Search results for: candidate gene of type-2 diabetes

Authors: Yu-Chen Hu

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Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: Dedy Pratama, Akhmadu Muradi, Hilman Ibrahim, Raden Suhartono, Alexander Jayadi Utama, Patrianef Darwis, S. Dwi Anita, Luluk Yunaini, Kemas Dahlan

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Introduction: Vascular endothelial growth factor (VEGF) gene shows association with various angiogenesis conditions including Diabetic Foot Ulcer (DFU) disease. In this study, we performed this study to examine VEGF gene polymorphism associated with DFU. Methods: Case-control study of polymorphism of VEGF gene +405 C>G and -460 T>C, of diabetes mellitus (DM) type 2 with Diabetic Foot Ulcer (DFU) in Cipto Mangunkusumo National Hospital (RSCM) Jakarta from June to December 2016. Results: There were 203 patients, 102 patients with DFU and 101 patients without DFU. Forty-nine point 8 percent of total samples is male and 50,2% female with mean age 56,06 years. Distribution of the wild-type genotype VEGF +405 C>G wild type CC was found in 6,9% of respondents, the number of mutant heterozygote CG was 69,5% and mutant homozygote GG was 19,7%. Cumulatively, there were 6,9% wild-type and 85,2% mutant and 3,9% of total blood samples could not be detected on PCR-RFLP. Distribution of VEGF allele +405 C>G C alleles were 43% and G alleles were 57%. Distribution of genotype from VEGF gene -460 T>C is wild type TT 42,9%, mutant heterozygote TC 37,9% and mutant homozygote CC 13,3%. Cumulatively, there were 42,9% wild-type and 51% mutant type. Distribution of VEGF -460 T>C were 62% T allele and 38% C allele. Conclusion: In this study we found the distribution of alleles from VEGF +405 C>G is C 43% and G 57% and from VEGF -460 T>C; T 62% and C 38%. We propose that G allele in VEGF +405 C>G can act as a protective allele and on the other hands T allele in VEGF -460 T>C could be acted as a risk factor for DFU in diabetic patients.

Keywords: diabetic foot ulcer, diabetes mellitus, polymorphism, VEGF

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Authors: Amani Ashari, Julia Omar, Arif Hashim, Shahrul Hamid

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Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The APOE ɛ3 allele was the most common one in both groups. There was no significant association between the APOE genotypes and the CAD status in Type 2 DM using Pearson χ² test. Further analysis indicated there were no significant differences in all lipid parameters between E2, E3 and E4 subgroups in both groups. The study showed that the E4 allele carriers of Type 2 DM with CAD patients had higher LDL-C level and lower HDL-C level compared to the other allele carriers. However, analyses showed these levels were not statistically different. The study also showed that the Type 2 DM with CAD group with E2 allele had higher triglyceride (TG). In conclusion, further study with larger sample size is needed to confirm role of E4 as a marker of CAD among Type 2 DM patients in Malaysian population.

Keywords: Apolipoprotein E, diabetes mellitus, cardiovascular disease, lipids

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Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

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Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Diana Gibson

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Aim: The first aim of the study was to ascertain the percentage of people who had been diagnosed with High Blood Pressure and/ or Type2 Diabetes Mellitus in Matzikama municipal district, Western Cape, South Africa. These two conditions are reportedly very high in this particular province, even though few statistics are available. A second aim was to gain insight into the understanding of these two conditions among sufferers. A third aim was to determine their allopathic use as well as indigenous medicinal plants to manage these conditions. A fourth aim was to understand how users of medicinal plants attend to their materiality and relationality as a continuum between humans and plants. The final aim was to ascertain the conservation status of medicinal plants utilised. Methods: One thousand one hundred and eighty-four (1184) respondents were interviewed. Semi-structured surveys were utilised to gather data on the percentage of people who had been medically diagnosed with High Blood Pressure and/or Type 2 Diabetes Mellitus. Local healers and knowledgeable old people were subsequently selected through a non-probability snowball sampling method. They were helped with plant collection. The plants were botanically identified. Results: The study found that people who have been diagnosed with High Blood Pressure or Type 2 Diabetes Mellitus drew on and continuously moved between biomedical and local understandings of these conditions. While they followed biomedical treatment regimens as far as possible they also drew on alternative ways of managing it through the use of medicinal plants. The most commonly used plant species overall were Lessertia frutescens, Tulbaghia violacea, Artemisia afra and Leonotus leonurus. For the users, medicinal plants were not mere material entities, they were actants in social networks where knowledge was produced through particular practices in specific places. None of the identified plants are currently threatened. Significance: Sufferers had a good understanding of the symptoms of and biomedical treatment regime for both conditions, but in everyday life they adhered to their local understandings and medicinal plants for treatment. The majority used reportedly used prescribed medication as well as plant alternatives.

