hamim Rajikin, Nor Ashikin Mohamed Noor Khan, Sharaniza Abdul Rahim

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Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. Under influence of nicotine, the cytoskeletal organization may be subjected to oxidative stress (OS) insult and cause alteration. Tocotrienol-rich fraction (TRF) is proven to enhance fertility better than the other sub-group of Vitamin E, tocopherols (TCPs). The objective of this study was to evaluate the effects of TRF on 1) actin and tubulin of 2- and 8-cell murine embryos and 2) the regulation of reactive oxygen species (ROS)-scavenging enzymes; induced by nicotine. Twenty four female Balb/C were subjected to either subcutaneous (sc) injection of 0.9% NaCl; sc injection of 3.0 mg/kg bw/day nicotine; sc injection of 3.0 mg/kg bw/day nicotine + oral gavage (OG) of 60 mg/kg bw/day TRF; or OG of 60 mg/kg bw/day TRF for 7 consecutive days. After superovulation and mating, animals were euthanized. 2-cell developing embryos were retrieved. 50% of the retrieved embryos were visualized under confocal laser staining microscopy (CLSM) for alterations of actin and tubulin. The remaining amount of embryos was cultured in vitro until 8-cell stage followed by CLSM visualization. Blood plasma was subjected to OS assays. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined and analysed accordingly. At both 2- and 8-cell developing stages, actin intensities were significantly reduced in the nicotine group (p<0.001). After the intervention, actin intensity was significantly increased compared to that of the nicotine group (p<0.001). The same trend was seen in tubulin at both cell stages. TRF has minimized the deleterious effects of nicotine in actin and tubulin of both 2- and 8-cell developmental stages during pre-implantation embryonic development in mice in vitro. Levels of endogenous anti-oxidative enzymes were sustained close to control accompanied by decreased levels of OS biomarker.

Keywords: actin, nicotine, pre-implantation embryos, tocotrienol rich fraction, tubulin

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112 Teratogenic Effect of Bisphenol A in Development of Balb/C Mouse

Authors: Nazihe Sedighi, Mohsen Nokhbatolphoghaei

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Bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics. Due to having properties such as transparency, heat and impact resistance, it is used widely in medicine, sorts, electronic components, and food containers. It is also used in the production of resins which is applied for lining cans. BPA releases from resins and polycarbonate when it is heated or continuously used the containers from which BPA can enter the body. There are several reports indicating the presence of BPA in the placenta, amniotic fluid, and the embryo itself. While researchers investigated the teratogenic effect of BPA on embryos, very limited work has been done on the effects of BPA when applied from early stages of development. In this study, The teratogenic effect of BPA was investigated at earliest preimplantation (day zero) through day 15.5 of the development of Balb/C mouse embryos. After ensuring the pregnancy via observing vaginal plug, Pregnant mice were divided into five groups. For the three experimental groups, the amount of 500, 750, and 1000 mg/kg/d Bisphenol A was given orally according to body weight. The sham group that was treated with sesame oil, which was used as vehicle and control group remained intact. On day 18.5 of gestation, embryos were removed from the uterus. Randomly half of the embryo were fixed in Bouin for tissue analysis. The other half were prepared for skeletal system staining using Alizarin Red and alcian blue dies. The results showed that the embryonic weight and the crown-rump length of embryos decreased significantly (P < 0.05) in all experimental groups compared to the control group and the sham. In this study, skeletal abnormalities such as delay in ossification of skull and limbs as well as the deviation in the backbone were seen. This research suggests that pregnant mothers need to be aware of possible teratogenic effects of BPA at any stage of pregnancy especially from early to mid stages. In this case, pregnant mothers may need to stop using any manufacture of polycarbonate plastics, as a container for food or drinking.

Keywords: bisphenol A, development, polycarbonate plastic, skeletal system, teratogenicity

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111 Anti-Obesity Activity of Garcinia xanthochymus: Biochemical Characterization and In vivo Studies in High Fat Diet-Rat Model

Authors: Mahesh M. Patil, K. A. Anu-Appaiah

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Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.

Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR

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110 Elevated Creatinine Clearance and Normal Glomerular Filtration Rate in Patients with Systemic Lupus erythematosus

