Search results for: insulin signaling

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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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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Authors: Akbar Nawaz Khan, Abdul Ghaffar, Muhammad Naeem Riaz

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The study was conducted to investigate the phenotypic features, morphometry and production potentialities of indigenous naked neck chicken (NN) of Pakistan under intensive management condition. A total of 35 NN chicks were randomly selected, and the experiment was performed at Poultry and wildlife research section NARC Islamabad for a period of 22 weeks. The predominant plumage color was black and golden while skin color was observed white. The average shank length, leg length, thigh length, keel length, chest breadth, head width, wing space, wing length, body length, body girth, body height and pubic bone width in adult males and females were 69.19 ± 3.34mm, 117.93 ± 4.42mm, 117.93 ± 4.42mm, 90.87 ± 6.53mm, 95.03 ± 4.56mm, 49.77 ± 2.53mm, 30.63 ± 1.50cm, 27.24 ± 2.71cm, 18.88 ± 0.65cm, 17.77 ± 1.01cm, 25.96 ± 0.56cm, 47.81 ± 1.41cm and 35.69 ± 4.09mm respectively. The average age and live body weight of NN chicken at sexual maturity were recorded as 165.85 days and 1269.38 g. While hen-day egg production of NN was recorded as 45%. The present study was aimed to investigate the existence of polymorphism at IGF-I gene in indigenous naked neck chicken through PCR based Restriction Fragment Length Polymorphism. Based on restriction analysis using Hinf I restriction enzyme, three genotypes were detected designated as AA, AC, and CC. Restriction analysis of PCR amplified product showed the presence of DNA fragments of 622, 378, 244 and 191, (genotypes). The PCR-RFLP analysis is easy, cost effective method which permits the easy characterization of IGF-I gene. This showed the investigated IGF-I genes can serve as good molecular markers for marker assisted selection (MAS) concerning growth related traits in chicken.

Keywords: Desi chicken, naked neck, morphology, morphometry, production potential, egg traits, egg geometry, IGF-I, growth, PCR- RFLP, chicken

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Authors: Mythri G., Manjunath ML, Girish Babu M., Shireen Swaliha Quadri

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Background: The increase in diabetes among the elderly is of concern because in addition to the wide range of traditional diabetes complications, evidence has been growing that diabetes is associated with increased risk of cognitive decline. Aims and Objectives: To find out if there is any association between blood sugar levels and short-term and working memory status in patients of type 2 diabetes. Materials and Methods: The study was carried out in 200 individuals aged between 40-65 years consisting of 100 diagnosed cases of Type 2 Diabetes Mellitus and 100 non-diabetics from OPD of Mc Gann Hospital, Shivamogga. Rye’s Auditory Verbal Learning Test, Verbal Fluency Test and Visual Reproduction Test, Working Digit Span Test and Validation Span Test were used to assess short-term and working memory. Fasting and Post Prandial blood sugar levels were estimated. Statistical analysis was done using SPSS 21. Results: Memory test scores of type 2 diabetics were significantly reduced (p < 0.001) when compared to the memory scores of age and gender matched non-diabetics. Fasting blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.837), VFT (r=-0.888), VRT(r=-0.787), WDST (r=-0.795) and VST (r=-0.943). Post- Prandial blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.922), VFT (r=-0.848), VRT(r=-0.707),WDST (r=-0.729) and VST (r=-0.880) Memory scores in all 5 tests were found to be negatively correlated with the FBS and PPBS levels in diabetic patients (p < 0.001). Conclusion: The decreased memory status in diabetic patients may be due to many factors like hyperglycemia, vascular disease, insulin resistance, amyloid deposition and also some of the factor combine to produce additive effects like, type of diabetes, co-morbidities, age of onset, duration of the disease and type of therapy. These observed effects of blood sugar levels of diabetics on memory status are of potential clinical importance because even mild cognitive impairment could interfere with todays’ activities.