Keywords: diabetes, high blood pressure, medicine, plants

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Authors: Narendra Kumar

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In developing countries, the majority of people with diabetes are in the age range of 45-64 years and more women than men. As in many areas of the India, non-insulin dependent diabetes mellitus has become major problems. Now it is spreading among the middle class and poor at an alarming stage in India and Kerala is turning to be the world capital of diabetes. This study uses two round NSS data from the ‘National Sample Survey Organization, India’ to investigate the predictors of diabetes in Kerala. The overall estimates for diabetes prevalence among elderly show that higher in men than women, but there are more women with diabetes than men. Education of respondent has been found a significant characteristics, further respondent working status, caste/tribe have substantial impact on diabetes in Kerala. The disease is more common for people who are mostly physically inactive. This whole picture is very much prominent in the urban areas compared with the rural ones. Not working elderly have significantly higher with diabetes than for those working in elderly. Socioeconomic status was inversely associated with diabetes prevalence. For men and women, the prevalence of diabetes and hypertension were significantly higher in the urban population while smoking, smokeless tobacco consumption was more prevalent in the rural population. High alcohol intake increases diabetes risk among elderly. Finally these findings specified that an increase improve health care services and changing life style of elderly which should in turn raise diabetes patient survival and should decrease comorbidities due to diabetes in Kerala.

Keywords: elderly, diabetes, prevalence, Kerala

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Authors: Fadhl Alakwaa

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One of the sustainable goals of the system biology is understanding gene-gene interactions. Hence, gene regulatory networks (GRN) need to be constructed for understanding the disease ontology and to reduce the cost of drug development. To construct gene regulatory from gene expression we need to overcome many challenges such as data denoising and dimensionality. In this paper, we develop an integrated system to reduce data dimension and remove the noise. The generated network from our system was validated via available interaction databases and was compared to previous methods. The result revealed the performance of our proposed method.

Keywords: gene regulatory network, biclustering, denoising, system biology

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Authors: Mahmoud M. Zakaria, Omnia F. Elmoursi, Mahmoud M. Gabr, Camelia A. AbdelMalak, Mohamed A. Ghoneim

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Many protocols were publicized for differentiation of human mesenchymal stem cells (MSCS) into insulin-producing cells (IPCs) in order to excrete insulin hormone ingoing to treat diabetes disease. Our aim is to evaluate relative gene expression for each independent protocol. Human bone marrow cells were derived from three volunteers that suffer diabetes disease. After expansion of mesenchymal stem cells, differentiation of these cells was done by three different protocols (the one-step protocol was used conophylline protein, the two steps protocol was depending on trichostatin-A, and the three-step protocol was started by beta-mercaptoethanol). Evaluation of gene expression was carried out by real-time PCR: Pancreatic endocrine genes, transcription factors, glucose transporter, precursor markers, pancreatic enzymes, proteolytic cleavage, extracellular matrix and cell surface protein. Quantitation of insulin secretion was detected by immunofluorescence technique in 24-well plate. Most of the genes studied were up-regulated in the in vitro differentiated cells, and also insulin production was observed in the three independent protocols. There were some slight increases in expression of endocrine mRNA of two-step protocol and its insulin production. So, the two-step protocol was showed a more efficient in expressing of pancreatic endocrine genes and its insulin production than the other two protocols.

Keywords: mesenchymal stem cells, insulin producing cells, conophylline protein, trichostatin-A, beta-mercaptoethanol, gene expression, immunofluorescence technique

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Authors: Leila Yazdanpanah, Hajieh Shahbazian, Seyed Mahmoud Latifi, Armaghan Moravej Aleali, Saeed Ghanbari