Authors: Stoyanka Vladeva, Elena Kirilova, Nikola Kirilov

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Background: The creatinine clearance is a widely used value to estimate the GFR. Increased creatinine clearance is often called hyperfiltration and is usually seen during pregnancy, patients with diabetes mellitus preceding the diabetic nephropathy. It may also occur with large dietary protein intake or with plasma volume expansion. Renal injury in lupus nephritis is known to affect the glomerular, tubulointerstitial, and vascular compartment. However high creatinine clearance has not been found in patients with SLE, Target: Follow-up of creatinine clearance values in patients with systemic lupus erythematosus without history of kidney injury. Material and methods: We observed the creatinine, creatinine clearance, GFR and dipstick protein values of 7 women (with a mean age of 42.71 years) with systemic lupus erythematosus. Patients with active lupus have been monthly tested in the period of 13 months. Creatinine clearance has been estimated by Cockcroft-Gault Equation formula in ml/sec. GFR has been estimated by MDRD formula (The Modification of Diet in renal Disease) in ml/min/1.73 m2. Proteinuria has been defined as present when dipstick protein > 1+.Results: In all patients without history of kidney injury we found elevated creatinine clearance levels, but GFRremained within the reference range. Two of the patients were in remission while the other five patients had clinically and immunologically active Lupus. Three of the patients had a permanent presence of high creatinine clearance levels and proteinuria. Two of the patients had periodically elevated creatinine clearance without proteinuria. These results show that kidney disturbances may be caused by the vascular changes typical for SLE. Glomerular hyperfiltration can be result of focal segmental glomerulosclerosis caused by a reduction in renal mass. Probably lupus nephropathy is preceded not only by glomerular vascular changes, but also by tubular vascular changes. Using only the GFR is not a sufficient method to detect these primary functional disturbances. Conclusion: For early detection of kidney injury in patients with SLE we determined that the follow up of creatinine clearance values could be helpful.

Keywords: systemic Lupus erythematosus, kidney injury, elevated creatinine clearance level, normal glomerular filtration rate

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109 Preparation and Characterization of Dendrimer-Encapsulated Ytterbium Nanoparticles to Produce a New Nano-Radio Pharmaceutical

Authors: Aghaei Amirkhizi Navideh, Sadjadi Soodeh Sadat, Moghaddam Banaem Leila, Athari Allaf Mitra, Johari Daha Fariba

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Dendrimers are good candidates for preparing metal nanoparticles because they can structurally and chemically well-defined templates and robust stabilizers. Poly amidoamine (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized in pharmaceutical industry. In addition, encapsulated nanoparticle surfaces are accessible to substrates so that catalytic reactions can be carried out. For preparation of dendimer-metal nanocomposite, a dendrimer solution containing an average of 55 Yb+3 ions per dendrimer was prepared. Prior to reduction, the pH of this solution was adjusted to 7.5 using NaOH. NaBH4 was used to reduce the dendrimer-encapsulated Yb+3 to the zerovalent metal. The pH of the resulting solution was then adjusted to 3, using HClO4, to decompose excess BH4-. The UV-Vis absorption spectra of the mixture were recorded to ensure the formation of Yb-G5-NH2 complex. High-resolution electron microscopy (HRTEM) and size distribution results provide additional information about dendimer-metal nanocomposite shape, size, and size distribution of the particles. The resulting mixture was irradiated in Tehran Research Reactor 2h and neutron fluxes were 3×1011 n/cm2.Sec and the specific activity was 7MBq. Radiochemical and chemical and radionuclide quality control testes were carried. Gamma Spectroscopy and High-performance Liquid Chromatography HPLC, Thin-Layer Chromatography TLC were recorded. The injection of resulting solution to solid tumor in mice shows that it could be resized the tumor. The studies about solid tumors and nano composites show that ytterbium encapsulated-dendrimer radiopharmaceutical could be introduced as a new therapeutic for the treatment of solid tumors.

Keywords: nano-radio pharmaceutical, ytterbium, PAMAM, dendrimers

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108 A Systems Approach to Targeting Cyclooxygenase: Genomics, Bioinformatics and Metabolomics Analysis of COX-1 -/- and COX-2-/- Lung Fibroblasts Providing Indication of Sterile Inflammation

Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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107 Evaluation of Hepatic Metabolite Changes for Differentiation Between Non-Alcoholic Steatohepatitis and Simple Hepatic Steatosis Using Long Echo-Time Proton Magnetic Resonance Spectroscopy

Authors: Tae-Hoon Kim, Kwon-Ha Yoon, Hong Young Jun, Ki-Jong Kim, Young Hwan Lee, Myeung Su Lee, Keum Ha Choi, Ki Jung Yun, Eun Young Cho, Yong-Yeon Jeong, Chung-Hwan Jun

Abstract:

Purpose: To assess the changes of hepatic metabolite for differentiation between non-alcoholic steatohepatitis (NASH) and simple steatosis on proton magnetic resonance spectroscopy (1H-MRS) in both humans and animal model. Methods: The local institutional review board approved this study and subjects gave written informed consent. 1H-MRS measurements were performed on a localized voxel of the liver using a point-resolved spectroscopy (PRESS) sequence and hepatic metabolites of alanine (Ala), lactate/triglyceride (Lac/TG), and TG were analyzed in NASH, simple steatosis and control groups. The group difference was tested with the ANOVA and Tukey’s post-hoc tests, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolic concentration and pathologic grades or non-alcoholic fatty liver disease(NAFLD) activity scores were assessed by the Pearson’s correlation. Results: Patient with NASH showed the elevated Ala(p<0.001), Lac/TG(p < 0.001), TG(p < 0.05) concentration when compared with patients who had simple steatosis and healthy controls. The NASH patients were higher levels in Ala(mean±SEM, 52.5±8.3 vs 2.0±0.9; p < 0.001), Lac/TG(824.0±168.2 vs 394.1±89.8; p < 0.05) than simple steatosis. The area under the ROC curve to distinguish NASH from simple steatosis was 1.00 (95% confidence interval; 1.00, 1.00) with Ala and 0.782 (95% confidence interval; 0.61, 0.96) with Lac/TG. The Ala and Lac/TG levels were well correlated with steatosis grade, lobular inflammation, and NAFLD activity scores. The metabolic changes in human were reproducible to a mice model induced by streptozotocin injection and a high-fat diet. Conclusion: 1H-MRS would be useful for differentiation of patients with NASH and simple hepatic steatosis.