Keywords: diabetes, cognition, diabetes, HRV, respiratory medicine

Procedia PDF Downloads 245

Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) and type 1 diabetes mellitus (T1D) are complex disorders with shared genetic components. The association between CD and T1D has been reported in many pediatric series. The aim of our study is to describe the epidemiological, clinical and evolutive characteristics of adult patients presenting this association. Material and Methods: This is a retrospective study including patients diagnosed with CD and T1D, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and June 2016. Results: Among 57 patients with CD, 15 patients had also T1D (26.3%). There are 11 women and 4 men with a median age of 27 years (16-48). All patients developed T1D prior to the diagnosis of CD with an average duration of 47 months between the two diagnosis (6 months-5 years). CD was revealed by recurrent abdominal pain in 11 cases, diarrhea in 10 cases, bloating in 8 cases, constipation in 6 cases and vomiting in 2 cases. Three patients presented cycle disorders with secondary amenorrhea in 2 patients. Anti-Endomysium, anti-transglutaminase and Anti-gliadin antibodies were positive respectively in 57, 54 and 11 cases. The biological tests revealed anemia in 10 cases, secondary to iron deficiency in 6 cases and folate and vitamin B12 deficiency in 4 cases, hypoalbuminaemia in 4 cases, hypocalcemia in 3 cases and hypocholesterolemia in 1 patient. Upper gastrointestinal endoscopy showed an effacement of the folds of the duodenal mucosa in 6 cases and a congestive duodenal mucosa in 3 cases. The macroscopic appearance was normal in the others cases. Microscopic examination showed an aspect of villous atrophy in 57 cases, which was partial in 10 cases and total in 47 cases. After an average follow-up of 3 years 2 months, the evolution was favorable in all patients under gluten-free diet with the necessity of less important doses of insulin in 10 patients. Conclusion: In our study, the prevalence of T1D in adult patients with CD was 26.3%. This association can be attributed to overlapping genetic HLA risk loci. In recent studies, the role of gluten as an important player in the pathogenesis of CD and T1D has been also suggested.

Keywords: celiac disease, gluten, prevalence, type 1 diabetes

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Authors: Peiyin Hung, Katy Kozhimannil, Michelle Casey, Ira Moscovice

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Background/Objective: The loss of obstetric services has been a pressing concern in urban and rural areas nationwide. This study aims to determine factors that contribute to the loss of obstetric care through closures of a hospital or obstetric unit. Methods: Data from 2002-2013 American Hospital Association annual surveys were used to identify hospitals providing obstetric services. We linked these data to Medicare Healthcare Cost Report Information for hospital financial indicators, the US Census Bureau’s American Community Survey for zip-code level characteristics, and Area Health Resource files for county- level clinician supply measures. A discrete-time multinomial logit model was used to determine contributing factors to obstetric unit or hospital closures. Results: Of 3,551 hospitals providing obstetrics services during 2002-2013, 82% kept units open, 12% stopped providing obstetrics services, and 6% closed down completely. State-level variations existed. Factors that significantly increased hospitals’ probability of obstetric unit closures included lower than 250 annual birth volume (adjusted marginal effects [95% confidence interval]=34.1% [28%, 40%]), closer proximity to another hospital with obstetric services (per 10 miles: -1.5% [-2.4, -0.5%]), being in a county with lower family physician supply (-7.8% [-15.0%, -0.6%), being in a zip code with higher percentage of non-white females (per 10%: 10.2% [2.1%, 18.3%]), and with lower income (per $1,000 income: -0.14% [-0.28%, -0.01%]). Conclusions: Over the past 12 years, loss of obstetric services has disproportionately affected areas served by low-volume urban and rural hospitals, non-white and low-income communities, and counties with fewer family physicians, signaling a need to address maternity care access in these communities.

Keywords: access to care, obstetric care, service line discontinuation, hospital, obstetric unit closures

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Authors: Wenpeng You, Maciej Henneberg

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Background: Sugar consumption has been overwhelmingly advocated as a major dietary offender to obesity prevalence. Meat intake has been hypothesized as an obesity contributor in previous publications, but a moderate amount of meat to be included in our daily diet still has been suggested in many dietary guidelines. Comparable sugar and meat exposure data were obtained to assess the difference in relationships between the two major food groups and obesity prevalence at population level. Methods: Population level estimates of obesity and overweight rates, per capita per day exposure of major food groups (meat, sugar, starch crops, fibers, fats and fruits) and total calories, per capita per year GDP, urbanization and physical inactivity prevalence rate were extracted and matched for statistical analysis. Correlation coefficient (Pearson and partial) comparisons with Fisher’s r-to-z transformation and β range (β ± 2 SE) and overlapping in multiple linear regression (Enter and Stepwise) were used to examine potential differences in the relationships between obesity prevalence and sugar exposure and meat exposure respectively. Results: Pearson and partial correlations (controlled for total calories, physical inactivity prevalence, GDP and urbanization) analyses revealed that sugar and meat exposures correlated to obesity and overweight prevalence significantly. Fisher's r-to-z transformation did not show statistically significant difference in Pearson correlation coefficients (z=-0.53, p=0.5961) or partial correlation coefficients (z=-0.04, p=0.9681) between obesity prevalence and both sugar exposure and meat exposure. Both Enter and Stepwise models in multiple linear regression analysis showed that sugar and meat exposure were most significant predictors of obesity prevalence. Great β range overlapping in the Enter (0.289-0.573) and Stepwise (0.294-0.582) models indicated statistically sugar and meat exposure correlated to obesity without significant difference. Conclusion: Worldwide sugar and meat exposure correlated to obesity prevalence at the same extent. Like sugar, minimal meat exposure should also be suggested in the dietary guidelines.