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Introduction: This study was designed to determine the prevalence of diabetes in people aged over 20 years in Ahvaz, Iran. Material and Methods: The study population selected by cluster sampling. Fasting blood sugar (FBS) assessed after minimum 8 hours night fasting. A questionnaire included: age, sex, weight, height, blood pressure, waist circumference and previous history of diabetes were completed for each patient. FBS≥126mg/dl and/or oral hypoglycemic treatment and/or insulin was defined as diabetes, FBS=100-125 mg/dl as impaired fasting glucose (IFG) and FBS<100mg/dl as normal. Results: Study population was 936 persons (47.2 % male and 52.8% female). The mean age of a population was 42.2±14 years. Diabetes was detected in 15.1 % of population. Only 57cases(6.1%) were aware of their disease and 9% had unknown diabetes. Diabetes was detected in 14.5% of male (11.3% unknown and 3.2 % known diabetes) and in 11.7% of female (7% unknown and 4.7% known diabetes). Prevalence of diabetes had no significant difference (P=0.21) in male and female but unknown diabetes was significantly higher in male (P=0.025). Prevalence of diabetes was increased with rising of age between 20-60 years old but decreasing after 60 years old. Diabetes was related to age, waist circumference and systolic and diastolic blood pressure, TG level and BMI in both sex (P=0.0001). Conclusion: More than half of female and three-fourth of male diabetic patients are unaware of their disease in South of Iran. Diabetes screening should be intensified in this population.

Keywords: diabetes, prevalence, risk factor, awareness

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Authors: Reham Algheshairy

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The purpose of this research study is to identify the beneficial effects of Nigella sativa seeds, cherries and Ajwah dates on blood glucose levels among people with type 2 diabetes in the KSA population and healthy people in the UK. My hypothesis questions whether or not people with type 2 diabetes can lead a healthier life using these dietary supplements.

Keywords: diabetes type 2, cherry, nigella seeds, Ajwa date

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Authors: Restu Misrianti

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The amino acid variation of Asn (allele A) at position 631 in Mx gene was specific to positive antiviral to avian viral desease. This research was aimed at identifying polymorphism of Mx gene in duck using molecular technique. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique was used to select the genotype of AA, AG and GG. There were thirteen duck from Indragiri Hulu regency (Riau Province) used in this experiment. DNA amplification results showed that the Mx gene in duck is found in a 73 bp fragment. Mx gene in duck did not show any polymorphism. The frequency of the resistant allele (AA) was 0%, while the frequency of the susceptible allele (GG) was 100%.

Keywords: duck, Mx gene, PCR, RFLP

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Authors: Ng Liang Shen, Ngahzaifa Abdul Ghani

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This research aimed at developing an early warning system for pre-diabetic and diabetics by analyzing simple and easily determinable signs and symptoms of diabetes among the people living in Malaysia using Particle Swarm Optimized Artificial. With the skyrocketing prevalence of Type 2 diabetes in Malaysia, the system can be used to encourage affected people to seek further medical attention to prevent the onset of diabetes or start managing it early enough to avoid the associated complications. The study sought to find out the best predictive variables of Type 2 Diabetes Mellitus, developed a system to diagnose diabetes from the variables using Artificial Neural Networks and tested the system on accuracy to find out the patent generated from diabetes diagnosis result in machine learning algorithms even at primary or advanced stages.

Keywords: diabetes diagnosis, Artificial Neural Networks, artificial intelligence, soft computing, medical diagnosis

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Authors: Nandhana Vivek, Bhaskar Gogoi, Ayyavu Mahesh

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Breast cancer metastasis plays a key role in cancer progression and fatality. The present study examines the potential causes of metastasis in breast cancer by investigating the novel interactions between genes and their pathways. The gene expression profile of GSE99394, GSE1246464, and GSE103865 was downloaded from the GEO data repository to analyze the differentially expressed genes (DEGs). Protein-protein interactions, target factor interactions, pathways and gene relationships, and functional enrichment networks were investigated. The proliferation pathway was shown to be highly expressed in breast cancer progression and metastasis in all three datasets. Gene Ontology analysis revealed 11 DEGs as gene targets to control breast cancer metastasis: LYN, DLGAP5, CXCR4, CDC6, NANOG, IFI30, TXP2, AGTR1, MKI67, and FTH1. Upon studying the function, genomic and proteomic data, and pathway involvement of the target genes, DLGAP5 proved to be a promising candidate due to it being highly differentially expressed in all datasets. The study takes a unique perspective on the avenues through which DLGAP5 promotes metastasis. The current investigation helps pave the way in understanding the role DLGAP5 plays in metastasis, which leads to an increased incidence of death among breast cancer patients.