Keywords: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, 1H MR spectroscopy, hepatic metabolites

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106 Coffee Consumption and Glucose Metabolism: a Systematic Review of Clinical Trials

Authors: Caio E. G. Reis, Jose G. Dórea, Teresa H. M. da Costa

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Objective: Epidemiological data shows an inverse association of coffee consumption with risk of type 2 diabetes mellitus. However, the clinical effects of coffee consumption on the glucose metabolism biomarkers remain controversial. Thus, this paper reviews clinical trials that evaluated the effects of coffee consumption on glucose metabolism. Research Design and Methods: We identified studies published until December 2014 by searching electronic databases and reference lists. We included randomized clinical trials which the intervention group received caffeinated and/or decaffeinated coffee and the control group received water or placebo treatments and measured biomarkers of glucose metabolism. The Jadad Score was applied to evaluate the quality of the studies whereas studies that scored ≥ 3 points were considered for the analyses. Results: Seven clinical trials (total of 237 subjects) were analyzed involving adult healthy, overweight and diabetic subjects. The studies were divided in short-term (1 to 3h) and long-term (2 to 16 weeks) duration. The results for short-term studies showed that caffeinated coffee consumption may increase the area under the curve for glucose response, while for long-term studies caffeinated coffee may improve the glycemic metabolism by reducing the glucose curve and increasing insulin response. These results seem to show that the benefits of coffee consumption occur in the long-term as has been shown in the reduction of type 2 diabetes mellitus risk in epidemiological studies. Nevertheless, until the relationship between long-term coffee consumption and type 2 diabetes mellitus is better understood and any mechanism involved identified, it is premature to make claims about coffee preventing type 2 diabetes mellitus. Conclusion: The findings suggest that caffeinated coffee may impairs glucose metabolism in short-term but in the long-term the studies indicate reduction of type 2 diabetes mellitus risk. More clinical trials with comparable methodology are needed to unravel this paradox.

Keywords: coffee, diabetes mellitus type 2, glucose, insulin

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105 Precise Spatially Selective Photothermolysis Skin Treatment by Multiphoton Absorption

Authors: Yimei Huang, Harvey Lui, Jianhua Zhao, Zhenguo Wu, Haishan Zeng

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Conventional laser treatment of skin diseases and cosmetic surgery is based on the principle of one-photon absorption selective photothermolysis which relies strongly on the difference in the light absorption between the therapeutic target and its surrounding tissue. However, when the difference in one-photon absorption is not sufficient, collateral damage would occur due to indiscriminate and nonspecific tissue heating. To overcome this problem, we developed a spatially selective photothermolysis method based on multiphoton absorption in which the heat generation is restricted to the focal point of a tightly focused near-infrared femtosecond laser beam aligned with the target of interest. A multimodal optical microscope with co-registered reflectance confocal imaging (RCM), two-photon fluorescence imaging (TPF), and second harmonic generation imaging (SHG) capabilities was used to perform and monitor the spatially selective photothermolysis. Skin samples excised from the shaved backs of euthanized NODSCID mice were used in this study. Treatments were performed by focusing and scaning the laser beam in the dermis with a 50µm×50µm target area. Treatment power levels of 200 mW to 400 mW and modulated pulse trains of different duration and period were experimented. Different treatment parameters achieved different degrees of spatial confinement of tissue alterations as visualized by 3-D RCM/TPF/SHG imaging. At 200 mW power level, 0.1 s pulse train duration, 4.1 s pulse train period, the tissue damage was found to be restricted precisely to the 50µm×50µm×10µm volume, where the laser focus spot had scanned through. The overlying epidermis/dermis tissue and the underneath dermis tissue were intact although there was light passing through these regions.