Keywords: meat, sugar, obesity, energy surplus, meat protein, fats, insulin resistance

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Lavrentiadou S. N., Angelou V., Chatzimisios K., Papazoglou L.

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The aim of this study was the isolation and culture of keratinocytes and fibroblasts from feline skin to ultimately create an artificial engineered skin (including dermis and epidermis) useful for the effective treatment of large cutaneous deficits in cats. Epidermal keratinocytes and dermal fibroblasts were freshly isolated from skin biopsies using an 8 mm biopsy punch obtained from 8 healthy cats that had undergone ovariohysterectomy. The owner’s consent was obtained. All cats had a complete blood count and a serum biochemical analysis and were screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) preoperatively. The samples were cut into small pieces and incubated with collagenase (2 mg/ml) for 5-6 hours. Following digestion, cutaneous cells were filtered through a 100 μm cell strainer, washed with DMEM, and grown in DMEM supplemented with 10% FBS. The undigested epidermis was washed with DMEM and incubated with 0.05% Trypsin/0.02% EDTA (TE) solution. Keratinocytes recovered in the TE solution were filtered through a 100 μm and a 40 μm cell strainer and, following washing, were grown on a collagen type I matrix in DMEM: F12 (3:1) medium supplemented with 10% FΒS, 1 μm hydrocortisone, 1 μm isoproterenol and 0.1 μm insulin. Both fibroblasts and keratinocytes were grown in a humidified atmosphere with 5% CO2 at 37oC. The medium was changed twice a week and cells were cultured up to passage 4. Cells were grown to 70-85% confluency, at which point they were trypsinized and subcultured in a 1:4 dilution. The majority of the cells in each passage were transferred to a freezing medium and stored at -80oC. Fibroblasts were frozen in DMEM supplemented with 30% FBS and 10% DMSO, whereas keratinocytes were frozen in a complete keratinocyte growth medium supplemented with 10% DMSO. Both cell types were thawed and successfully grown as described above. Therefore, we can create a bank of fibroblasts and keratinocytes, from which we can recover cells for further culture and use for the generation of skin equivalent in vitro. In conclusion, cutaneous cell isolation and cell culture and expansion were successfully developed. To the authors’ best knowledge, this is the first study reporting isolation and culture of keratinocytes and fibroblasts from feline skin. However, these are preliminary results and thus, the development of autologous-engineered feline skin is still in process.

Keywords: cat, fibroblasts, keratinocytes, skin equivalent, wound

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Authors: Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Veronique Dhennin, Jean-Marc Lacorte, Philippe Froguel, Amelie Bonnefond

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In the population of Guadeloupe Island (472,124 inhabitants and 80% of subjects of African descent), overweight and obesity were estimated at 23% and 9% respectively among children. High prevalence of diabetes has been reported (~10%) in the adult population. Nevertheless, no study has investigated the contribution of gene mutations to childhood obesity in this population. We aimed to investigate rare genetic mutations in genes involved in monogenic obesity or diabetes in obese Afro-Caribbean children from Guadeloupe Island using next-generation sequencing. The present investigation included unrelated obese children, from a previous study on overweight conducted in Guadeloupe Island in 2013. We sequenced coding regions of 59 genes involved in monogenic obesity or diabetes. A total of 25 obese schoolchildren (with Z-score of body mass index [BMI]: 2.0 to 2.8) were screened for rare mutations (non-synonymous, splice-site, or insertion/deletion) in 59 genes. Mean age of the study population was 12.4 ± 1.1 years. Seventeen children (68%) had insulin-resistance (HOMA-IR > 3.16). A family history of obesity (mother or father) was observed in eight children and three of the accompanying parent presented with type 2 diabetes. None of the children had gonadotrophic abnormality or mental retardation. We detected five rare heterozygous mutations, in four genes involved in monogenic obesity, in five different obese children: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations which were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations which were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutation in ABCC8 or KCNJ11 (involved in monogenic diabetes), which were of uncertain significance (KCNJ11 p.Val13Met, KCNJ11 p.Val151Met, ABCC8 p.Lys1521Asn and ABCC8 p.Ala625Val). Rare pathogenic or likely pathogenic mutations, linked to severe obesity were detected in more than 15% of this Afro-Caribbean population at high risk of obesity and type 2 diabetes.

Keywords: childhood obesity, MC4R, monogenic obesity, SIM1

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Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani

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Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.

Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ

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Authors: Rumana Keyani, Haleema Sadia, Asia Nosheen, Rabia Naz, Humaira Yasmin, Sidra Zahoor

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Tomato is a significant crop of the world and is one of the staple foods of Pakistan. A vast number of plant pathogens from simple viruses to complex parasites cause diseases in tomatoes but fungal infection in our country is quite high. Sometimes the symptoms are too harsh destroying the crop altogether. Countries like our own with continuously increasing massive population and limited resources cannot afford such an economic loss. There is an array of morphological, genetic, biochemical and molecular processes involved in plant resistance mechanisms to biotic stress. The study of different metabolic pathways like Jasmonic acid (JA) pathways and most importantly signaling molecules like ROS/RNS and their redoxin enzymes i.e. TRX and NRX is crucial to disease management, contributing to healthy plant growth. So, improving tolerance in crop plants against biotic stresses is a dire need of our country and world as whole. In the current study, fungal pathogenic strains Alternaria solani and Rhizoctonia solani were used to inoculate tomatoes to check the defense responses of tomato plant against these pathogens at molecular as well as phenotypic level with jasmonic acid and spermidine pretreatment. All the growth parameters (root and shoot length, dry and weight root, shoot weight measured 7 days post-inoculation, exhibited that infection drastically declined the growth of the plant whereas jasmonic acid and spermidine assisted the plants to cope up with the infection. Thus, JA and Spermidine treatments maintained comparatively better growth factors. Antioxidant assays and expression analysis through real time quantitative PCR following time course experiment at 24, 48 and 72 hours intervals also exhibited that activation of JA defense genes and a polyamine Spermidine helps in mediating tomato responses against fungal infection when used alone but the two treatments combined mask the effect of each other.

Keywords: fungal infection, jasmonic acid defence, tomato, spermidine

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Authors: Boris Bajer, Andrea Havranova, Miroslav Vlcek, Richard Imrich, Adela Penesova

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Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, and also prevent cardiovascular diseases, as it showed many studies (the Finnish Diabetes Prevention Study, Diabetes Prevention Program (DPP), . the China Da Qing Diabetes Prevention Study, etc.) Therefore the aim of our study was to compare the effect of intensified lifestyle intervention on cardiometabolic parameters. Methods: It is an ongoing randomized interventional clinical study (NCT02325804) focused on the reduction of body weight/fat. Intervention: hypocaloric diet (30% restriction of calories) and physical activity 150 minutes/week. Before and after 8 weeks of intervention all patients underwent complete medical examination (measurement of physical fitness, resting metabolic rate (RMR), body composition analysis, oral glucose tolerance test, parameters of lipid metabolism, and other cardiometabolic risk factors. Results: So far 39 patients finished the intervention. The average reduction of body weight was 6,8 + 4,9 kg (0-15 kg; p=0,0006), accompanied with significant reduction of body fat percentage (p ≤ 0,0001), amount of fat mass (p=0,03), waist circumference (p=0.02). Amount of lean mass and RMR remained unchanged. Heart rate (p=0,02), systolic and diastolic blood pressure was reduced (p=0,01 p=0,02 resp.) as well as insulin sensitivity was improved. Lipid parameters also changed - cholesterol, LDL decreased (p=0,05, p=0,04 resp.), while triglycerides showed tendency to decrease (p=0,055). Liver function improved, alanine aminotrasnferase (ALT) were reduced (p=0,01). Physical fitness significantly improved (as measure VO2 max (p=0,02). Conclusion: Results of our study are in line with previous results about the beneficial effect of intensive lifestyle changes on the reduction of cardiometabolic risk factors and improvement of liver function. Supported by grants APVV 15-0228; VEGA 2/0161/16

Keywords: obesity, weight loss, diet lipids, blood pressure, liver enzymes

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Authors: Shadia Al-Bahlani, Ruqaya Al-Rashdi, Shadia Al-Sinawi, Maya Al-Bahri

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Background: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. The role of clapins in pathogenesis and tumor progression has been studied in certain cancer types; however, its definite role is not yet established in breast cancer especially in the TNBC subtype. Objectives: This study aims to measure calpain-1 expression and correlate this measurement with the proliferating/apoptotic index as well with the prognostic factors in TNBC patients’ tissue. Materials and Methods: Thirty nine paraffin blocks from patients diagnosed with TNBC were used to measure the expression of calpain-1 and Ki-67 (proliferating marker) proteins using immunohistochemistry. Apoptosis was assessed morphological and biochemically using conventional Haematoxylin and Eosin (H&E) staining method and terminal deoxynucleotidyl transferase-mediate dUTP nick and labeling (TUNEL) assay respectively. Data was statistically analyzed using Pearson X2 test of association. Results: Calpain-1 content was visualized in the nucleus of the TNBC cells and its expression varied from low to high among the patients tissue. Calpain expression showed no significant correlation with the proliferating/apoptotic index as well with the clinicopathological variables. Apoptotic counts quantified by H&E staining showed significant association with the apoptotic TUNEL assay, validating both approaches. Conclusion: Although calpain-1 expression showed no significant association with the clinical outcome, its variable level of expression might indicate a hidden role in breast cancer tissue. Larger number of samples and different mode of assessments are needed to fully investigate such role. Exploring the involvement of calpain-1 in cancer progression might help in considering it as a biomarker of breast cancer.