Keywords: genomics, metastasis, microarray, cancer

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Authors: Mahsa Taghavi

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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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Authors: Neelamshobha Nirala, R. Periyasamy, Awanish Kumar

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Diabetes is a metabolic disorder and with the increase of global prevalence of diabetes, cardiovascular diseases and mortality related to diabetes has also increased. Diabetes causes the increase of arterial stiffness by elusive hormonal and metabolic abnormalities. We used photoplethysmograph (PPG), a simple non-invasive method to study the change in arterial stiffness due to diabetes. Toe PPG signals were taken from 29 diabetic subjects with mean age of (65±8.4) years and 21 non-diabetic subjects of mean age of (49±14) years. Mean duration of diabetes is 12±8 years for diabetic group. Rise-time (RT) and area under rise time (AUR) were calculated from the PPG signal of each subject and Welch’s t-test is used to find the significant difference between two groups. We obtained a significant difference of (p-value) 0.0005 and 0.03 for RT and AUR respectively between diabetic and non-diabetic subjects. Average value of RT and AUR is 0.298±0.003 msec and 14.4±4.2 arbitrary units respectively for diabetic subject compared to 0.277±0.0005 msec and 13.66±2.3 a.u respectively for non-diabetic subjects. In conclusion, this study support that arterial stiffness is increased in diabetes and can be detected early using PPG.

Keywords: area under rise-time, AUR, arterial stiffness, diabetes, photoplethysmograph, PPG, rise-time (RT)

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Authors: Mohammad Hossain Validad, Maryam Nakhaei-Moghadam, Monire Mahjoob

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Introduction: The prevalence of type 1 diabetes is increasing worldwide, and given the role of ethnicity and race in complications of diabetes, this study was designed to evaluate the ocular complications of type 1 diabetes mellitus in Zahedan. Methods: This prospective cross-sectional study was conducted on Type 1 diabetic children that referred to Alzahra Eye Hospital. All patients had a dilated binocular indirect ophthalmoscopy using a +90 D condensing lens and slit-lamp biomicroscopy. Age, gender, onset, duration of diabetes, and HbA1c level were recorded. Results: 76 type 1 diabetes patients with an age of 11.93 ± 3.76 years participated in this study. Out of 76 patients with diabetes, 19 people (25%) had ocular complications. There was a significant difference in age (P=0.01) and disease duration (P=0.07) between the two groups with and without ocular complications. Odd ratios for ocular complications with age and duration of diabetes were 1.32 and 1.32, respectively. Conclusion: Cataract was the most common ocular complication in type 1 diabetes in Zahedan, a tropical region that was significantly related to the duration of the disease and the age of the patients.

Keywords: diabet mellitus type one, cataract, ocular complication, hemoglobin A1C

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Authors: Alyaa Abdlwahab

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Cutaneous leishmaniasis represents a serious health problem in Syria; this problem has become noticeably aggravated after the civil war in the country. Leishmania tropica parasite is the main cause of cutaneous leishmaniasis in Syria. In order to control the disease, we need an effective vaccine against leishmania parasite. DNA vaccination remains one of the favorable approaches that have been used to face cutaneous leishmaniasis. Ribosomal protein S4 is responsible for important roles in Leishmania parasite life. DNA vaccine based on S4 gene has been used against infections by many species of Leishmania parasite but leishmania tropica parasite, so this gene represents a good candidate for DNA vaccine construction. After proving the existence of ribosomal protein S4 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), sequencing it and cloning it into pCI plasmid, BALB/C mice were inoculated with pCI-S4 DNA vaccine. The immune response was determined by monitoring the lesion progression in inoculated BALB/C mice for six weeks after challenging mice with Leishmania tropica (LCED Syrian 01) parasites. IL-12, IFN-γ, and IL-4 were quantified in draining lymph nodes (DLNa) of the immunized BALB/C mice by using the RT-qPCR technique. The parasite burden was calculated in the final week for the footpad lesion and the DLNs of the mice. This study proved the existence and the expression of the ribosomal protein S4 gene in Leishmania tropica (LCED Syrian 01) promastigotes. The sequence of ribosomal protein cDNA S4 gene was determined and published in Genbank; the gene size was 822 bp. Expression was also demonstrated at the level of cDNA. Also, this study revealed that pCI-S4 DNA vaccine induces TH1\TH2 response in immunized mice; this response prevents partially developing a dermal lesion of Leishmania.

Keywords: ribosomal protein S4, DNA vaccine, Leishmania tropica, BALB\c

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Authors: Saeid Doaei

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The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of the existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In conclusion, the level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions.