Keywords: multiphoton absorption photothermolysis, reflectance confocal microscopy, second harmonic generation microscopy, spatially selective photothermolysis, two-photon fluorescence microscopy

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104 Prevalence and Predictors of Metabolic Syndrome among Diabetic Clinic Attendees in Sokoto, Nigeria

Authors: Kehinde Joseph Awosan, Balarabe Adami Isah, Edzu Usman Yunusa, Sarafadeen Adeniyi Arisegi, Izuchukwu Obasi, Oluchi Solomon-Anucha

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Background: Metabolic syndrome (MetS) is prevalent in patients with diabetes mellitus and a significant risk for major cardiovascular events. Identifying its burden and peculiarities is crucial to preventing complications among those at risk. Aim: This study was conducted to determine the prevalence and predictors of metabolic syndrome among diabetes clinic attendees in Sokoto, Nigeria. Materials and Methods: A cross-sectional study was conducted among 365 patients with type 2 diabetes attending the diabetes clinic of Specialist Hospital, Sokoto, Nigeria. A structured questionnaire was used to obtain data on the respondents’ socio-demographic variables, treatment history, and lifestyle. Blood pressure and anthropometric measurements (including weight, height, and waist circumference) were done for the patients. Likewise, biochemical assessment (including fasting plasma glucose, high-density lipoprotein cholesterol (HDL-c), and triglyceride (TG) was done. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Data were analyzed using the IBM Statistical Package for Social Sciences (SPSS) version 25. Results: The ages of the patients ranged from 30 to 78 (mean = 50.9 ±11.7) years. The overall prevalence of MetS was 57.3%, with a higher prevalence in females (68.1%) than males (43.0%). The most common components of MetS observed were hypertension (69.2%), and elevated fasting plasma glucose (65.7%); while the predictors of MetS were age > 50 years (OR 6.960, 95% CI: 3.836-12.628, p < 0.001), female sex (OR 2.300, 95% CI: 1.355-3.903, p = 0.002), physical activity (OR 0.214, 95% CI: 0.126-0.363, p < 0.001), and overweight/obesity (OR 3.356, 95% CI: 1.838-6.127, p < 0.001). Conclusion: Metabolic syndrome is prevalent among patients with type 2 diabetes in Sokoto, Nigeria, and the predictors were age > 50 years, female sex, physical activity, and overweight/obesity. Diabetes care providers should screen their patients for MetS to prevent adverse cardiovascular events.

Keywords: prevalence, predictors, metabolic syndrome, diabetes

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103 Nutrigenetic and Bioinformatic Analysis of Rice Bran Bioactives for the Treatment of Lifestyle Related Disease Diabetes and Hypertension

Authors: Md. Alauddin, Md. Ruhul Amin, Md. Omar Faruque, Muhammad Ali Siddiquee, Zakir Hossain Howlader, Mohammad Asaduzzaman

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Diabetes and hypertension are the major lifestyle related diseases. The α-amylase and angiotensin converting enzymes (ACE) are the key enzymes that regulate diabetes and hypertension. The aim was to develop a drug for the treatment of diabetes and hypertension. The Rice Bran (RB) sample (Oryza sativa; BRRI-Dhan-84) was collected from the Bangladesh Rice Research Institute (BRRI), and rice bran proteins were isolated and hydrolyzed by hydrolyzing enzyme alcalase and trypsin. In vivo experiment suggested that rice bran bioactives has an effect on regulating the expression of several key gluconeogenesis and lipogenesis-regulating genes, such as glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, and fatty acid synthase. The above genes have a connection of regulating the glucose level, lipids profile as well as act as an anti-inflammatory agent. A molecular docking, bioinformatics and in vitro experiments were performed. We found rice bran protein hydrolysates significantly (<0.05) influence the peptide concentration in the case of trypsin, alcalase, and (trypsin + alcalase) digestion. The in vitro analysis found that protein hydrolysate significantly (<0.05) reduced diabetic and hypertension as well as oxidative stress. A molecular docking study showed that the YY and IP peptide have a significantly strong binding affinity to the active site of the ACE enzyme and α-amylase with -7.8Kcal/mol and -6.2Kcal/mol, respectively. The Molecular dynamics (MD) simulation and Swiss ADME data analysis showed that less toxicity risk, good physicochemical properties, pharmacokinetics, and drug-likeness with drug scores 0.45 and 0.55 of YY and IP peptides, respectively. Thus, rice bran bioactive could be a good candidate for the treatment of diabetes and hypertension.

Keywords: anti-hypertensive and anti-hyperglycemic, anti-oxidative, bioinformatics, in vitro study, rice bran proteins and peptides

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102 Prevalence and Drug Susceptibility Profiles of Bacterial Urinary Tract Infections Isolated among Diabetes Mellitus Patients at Bosaso Health Centers