Keywords: breast cancer, calpain, apoptosis, prognosis

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Ishfaq A. Bukhari, Bassem Yousef Sheikh, Abdulrahman Almotrefi, Osama Yousaf, Amer Mahmood

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Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. Olive oil is rich in monounsaturated fatty acids, and has been reported for variety of beneficial cardiovascular effects including blood pressure lowering, anti-platelet, anti-diabetic and anti-inflammatory effects. Growing number evidences from preclinical and clinical studies have shown that olive oil improves insulin resistance, decrease vessels stiffness and prevent thromboembolism. We evaluated the effects of olive against streptozotocin-induced physiological disorders in the animal models of diabetes and ischemia and reperfusion (I/R)- induced cardiac arrhythmias. Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), rats were treated for two months with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose, body weight were monitored every 14 days. At the end of the treatment rats were sacrificed hearts were isolated for mounting on langedorff’s apparatus. The blood glucose and body weight was not significantly different in the control and olive treated animals. The control diabetic animals exhibited 100% incidence of I/R –induced ventricular fibrillation which was reduced to 0% with olive oil, treatment. The duration of ventricular fibrillation reduced from 98.8± 2.3 (control) to 0 seconds in the olive oil treated group. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The biochemical analysis of the cardiac tissues showed that diabetes and I/R produce marked pathological changes in the cardiomyocytes including decreased glutathione (GSH) and increased oxidative stress (Malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. These finding indicates that olive possesses cardiac protective properties. Further studies are under way in our lab to explore the mechanism of the cardio-protective effect of olive oil.

Keywords: diabeties, ischemia-reperfusion, olive oil, rats heart

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Authors: Ricardo de Oliveira Orsi, Aline Astolfi, Daniel Diego Mendes, Isabella Cristina de Castro Lippi, Jaine da Luz Scheffer, Yan Souza Lima, Juliana Lunardi, Giovanna do Padro Ribeiro, Samir Moura Kadri

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NECTAR Brazilian group (Center of Education, Science, and Technology in Rational Beekeeping) conducted studies on the pesticides honey bees effects using the transcriptome sequencing (RNA-Seq) analyzes for gene expression studies. In this way, we analyzed the effects of Pyraclostrobin and Fipronil on the honey bees with 21 old-days (forager) in laboratory conditions. For this, frames containing sealed brood were removed from the beehives and maintenance on the stove (32°C and 75% humidity) until the bees were born. So, newly emerged workers were marked on the pronotum with a non-toxic pen and reintroduced into their original hives. After 21 days, 120 marked bees were collected with an entomological forces and immediately stored in Petri dishes, perforated to ensure ventilation, and kept fasted for 3 hours. These honeybees were exposed to food contaminated or not with the sublethal dose of Pyraclostrobin (850 ppb/bee) or Fipronil (2.5 ppb/bee). After four hours of exposure, 15 bees from each treatment were referred to transcriptome analysis. Total RNA analysis was extracted from the brain pools (03 brains per pool) using the TRIzol® reagent protocol according to the manufacturer's instructions. cDNA libraries were constructed, and the FASTQC program was used to check adapter content and assess the quality of raw reads. Differential expression analysis was performed with the DESeq2 package. Genes that had an adjusted value of less than 0.05 were considered to be significantly up-regulated. Regarding the Pyraclostrobin, alterations were observed in the pattern of 17 gene related to of antioxidant system, cellular respiration, glucose metabolism, and regulation of juvenile hormone and the hormone insulin. Glyphosate altered the 10 gene related to the digestive system, exoskeleton composition, vitamin E transport, and antioxidant system. The results indicate that the necessity of studies using the sublethal doses to evaluate the pesticides uses and risks on crops and its effects on the honey bees.