Keywords: obesity, gene expression, FTO, macronutrients

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Authors: Samara R. Dania, Maulana S. Aji, Dewi Lestari

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Diabetes is a common disease in Indonesia. One of the risk factors of diabetes is an unhealthy diet which is consuming food that contains too much glucose, one of glucose sources presents in food containing carbohydrate. The purpose of this study is to identify the amount of glucose level in the consumed food. The authors use literature studies for this research method. For the results of this study, the authors expect diabetics to be more aware of diabetes by applying daily dietary regulation through D-Care. D-Care is an application that can enhance people awareness to diabetes in Indonesia. D-Care provides two menus; there are nutrition calculation and healthy food. Nutrition calculation menu is used for knowing estimated glucose intake level by calculating food that consumed each day. Whereas healthy food menu, it provides a combination of healthy food menu for diabetic. The conclusion is D-Care is useful to be used for reducing diabetes prevalence in Indonesia.

Keywords: D-Care, diabetes, awareness, healthy food

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Authors: Sadaf Ilyas

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Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.

Keywords: Interleukin 15, pET expression system, immune therapy, protein purification

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Authors: Mona Heydari, Ehsan Motamedian, Seyed Abbas Shojaosadati

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Prediction of perturbations after genetic manipulation (especially gene knockout) is one of the important challenges in systems biology. In this paper, a new algorithm is introduced that integrates microarray data into the metabolic model. The algorithm was used to study the change in the cell phenotype after knockout of Gss gene in Escherichia coli BW25113. Algorithm implementation indicated that gene deletion resulted in more activation of the metabolic network. Growth yield was more and less regulating gene were identified for mutant in comparison with the wild-type strain.

Keywords: metabolic network, gene knockout, flux balance analysis, microarray data, integration

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Authors: Nazanin Ahmadi Daryakenari

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Background: Diabetes significantly influences the risk of heart failure. The interplay between distinct types of diabetes, heart failure, and their distribution across various age groups remains an area of active exploration. This study endeavors to scrutinize the age group distribution in publications addressing Type 1 and Type 2 diabetes and heart failure on PubMed while also examining the evolving publication trends. Methods: We leveraged E-utilities and RegEx to search and extract publication data from PubMed using various mesh terms. Subsequently, we conducted descriptive statistics and t-tests to discern the differences between the two diabetes types and the distribution across age groups. Finally, we analyzed the temporal trends of publications concerning both types of diabetes and heart failure. Results: Our findings revealed a divergence in the age group distribution between Type 1 and Type 2 diabetes within heart failure publications. Publications discussing Type 2 diabetes and heart failure were more predominant among older age groups, whereas those addressing Type 1 diabetes and heart failure displayed a more balanced distribution across all age groups. The t-test revealed no significant difference in the means between the two diabetes types. However, the number of publications exploring the relationship between Type 2 diabetes and heart failure has seen a steady increase over time, suggesting an escalating interest in this area. Conclusion: The dissection of publication patterns on PubMed uncovers a pronounced association between Type 2 diabetes and heart failure within older age groups. This highlights the critical need to comprehend the distinct age group differences when examining diabetes and heart failure to inform and refine targeted prevention and treatment strategies.

Keywords: Type 1 diabetes, Type 2 diabetes, heart failure, age groups, publication patterns, PubMed

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Authors: K. S. Vimal, D. Bodhini, K. Ramya, N. Lakshmipriya, R. M. Anjana, V. Sudha, J. A. Lovegrove, V. Mohan, V. Radha