Authors: Said Abdirasak Abidrahman, Ibrahim Mohamed

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Background: Urinary Tract Infections (UTIs) are the commonest infections described among diabetes mellitus patients. More often, empirical antimicrobial therapy is initiated before the laboratory results are made available with minimal treatment success. The knowledge of the etiology and antibiotic susceptibility patterns of the organisms causing urinary tract infections among diabetes mellitus patients remains scarce, despite its vitality. This study sought to determine the prevalence, bacteria species, and drug susceptibility patterns of common causes of urinary tract infections among diabetes mellitus patients attending Bosaso health centers. Materials and methods: We conducted a cross-sectional study involving adult diabetic patients at Bosaso health centers between the months of May and July 2020. Laboratory assay of mid-stream urine samples was done to isolate bacteria causes of UTIs. These were biochemically identified using Gram stain, Kligler iron agar (KIA), Indole test, citrate, urea, coagulase, catalase, motility agar, and lysine iron agar. Their antibiotic susceptibility pattern for the isolated organisms was made for Ampicillin 10μg, Ciprofloxacin 5μg, Cotrimoxazole 25μg, Gentamycin 10μg, Ceftriaxone 10μg, and determined using the Kirby Bauer Disc Diffusion method. Results: Of 177 participants, 69 (39.0%) were males and 108 (61.0%) were females. Their mean age was 33.1 years (range; 18-67 years). Of these, 14.7% (26/177) of the samples revealed significant growth (>= 105 CFU/mL) giving a prevalence of 14.9 % (95% CI: 10.6 to 16.3). The organisms isolated were Escherichia coli -50% (N=13), Klebsiella pneumonia 30.8% (N=8), Staphylococcus aureus 15.4% (N=4), and unidentified organism 3.8% (N=1), and these were associated with such socio-demographic factors like history of catheterization and sexual activity. Antibiotic susceptibility to the commonly used agents for treating UTIs indicated higher sensitivity to Gentamicin and Ceftriaxone.

Keywords: antimicrobials, bacteria, urinary tract infections, diabetes

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101 In vitro α-Amylase and α-Glucosidase Inhibitory Activities of Bitter Melon (Momordica charantia) with Different Stage of Maturity

Authors: P. S. Percin, O. Inanli, S. Karakaya

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Bitter melon (Momordica charantia) is a medicinal vegetable, which is used traditionally to remedy diabetes. Bitter melon contains several classes of primary and secondary metabolites. In traditional Turkish medicine bitter melon is used for wound healing and treatment of peptic ulcers. Nowadays, bitter melon is used for the treatment of diabetes and ulcerative colitis in many countries. The main constituents of bitter melon, which are responsible for the anti-diabetic effects, are triterpene, protein, steroid, alkaloid and phenolic compounds. In this study total phenolics, total carotenoids and β-carotene contents of mature and immature bitter melons were determined. In addition, in vitro α-amylase and α-glucosidase activities of mature and immature bitter melons were studied. Total phenolic contents of immature and mature bitter melon were 74 and 123 mg CE/g bitter melon respectively. Although total phenolics of mature bitter melon was higher than that of immature bitter melon, this difference was not found statistically significant (p > 0.05). Carotenoids, a diverse group of more than 600 naturally occurring red, orange and yellow pigments, play important roles in many physiological processes both in plants and humans. The total carotenoid content of mature bitter melon was 4.36 fold higher than the total carotenoid content of immature bitter melon. The compounds that have hypoglycaemic effect of bitter melon are steroidal saponins known as charantin, insulin-like peptides and alkaloids. α-Amylase is one of the main enzymes in human that is responsible for the breakdown of starch to more simple sugars. Therefore, the inhibitors of this enzyme can delay the carbohydrate digestion and reduce the rate of glucose absorption. The immature bitter melon extract showed α-amylase and α-glucosidase inhibitory activities in vitro. α-Amylase inhibitory activity was higher than that of α-glucosidase inhibitory activity when IC50 values were compared. In conclusion, the present results provide evidence that aqueous extract of bitter melon may have an inhibitory effect on carbohydrate breakdown enzymes.

Keywords: bitter melon, in vitro antidiabetic activity, total carotenoids, total phenols

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100 Methylglyoxal Induced Glycoxidation of Human Low Density Lipoprotein: A Biophysical Perspective and Its Role in Diabetes and Periodontitis

Authors: Minhal Abidi, Moinuddin

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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.

Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis

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99 Genetically Modified Organisms

Authors: Mudrika Singhal

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The research paper is basically about how the genetically modified organisms evolved and their significance in today’s world. It also highlights about the various pros and cons of the genetically modified organisms and the progress of India in this field. A genetically modified organism is the one whose genetic material has been altered using genetic engineering techniques. They have a wide range of uses such as transgenic plants, genetically modified mammals such as mouse and also in insects and aquatic life. Their use is rooted back to the time around 12,000 B.C. when humans domesticated plants and animals. At that humans used genetically modified organisms produced by the procedure of selective breeding and not by genetic engineering techniques. Selective breeding is the procedure in which selective traits are bred in plants and animals and then are domesticated. Domestication of wild plants into a suitable cultigen is a well known example of this technique. GMOs have uses in varied fields ranging from biological and medical research, production of pharmaceutical drugs to agricultural fields. The first organisms to be genetically modified were the microbes because of their simpler genetics. At present the genetically modified protein insulin is used to treat diabetes. In the case of plants transgenic plants, genetically modified crops and cisgenic plants are the examples of genetic modification. In the case of mammals, transgenic animals such as mice, rats etc. serve various purposes such as researching human diseases, improvement in animal health etc. Now coming upon the pros and cons related to the genetically modified organisms, pros include crops with higher yield, less growth time and more predictable in comparison to traditional breeding. Cons include that they are dangerous to mammals such as rats, these products contain protein which would trigger allergic reactions. In India presently, group of GMOs include GM microorganisms, transgenic crops and animals. There are varied applications in the field of healthcare and agriculture. In the nutshell, the research paper is about the progress in the field of genetic modification, taking along the effects in today’s world.