Keywords: beekeeping, honey bees, pesticides, transcriptome

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Authors: Vivek Saxena, Shreshtha Saxena

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Background: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance first recognized during pregnancy. Uncontrolled or untreated GDM is associated with various adverse outcomes to the maternal and fetal health. Overt diabetes mellitus may also develop in such patients. It is universally accepted fact that first and foremost management to treat GDM is dietary control and lifestyle modification even before starting any oral hypoglycemic agent (OHA) or insulin. So, proper dietary management and little changes in the patient’s lifestyle are very effective for reducing her plasma glucose level. Objectives: Proper counselling of the patients and flexibility in their lifestyle and diet can effectively control the plasma glucose level in GDM patients. Methods: Total 60 GDM patients of age > 18 years were taken. We had three counselling sessions with the patient and other members of the family like husband, parents, and in-laws at different intervals, discussed their lifestyle and diet pattern, helped them to eliminate the factors those had an adverse effect on plasma glucose level and promoted them to acquire a healthy lifestyle. We have counselled the patient and her family member separately and then together also. They have explained how increased plasma glucose level can be effectively controlled with the little modification in their diet and routine activities. They were also taught to remain stress-free during their rest of antenatal period. We have excluded the patients from our study who were diabetic before pregnancy and patients with other comorbid illnesses like hypothyroidism and valvular heart disease. Results and conclusions: Results were very rewarding as patients could acquire a lifestyle of their choice. They were happy because extra pill burden was not there. All the 60 patients were normoglycemic in remaining antenatal period, 48 patients were delivered normally and 12 patients underwent cesarean section due to various reasons.Regular counselling of the patients regarding their disease and little alterations in diet and lifestyle controlled the plasma glucose level much effectively. The things were more easier and effective when we included other family members during our counselling session because they play a major role in patient’s day to day activity and influence her life.

Keywords: dietary management, gestational diabetes mellitus, impaired glucose tolerance, oral hypoglycemic agent, pregnancy

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Authors: Sunil Kumar, Uday C. Ghoshal

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Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.

Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Abhinav Kumar Rajverma, Arun Kumar Misra, Abhijeet Chandra

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Family involvement in business is universal across countries, with varying characteristics. Firms of developed economies have diffused ownership structure; however, that of emerging markets have concentrated ownership structure, having resemblance with that of family firms. Optimization of dividend payout and leverage are very crucial for firm’s valuation. This paper studies dividend paying behavior of National Stock Exchange listed Indian firms from financial year 2007 to 2016. The final sample consists of 422 firms and of these more than 49% (207) are family firms. Results reveal that family firms pay lower dividend and are more leveraged compared to non-family firms. This unique data set helps to understand dividend behavior and capital structure of sample firms over a long-time period and across varying family ownership concentration. Using panel regression models, this paper examines factors affecting dividend payout and capital structure and establishes a link between the two using Two-stage Least Squares regression model. Profitability shows a positive impact on dividend and negative impact on leverage, confirming signaling and pecking order theory. Further, findings support bankruptcy theory as firm size has a positive relation with dividend and leverage and volatility shows a negative relation with both dividend and leverage. Findings are also consistent with agency theory, family ownership concentration has negative relation with both dividend payments and leverage. Further, the impact of family ownership control confirms the similar finding. The study further reveals that firms with high family ownership concentration (family control) do have an impact on determining the level of private benefits. Institutional ownership is not significant for dividend payments. However, it shows significant negative relation with leverage for both family and non-family firms. Dividend payout and leverage show mixed association with each other. This paper provides evidence of how varying level of family ownership concentration and ownership control influences the dividend policy and capital structure of firms in an emerging market like India and it can have significant contribution towards understanding and formulating corporate dividend policy decisions and capital structure for emerging economies, where majority of firms exhibit behavior of family firm.

Keywords: dividend, family firms, leverage, ownership structure

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Mitesh Rathod, Jungho Ahn, Noo Li Jeon, Junghoon Lee

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Endothelial cells respond to cues from both biochemical as well as micro mechanical environment. Significant effort has been directed to understand the effects of biochemical signaling, however, relatively little is known about regulation of endothelial cell biology by the micro mechanical environment. Numerous studies have been performed to understand how physical forces regulate endothelial cell behavior. In this regard, past studies have majorly focused on exploring how fluid shear stress governs endothelial cell behavior. Parallel plate flow chambers and rectangular microchannels are routinely employed for applying fluid shear force on endothelial cells. However, these studies fall short in mimicking the in vivo like micro environment from topological aspects. Few studies have only used circular microchannels to replicate in vivo like condition. Seldom efforts have been directed to elucidate the combined effect of topology, substrate rigidity and fluid shear stress on endothelial cell response. In this regard, we demonstrate a facile fabrication process to develop a hybrid polydimethylsiloxane microfluidic platform to study endothelial cell biology. On a single chip microchannels with different cross sections i.e., circular, rectangular and square have been fabricated. In addition, our fabrication approach allows variation in the substrate rigidity along the channel length. Two different variants of polydimethylsiloxane, namely Sylgard 184 and Sylgard 527, were utilized to achieve the variation in rigidity. Moreover, our approach also enables in creating Y bifurcation circular microchannels. Our microfluidic platform thus facilitates for conducting studies pertaining to endothelial cell morphology with respect to change in topology, substrate rigidity and fluid flow on a single chip. The hybrid platform was tested by culturing Human Umbilical Vein Endothelial Cells in circular microchannels with varying substrate rigidity, and exposed to fluid shear stress of 12 dynes/cm² and static conditions. Results indicate the cell area response to flow induced shear stress was governed by the underlying substrate mechanics.