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Gene-lifestyle interaction studies have been carried out in various populations. However, to date there are no studies in an Asian Indian population. Hence, we examined whether lifestyle factors such as diet and physical activity modify the association between fat mass and obesity–associated (FTO) gene variants and obesity and type 2 diabetes (T2D) in an Asian Indian population. We studied 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the Chennai Urban Rural Epidemiology Study (CURES) in Southern India. Obesity was defined according to the World Health Organization Asia Pacific Guidelines (non-obese, BMI < 25 kg/m2; obese, BMI ≥ 25 kg/m2). Six single nucleotide polymorphisms (SNPs) in the FTO gene (rs9940128, rs7193144, rs8050136, rs918031, rs1588413 and rs11076023) identified from recent genome-wide association studies for T2D were genotyped by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Dietary assessment was carried out using a validated food frequency questionnaire and physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the model. A joint likelihood ratio test of the main SNP effects and the SNP-diet/physical activity interaction effects was used in the linear regression analyses to maximize statistical power. Statistical analyses were performed using STATA version 13. There was a significant interaction between FTO SNP rs8050136 and carbohydrate energy percentage (Pinteraction=0.04) on obesity, where the ‘A’ allele carriers of the SNP rs8050136 had 2.46 times higher risk of obesity than those with ‘CC’ genotype (P=3.0x10-5) among individuals in the highest tertile of carbohydrate energy percentage. Furthermore, among those who had lower levels of physical activity, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times higher risk of obesity than those with ‘CC’ genotype (P=4.0x10-5). We also found a borderline interaction between SNP rs11076023 and carbohydrate energy percentage (Pinteraction=0.08) on T2D, where the ‘A’ allele carriers in the highest tertile of carbohydrate energy percentage, had 1.57 times higher risk of T2D than those with ‘TT’ genotype (P=0.002). There was also a significant interaction between SNP rs11076023 and physical activity (Pinteraction=0.03) on T2D. No further significant interactions between SNPs and macronutrient intake or physical activity on obesity and T2D were observed. In conclusion, this is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. These findings suggest that the association between FTO gene variants and obesity and T2D is influenced by carbohydrate intake and physical activity levels. Greater understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions will advance the development of behavioral intervention and personalised lifestyle strategies predicted to reduce the development of metabolic diseases in ‘A’ allele carriers of both SNPs in this Asian Indian population.

Keywords: dietary intake, FTO, obesity, physical activity, type 2 diabetes, Asian Indian.

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Majed Ahmed Al-Mansoub, Muhammad Qamar

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There is a progressive increase in the prevalence of early onset Type 2 diabetes mellitus. Early detection of Type 2 diabetes enhances the length and/or quality of life which might result from a reduction in the severity, frequency or prevent or delay of its long-term complications. The study aims to determine the onset age for the first diagnosis of Type 2 diabetes mellitus. A retrospective study conducted in the endocrine clinic at Hospital Pulau Pinang in Penang, Malaysia, January- December 2016. Records of 519 patients with Type 2 diabetes mellitus were screened to collect demographic data and determine the age of first-time diabetes mellitus diagnosis. Patients classified according to the age of diagnosis, gender, and ethnicity. The study included 519 patients with age (55.6±13.7) years, female 265 (51.1%) and male 254 (48.9%). The ethnicity distribution was Malay 191 (36.8%), Chinese 189 (36.4%) and Indian 139 (26.8%). The age of Type 2 diabetes diagnosis was (42±14.8) years. The female onset of diabetes mellitus was at age (41.5±13.7) years, while male (42.6±13.7) years. Distribution of diabetic onset by ethnicity was Malay at age (40.7±13.7) years, Chinese (43.2±13.7) years and Indian (42.3±13.7) years. Diabetic onset was classified by age as follow; ≤20 years’ cohort was 33 (6.4%) cases. Group >20- ≤40 years was 190 (36.6%) patients, and category >40- ≤60 years was 270 (52%) subjects. On the other hand, the group >60 years was 22 (4.2%) patients. The range of diagnosis was between 10 and 73 years old. Conclusion: Malay and female have an earlier onset of diabetes than Indian, Chinese and male. More than half of the patients had diabetes between 40 and 60 years old. Diabetes mellitus is becoming more common in younger age <40 years. The age at diagnosis of Type 2 diabetes mellitus has decreased with time.

Keywords: age of onset, diabetes diagnosis, diabetes mellitus, Malaysia, outpatients, type 2 diabetes, retrospective study

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Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar

Abstract:

Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.

Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

Abstract:

Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Pratistha Shrestha

Abstract:

Background: Acrochordons (Skin tags) are common benign skin tumors usually occurring on the neck and major flexors of older people. These range in size from 1 mm to 1cm in diameter and are skin-colored or brownish. A possible association with diabetes mellitus has been suggested in previous studies, but the result is not conclusive. Objective: The aim of this study was to find out the association of diabetes mellitus with acrochordons. Material and Methods: One hundred and two patients were selected for the study. Among them, 51 (males–23 and females–28) with acrochordons were taken as cases, and 51 with other dermatologic diseases after matching age and sex were taken as controls. The patients were selected from OPD of the Department of Dermatology and Venereology in Universal College of Medical Sciences–Teaching Hospital (UCMS-TH). Blood glucose levels, including both fasting plasma glucose and 2-hour post-glucose load, were determined for both case and control and compared. Results: Patients with acrochordons had a significantly higher frequency of diabetes than the control group (p < 0.001). A total of 48.5% and 40% of patients with acrochordons having diabetes were obese and overweight, respectively. Conclusion: There is an increased risk of diabetes mellitus in patients with acrochordons. With regard to the importance of early diagnosis of diabetes, it is recommended a high level of suspicion for diabetes mellitus in patients with acrochordons.