Keywords: applications, mammals, transgenic, engineering and technology

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98 Effect of 16 Weeks Walking with Different Dosages on Psychosocial Function Related Quality of Life among 60 to 75 Years Old Men

Authors: Mohammad Ehsani, Elham Karimi, Hashem Koozechian

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Aim: The purpose of current semi-experimental study was a survey on effect of 16 week walking on psychosocial function related quality of life among 60 to 75 years old men. Methodology: For this reason, short from of health – related quality of life questionnaire (SF – 36) and Geriatric Depression Scale (GDS) had been distributed to the subjects at 2 times of pre – test and posttest. Statistical sample of current study was 60 to 75 years old men who placed at Kahrizak house and assessed by considering physically and medical background. Also factors of entrance to the intervention like age range, have satisfaction and have intent to participating in walking program, lack of having diabetic, cardiovascular, Parkinsonism diseases and postural, neurological, musculoskeletal disorders, lack of having clinical background like visual disorders or disordering on equilibrium system, lack of motor limitation, foot print disorders, having surgery and mental health had been determined and assessed. Finally after primary studies, 80 persons selected and categorized accidentally to the 3 experimental group (1, 2, 3 sessions per week, 30 min walking with moderate intension at every sessions) and one control group (without physical activity in period of 16 weeks). Data analysed by employing ANOVA, Pearson coefficient and Scheffe Post – Hoc tests at the significance level of p < 0.05. Results: Results showed that psychosocial function of men with 60 to 75 years old increase by influence of 16 week walking and increase of exercise sessions lead to more effectiveness of walking. Also there was no significant difference between psychosocial function of subjects within 1 session and 3 sessions experimental groups (p > 0.05). Conclusion: On the basis of results, we can say that doing regular walking with efficient and standard dosage for elderly people, can increase their quality of life. Furthermore, designing and action operation regular walking program for elderly men on the basis of special, logical and systematic pattern under the supervision of aware coaches have been recommended on the basis of results.

Keywords: walking, quality of life, psychosocial function, elders

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97 Nanoparticles of Hyaluronic Acid for Radiation Induced Lung Damages

Authors: Anna Lierova, Jitka Kasparova, Marcela Jelicova, Lucie Korecka, Zuzana Bilkova, Zuzana Sinkorova

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Hyaluronic acid (HA) is a simple linear, unbranched polysaccharide with a lot of exceptional physiological and chemical properties such as high biocompatibility and biodegradability, strong hydration and viscoelasticity that depend on the size of the molecule. It plays the important role in a variety of molecular events as tissue hydration, mechanical protection of tissues and as well as during inflammation, leukocyte migration, and extracellular matrix remodeling. Also, HA-based biomaterials, including HA scaffolds, hydrogels, thin membranes, matrix grafts or nanoparticles are widely use in various biomedical applications. Our goal is to determine the radioprotective effect of hyaluronic acid nanoparticles (HA NPs). We are investigating effect of ionizing radiation on stability of HA NPs, in vitro relative toxicity of nanoscale as well as effect on cell lines and specific surface receptors and their response to ionizing radiation. An exposure to ionizing radiation (IR) can irreversibly damage various cell types and may thus have implications for the level of the whole tissue. Characteristic manifestations are formation of over-granulated tissue, remodeling of extracellular matrix (ECM) and abortive wound healing. Damages are caused by either direct interaction with DNA and IR proteins or indirectly by radicals formed during radiolysis of water Accumulation and turnover of ECM are a hallmark of radiation induces lung injury, characterized by inflammation, repair or remodeling health pulmonary tissue. HA is a major component of ECM in lung and plays an important role in regulating tissue injury, accelerating tissue repair, and controlling disease outcomes. Due to that, HA NPs were applied to in vivo model (C57Bl/6J mice) before total body or partial thorax irradiation. This part of our research is targeting on effect of exogenous HA on the development and/or mitigating acute radiation syndrome and radiation induced lung injuries.