Keywords: hybrid, microfluidic platform, PDMS, shear flow, substrate rigidity

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Authors: Josline Salib, Sayed El-Toumy, Abeer Salama, Enayat Omara, Emad Hassan

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Diabetic nephropathy is an important cause of morbidity and mortality and is now among the most common causes of end-stage renal failure (ESRF) in developed countries. Thus, the aim of the present study was to investigate the phenolic compounds content of Cichorium intybus aerial parts extracts as well as the therapeutic effects on diabetic nephropathy, oxidative stress, and anti-inflammatory by characterizing biochemical, histopathological changes and immunohistochemistry in an experimental diabetic rat model as compared with Amaryl. Ten known compounds of flavonoids, coumarins and phenolic acid derivatives were isolated from the C. intybus aqueous methanolic extract. Structures of the isolated compounds were established by chromatography, UV and 1D⁄2D 1H⁄ 13C spectroscopy. The aqueous methanol extract of C. intybus aerial parts was administered to Streptozotocin diabetes rats at doses (100 and 200 mg/kg) for 21 days. After treatment, blood glucose, serum insulin, urea, creatinine, and TNF-α were evaluated. Enzymatic scavengers including catalase (CAT), glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) were determined to evaluate the oxidative status in the renal tissue. Diabetic rats treated with C. intybus extract showed a dose-dependent reduction of fasting blood glucose and kidney antioxidant status in comparison to the diabetic control group. The extract was able to enhance the antioxidant defenses of the kidney by increasing the reduced GSH and CAT content and decreasing MDA content in addition to significantly decreasing kidney nitric oxide content compared to diabetic control rats. Furthermore, the histopathological findings in C. intybus extract administered rats were observed at markedly lesser extent than the diabetic control group. Also, inducible nitric oxide synthase (iNOS) levels were decreased significantly after the administration of high-dose C. intybus extract in diabetic rats. Showing significant antihyperglycemic and antioxidant properties of C. intybus aerial parts extract, which is attributed to its polyphenolic content, may offer a potential source for the treatment of diabetes.

Keywords: antioxidant activity, anti-diabetic nephropathy, cichorium intybus aerial parts, phenolic compounds

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Authors: Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

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Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice; however, commercial substitutes, such as BeePro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism. Gene ontology enrichment revealed that, compared with poor diet (carbohydrates (C)), bees fed pollen (P > C), BeePro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions and superior proteolysis. The superiority of the pollen diet was also evident through the remarkable overexpression of vitellogenin in bees fed pollen instead of MegaBee or BeePro. Upregulation of bioprocesses under carbohydrates feeding compared to pollen (C > P) provided a clear poor nutritional status, uncovering stark expression changes that were slight or absent relatively to BeePro (C > B) or MegaBee (C > M). Poor diet feeding (C > P) induced starvation response genes and hippo signaling pathway, while it repressed growth through different mechanisms. Carbohydrate feeding (C > P) also elicited ‘adult behavior’, and developmental processes suggesting transition to foraging. Finally, it altered the ‘circadian rhythm’, reflecting the role of this mechanism in the adaptation to nutritional stress in mammals. Nosema-infected bees fed pollen compared to carbohydrates (PN > CN) upheld certain bioprocesses of uninfected bees (P > C). Poor nutritional status was more apparent against pollen (CN > PN) than BeePro (CN > BN) or MegaBee (CN > MN). Nosema accentuated the effects of malnutrition since more starvation-response genes and stress response mechanisms were upregulated in CN > PN compared to C > P. The bioprocess ‘Macromolecular complex assembly’ was also enriched in CN > PN, and involved genes associated with human HIV and/or influenza, thus providing potential candidates for bee-Nosema interactions. Finally, the enzyme Duox emerged as essential for guts defense in bees, similarly to Drosophila. These results provide evidence of the superior nutritional status of bees fed pollen instead of artificial substitutes in terms of overall health, even in the presence of a pathogen.