Keywords: acrochordons, diabetes mellitus, obesity, skin tags

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Authors: Jin-Ming Wu, Te-Wei Ho, Yu-Wen Tien

Abstract:

Background: The aim of this population-based study was to determine the occurrence of diabetes and exocrine pancreatic insufficiencies (EPI) on non-diabetes subjects receiving distal pancreatectomy (DP). Method: A nationwide cohort study between 2000 and 2010 was collected from the Taiwan National Health Insurance Research Database. Among 3264 DP patients, we identified 1410 non-diabetes and 966 non-diabetes non-EPI. Results. Of 1410 non-diabetes DP subjects, 312 patients (22.1%) developed newly-diagnosed diabetes after PD. On a multiple logistic regression model, co-morbid hyperlipidemia (odds ratio, 1.640; 95% CI, 1.362–2.763; P < 0.001) and pancreatitis (odds ratio, 2.428; 95% CI, 1.889–3.121; P < 0.001) significantly contributed to higher incidences of diabetes after DP. Moreover, 380 subjects (39.3%) developed EPI, and pancreatic cancer is the statistically significant risk factor (odds ratio, 4.663; 95% CI, 2.108–6.085; P < 0.001). Conclusion: The patients with co-morbid hyperlipidemia and chronic pancreatitis had higher rates of newly-diagnosed diabetes after DP, moreover, pancreatic cancer subjects had higher rates of pancreatic exocrine insufficiency after DP. The clinicians should be alert to follow up glucose metabolism and clinical symptoms of fat intolerance for DP patients.

Keywords: distal pancreatectomy, National database, diabetes, exocrine insufficiency

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Authors: Priya Arora, Ashutosh Mishra

Abstract:

Gene identification, towards the pursuit of mutated genes, leading to Parkinson’s disease, puts forward a challenge towards proactive cure of the disorder itself. Computational analysis is an effective technique for exploring genes in the form of protein sequences, as the theoretical and manual analysis is infeasible. The limitations and effectiveness of a particular computational method are entirely dependent on the previous data that is available for disease identification. The article presents a sequence-based classification method for the identification of genes responsible for Parkinson’s disease. During the initiation phase, the physicochemical properties of amino acids transform protein sequences into a feature vector. The second phase of the method employs Jaccard distances to select negative genes from the candidate population. The third phase involves artificial neural networks for making final predictions. The proposed approach is compared with the state of art methods on the basis of F-measure. The results confirm and estimate the efficiency of the method.

Keywords: disease gene identification, Parkinson’s disease, physicochemical properties of amino acid, protein sequences

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Authors: Pouriya Darabiyan, Kourosh Zarea, Saeed Ghanbari, Aseya Temori, Shokreya Ehsani

Abstract:

Introduction: Diabetes is one of the most common metabolic disorders and is one of the top 10 leading causes of death in adults. Therefore, this study was conducted to investigate the epidemiological prevalence of diabetes in Afghanistan between 2015 and 2019. Methods: This descriptive cross-sectional study was performed using the information of diabetics registered in the system related to the Ministry of Health of Afghanistan from 2015 to 2019. Eventually, people's information, including age, gender, and place of residence, was entered into STATA software version 12 and analyzed using descriptive statistics tests. Results: The study, which was performed on 49,339 people with diabetes in 34 provinces and 8 regions of Afghanistan, found that most of the women studied were 55.2% (272,311) women and had the highest and lowest prevalence in the region. The order is related to South East and South. The average prevalence of diabetes per 10,000 people is about 62.13. Conclusions: The prevalence of diabetes in Afghanistan over a five-year period in men and women is on the rise, requiring more attention from relevant authorities to improve public health and prevent, control and treat chronic diseases such as diabetes. Keywords: Diabetes, Prevalence, Afghanistan, Epidemiology

Keywords: diabetes, prevalence, Afghanistan, epidemiology

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