Keywords: hyaluronic acid, ionizing radiation, nanoparticles, radiation induces lung damages

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96 Kidney Stones in Individuals Living with Diabetes Mellitus at King Abdul-Aziz Medical City - Tertiary Care Center, Jeddah, Saudi Arabia: A Retrospective Cohort Study

Authors: Suhaib Radi, Ibrahim Basem Nafadi, Abdullah Ahmed Alsulami, Nawaf Faisal Halabi, Abdulrhman Abdullah Alsubhi, Sami Wesam Maghrabi, Waleed Saad Alshehri

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Background: Kidney stones greatly affect individuals. The range of these effects regarding multiple kidney stone factors (size, presence of obstruction, and modality of treatment) in stone formers with and without diabetes has not been well explored in the literature to the best of the author's knowledge. Our goal is to investigate this unexplored correlation between diabetes and kidney stones by conducting a Cohort retrospective study to precisely evaluate the effects of this condition and the existence of complications in adult individuals with diabetes in Saudi Arabia in comparison to a non-diabetic control group. Methodology: This is a retrospective cohort study aiming to evaluate the range of effects of kidney stones in stone formers in a group of adults diagnosed with type 2 diabetes mellitus and adults without diabetes between 2017 and 2019 in Jeddah, Saudi Arabia. An IRB approval has been granted for this study. The data was analyzed using SPSS. The data was collected from the 1st of December 2022 until the 1st of March 2023. Results: A total of 254 individuals diagnosed with kidney stones were included, 127 of whom were adult individuals with type 2 diabetes, and 127 were non-diabetics. Our study shows that the individuals affected with diabetes were more likely to have larger kidney stones in comparison to individuals without diabetes (13.12 mm vs. 10.53 mm, p-value = 0.03). Moreover, individuals with hypertension and dyslipidemia also had significantly larger stones. On the other hand, no significant difference was found in the presence of obstruction and modality of treatment between the two groups. Conclusion: This study done in Saudi Arabia found that individuals with kidney stones who concurrently had diabetes formed larger kidney stones, and they were also found to have other comorbidities such as HTN, dyslipidemia, obesity, and renal disease. The significance of these findings could assist in the future of primary and secondary prevention of renal stones.

Keywords: kidney stone, type 2 DM, metabolic syndrome, lithotripsy

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95 Evaluation of Important Transcription Factors and Kinases in Regulating the Signaling Pathways of Cancer Stem Cells With Low and High Proliferation Rate Derived From Colorectal Cancer

Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini

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Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.

Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells

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94 Neuroprotective Effect of Vildagliptin against Cerebral Ischemia in Rats

Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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93 Tourism Development and Planning in Rwanda

Authors: Ntachobazi bosco

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Tourism Development and Planning in Rwanda: Rwanda, a small landlocked country located in the heart of Africa, has experienced significant growth in its tourism industry in recent years. The country’s stunning natural beauty, rich cultural heritage, and warm hospitality have made it an attractive destination for travelers from around the world. However, to ensure sustainable tourism development and planning, the Rwandan government has implemented various strategies and policies to promote responsible tourism practices. Infrastructure Development: To support the growth of the tourism industry, the Rwandan government has invested heavily in infrastructure development. This includes the construction of new hotels, resorts, and lodges, as well as the upgrading of existing facilities. The government has also improved the country’s transportation network, including the construction of new airports and the upgrading of existing ones. Conservation Efforts: Rwanda is home to several national parks and reserves, including the famous Volcanoes National Park, which is known for its mountain gorilla populations. To protect these natural wonders, the Rwandan government has implemented conservation efforts, such as the establishment of protected areas and the development of sustainable tourism practices. Community-Based Tourism: Community-based tourism is a key component of Rwanda’s tourism development strategy. The government has established several community-based tourism programs, which aim to involve local communities in the tourism industry and provide them with economic benefits. These programs include homestays, village tours, and cultural performances. Sustainable Tourism Practices: To promote sustainable tourism practices, the Rwandan government has implemented several initiatives, such as the use of eco-friendly accommodations and the promotion of responsible wildlife viewing practices. The government has also established the Rwanda Tourism Board, which is responsible for promoting and regulating the tourism industry. Challenges and Opportunities: Despite the growth of the tourism industry in Rwanda, several challenges need to be addressed, such as the lack of skilled labor and the need for more infrastructure development. However, there are also several opportunities for the industry, such as the potential for ecotourism and the growth of the meetings, incentives, conventions, and exhibitions (MICE) market.

Keywords: tourism, in rwanda, developent, in africa

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92 The Effects of Ultrasound on the Extraction of Ficus deltoidea Leaves

Authors: Nur Aimi Syairah Mohd Abdul Alim, Azilah Ajit, A. Z. Sulaiman

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The present study aimed to investigate the effects of ultrasound-assisted extraction (UAE) on the extraction of Vitexin and Iso-Vitexin from Ficus deltoidea plants. In recent years, ultrasound technology has been found to be a potential herbal extraction technique. The passage of ultrasound energy in a liquid medium generates mechanical agitation and other physical effects due to acoustic cavitation. The main goal is to optimised ultrasonic-assisted extraction condition providing the highest extraction yield with the most desirable antioxidant activity and stability. Thus, a series of experiments has been developed to investigate the effect of ultrasound energy on the vegetal material and the implemented parameters by using HPLC-photodiode array detection. The influences of several experimental parameters on the ultrasonic extraction of Ficus deltoidea leaves were investigated: extraction time (1-8 h), solvent-to-water ratio (1:10 to 1:50), temperature (50–100 °C), duty cycle (10–continuous sonication) and intensity. The extracts at the optimized condition were compared with those obtained by conventional boiling extraction, in terms of bioactive constituents yield and chemical composition. The compounds of interest identified in the extracts were Vitexin and Isovitexin, which possess anti-diabetic, anti-oxidant and anti-cancer properties. Results showed that the main variables affecting the extraction process were temperature and time. Though in less extent, solvent-to-water ratio, duty cycle and intensity are also demonstrated to be important parameters. The experimental values under optimal conditions were in good consistent with the predicted values, which suggested that ultrasonic-assisted extraction (UAE) is more efficient process as compared to conventional boiling extraction. It recommended that ultrasound extraction of Ficus deltoidea plants are feasible to replace the traditional time-consuming and low efficiency preparation procedure in the future modernized and commercialized manufacture of this highly valuable herbal medicine.