Keywords: honeybee, immunity, Nosema, nutrition, RNA-seq

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Authors: Agnieszka Rolinska, Marta Makara-Studzinska

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Introduction: In recent years, there has been an intensive development of research into the physiological relationships between the experienced stress and obesity. Moreover, strong chronic stress leads to the disorganization of a person’s activeness on various levels of functioning, including the behavioral and cognitive sphere (also in one’s diet). Aim: The present work addresses the following research questions: Is there a relationship between an increase in stress related to the disease and the need for the cyclicality of diabetologic education in gestational diabetes? Are there any differences in terms of the experienced stress during the last three months of pregnancy in women with gestational diabetes and in normal pregnancy between the patients with normal weight gains and those with abnormal weight gains? Are there any differences in terms of stress coping styles in women with gestational diabetes and in normal pregnancy between the patients with normal weight gains and those with abnormal weight gains? Method: The study involved pregnant women with gestational diabetes (treated with diet, without insulin therapy) and in normal pregnancy – 206 women in total. The following psychometric tools were employed: Perceived Stress Scale (PSS; Cohen, Kamarck, Mermelstein), Coping Inventory for Stressful Situations (CISS; Endler, Parker) and authors’ own questionnaire. Gestational diabetes mellitus was diagnosed on the basis of the results of fasting oral glucose tolerance test (75 g OGTT). Body weight measurements were confirmed in a diagnostic interview, taking into account medical data. Regularities in weight gains in pregnancy were determined according to the recommendations of the Polish Gynecological Society and American norms determined by the Institute of Medicine (IOM). Conclusions: An increase in stress related to the disease varies in patients with differing requirements for the cyclical nature of diabetologic education (i.e. education which is systematically repeated). There are no differences in terms of recently experienced stress and stress coping styles between women with gestational diabetes and those in normal pregnancy. There is a relationship between weight gains in pregnancy and the stress experienced in life as well as stress coping styles – both in pregnancy complicated by diabetes and in physiological pregnancy. In the discussion of the obtained results, the authors refer to scientific reports from English-language magazines of international range.

Keywords: diabetologic education, gestational diabetes, stress, weight gain in pregnancy

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Ali Showail Ali Alasmari

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Introduction: Cataract is the loss of transparency of the lens inside the eye. It is the most common cause of visual loss and blindness worldwide. This study provides a systemic review of the recent findings on the association of vitamin D, and vitamin B12, and their possible role in preventing cataracts in senile (S) and diabetic mellitus (DM) patient groups. Objective: This study was intended to establish and investigate if there is any role between vitamin D and vitamin B12? Secondly, the connection between serum level of vitamin D and vitamin B12 in cataract incidence senile (s) vs. diabetic mellitus (DM) cataract patient groups. Furthermore, to evaluate and analyze cataract occurrence regarding vitamin D and vitamin B12 levels with other risk factors. Finally, to evaluate lens opacities pre and post treatment with vitamin D and vitaminB12 linked to age and visual acuity loss in both senile(S) and diabetic mellitus (DM) cataract patients’ groups. Methods: This study conducted at the ophthalmology clinic at Muhyail General Hospital. Select a prospective case-control to study the effect of vitamin D and Vit B12 on senile(S) cataracts that caused by age and diabetic mellitus (DM)cataract patients; then we compare these two groups. This study prospectively enrolled a total of 50 samples, 25 with senile cataract and 25 with diabetic cataract, from ophthalmology clinic at Muhyail General Hospital. Measuring 25-hydroxy vitamin D and vitamin B12 level concentrations in the assigned samples. Analyses were performed using SAS (statistical analysis software) program. Results: The most important finding in this study was that the senile(s) cataract patients’ group greatly benefited by the combination therapy of vitamin D, and Vitamin B12 reached (28.5±1.50 and 521.1±21.10) respectively; on the contrary, the diabetic cataract patient group hardly shows any significant improvement (21.5 ± 1.00 and 197.2 ± 7.20) respectively. This is because of the Metformin, the first line drug for treating diabetes, has been reported to potentially decrease vitamin B-12 status. This epigenetic modification was correlated with the diabetic mellitus (DM) cataract patients’ group not responding. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. There was no significant difference between the age, body mass index (BMI), the mean of Vit-D pre-treatments, and the mean values of Hemoglobin A1C of both senile (S) and diabetic mellitus (DM) cataract patient groups. On other hand, there was a highly significant difference between the mean values of glucose levels in both senile (S) and diabetic mellitus (DM) cataract patient groups. Conclusion: Here we conclude that diabetic mellitus (DM) cataract patient group hardly benefited from this combination therapy vitamin D and vitamin B12; on the other hand senile patient group (s) benefited a lot from the therapy.

Keywords: cataract patients, senile, diabetes mellitus, vitamin B12, vitamin D, Muhyail General Hospital, Saudi Arabia

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