Keywords: Ficus, ultrasounds, vitexin, isovitexin

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91 An Inquiry on Imaging of Soft Tissues in Micro-Computed Tomography

Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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90 Alteration of Placental Development and Vascular Dysfunction in Gestational Diabetes Mellitus Has Impact on Maternal and Infant Health

Authors: Sadia Munir

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The aim of this study is to investigate changes in placental development and vascular dysfunction which subsequently affect feto-maternal health in pregnancies complicated by gestational diabetes mellitus (GDM). Fetal and postnatal adverse health outcomes of GDM are shown to be associated with disturbances in placental structure and function. Children of women with GDM are more likely to be obese and diabetic in childhood and adulthood. GDM also increases the risk of adverse pregnancy outcomes, including preeclampsia, birth injuries, macrosomia and neonatal hypoglycemia, respiratory distress syndrome, neonatal cardiac dysfunction and stillbirth. Incidences of type 2 diabetes in the MENA region are growing at an alarming rate which is estimated to become more than double by 2030. Five of the top 10 countries for diabetes prevalence in 2010 were in the Gulf region. GDM also increases the risk of development of type 2 diabetes. Interestingly, more than half of the women with GDM develop diabetes later in their life. The human placenta is a temporary organ located at the interface between mother and fetal blood circulation. Placenta has a central role as both a producer as well as a target of several molecules that are involved in placental development and function. We have investigated performed a Pubmed search with key words placenta, GDM, placental villi, vascularization, cytokines, growth factors, inflammation, hypoxia, oxidative stress and pathophysiology. We have investigated differences in the development and vascularization of placenta, their underlying causes and impact on feto-maternal health through literature review. We have also identified gaps in the literature and research questions that need to be answered to completely understand the central role of placenta in the GDM. This study is important in understanding the pathophysiology of placenta due to changes in the vascularization of villi, surface area and diameter of villous capillaries in pregnancies complicated by GDM. It is necessary to understand these mechanisms in order to develop treatments to reverse their effects on placental malfunctioning, which in turn, will result in improved mother and child health.

Keywords: gestational diabetes mellitus, placenta, vasculature, villi

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89 Prevalence and Correlates of Complementary and Alternative Medicine Use among Diabetic Patients in Lebanon: A Cross-Sectional Study

Authors: Farah Naja, Mohamad Alameddine

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Background: The difficulty of compliance to therapeutic and lifestyle management of type 2 diabetes mellitus (T2DM) encourages patients to use complementary and alternative medicine (CAM) therapies. Little is known about the prevalence and mode of CAM use among diabetics in the Eastern Mediterranean Region in general and Lebanon in particular. Objective: To assess the prevalence and modes of CAM use among patients with T2DM residing in Beirut, Lebanon. Methods: A cross-sectional survey of T2DM patients was conducted on patients recruited from two major referral centers - a public hospital and a private academic medical center in Beirut. In a face-to-face interview, participants completed a survey questionnaire comprised of three sections: socio-demographic, diabetes characteristics and types and modes of CAM use. Descriptive statistics, univariate and multivariate logistic regression analyses were utilized to assess the prevalence, mode and correlates of CAM use in the study population. The main outcome in this study (CAM use) was defined as using CAM at least once since diagnosis with T2DM. Results: A total of 333 T2DM patients completed the survey (response rate: 94.6%). Prevalence of CAM use in the study population was 38%, 95% CI (33.1-43.5). After adjustment, CAM use was significantly associated with a “married” status, a longer duration of T2DM, the presence of disease complications, and a positive family history of the disease. Folk foods and herbs were the most commonly used CAM followed by natural health products. One in five patients used CAM as an alternative to conventional treatment. Only 7 % of CAM users disclosed the CAM use to their treating physician. Health care practitioners were the least cited (7%) as influencing the choice of CAM among users. Conclusion: The use of CAM therapies among T2DM patients in Lebanon is prevalent. Decision makers and care providers must fully understand the potential risks and benefits of CAM therapies to appropriately advise their patients. Attention must be dedicated to educating T2DM patients on the importance of disclosing CAM use to their physicians especially patients with a family history of diabetes, and those using conventional therapy for a long time.

Keywords: nutritional supplements, type 2 diabetes mellitus, complementary and alternative medicine (CAM), conventional therapy

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