Search results for: mismatch repair protein

Authors: Cangir Uyarlar, Ismail Bayram, Ibrahim Sadi Cetingul, Mustafa Kabu, Eyup Eren Gultepe

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This study was conducted to determine the effects of organic chromium and organic chromium+propylene glycol on milk yield and some blood parameters related with liver fatty acid metabolism in early lactation dairy cows. Thirty multiparous Holstein dairy cows were used as study material. Cows assigned to three groups as control (C), chromium (Cr) and chromium+propylene glycol (CP). Live weight, parity and body condition score were used as covariates for statistical analyses. The study began at calving and finished at 3 weeks after calving. All cows were consumed same diet. Organic chromium and organic chromium+propylene glycol were orally administrated to cows in treatment groups shortly after the morning milking. Blood samples were collected from all cows on 0 (calving), 3rd, 6th, 9th, 12th, 15th, 18th, 21th days after calving. Then, samples were analyzed for BHBA (Betahydroxybutiric acids), NEFA (Non Esterified Fatty Acids), urea, total protein (TP) and glucose concentrations. Weekly milk yields were calculated from daily milk data on farm. Organic chromium treatment had no significant differences on serum biochemical parameters and milk yields. However, administration of organic chromium and propylene glycol combination decreased serum urea and total protein concentration, helped to protection from subclinical metabolic diseases via decreasing serum NEFA and BHBA concentrations. Also, this combination decreased serum glucose levels of cows. Neither only chromium nor chromium and propylene glycol combination did not affect milk yield throughout the study. These findings were suggested that orally administrations of chromium and propylene glycol combination improved liver glucose and fatty acid metabolism, decreased serum parameters which are representing subclinical diseases in early lactation dairy cows.

Keywords: chromium, early lactation dairy cows, propylene glycol, milk yield

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Authors: Salah Belaidi

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We have carried out extensive and in-depth research to search for bioactive compounds based on Algerian plants. A selection of 50 ligands from Algerian medicinal plants. Several compounds used in herbal medicine have been drawn using Marvin Sketch software. We determined the three-dimensional structures of the ligands with the MMFF94 force field in order to prepare these ligands for molecular docking. The 3D protein structure of the SARS-CoV-2 main protease was taken from the Protein Data Bank. We used AutoDockVina software to apply molecular docking. The hydrogen atoms were added during the molecular docking process, and all the twist bonds of the ligands were added using the (ligand) module in the AutoDock software. The COVID-19 main protease (Mpro) is a key enzyme that plays a vital role in viral transcription and mediating replication, so it is a very attractive drug target for SARS-CoV-2. In this work, an evaluation was carried out on the biologically active compounds present in these selected medicinal plants as effective inhibitors of the protease enzyme of COVID-19, with an in-depth computational calculation of the molecular docking using the Autodock Vina software. The top 7 ligands: Phloroglucinol, Afzelin, Myricetin-3-O- rutinosidTricin 7-neohesperidoside, Silybin, Silychristinthat and Kaempferol are selected among the 50 molecules studied which are Algerian medicinal plants, whose selection is based on the best binding energy which is relatively low compared to the reference molecule with binding affinities of -9.3, -9.3, -9, -8.9, -8 .5, 8.3 and -8.3 kcal mol-1 respectively. Then, we analyzed the ADME properties of the best7 ligands using the web server SwissADME. Two ligands (Silybin, Silychristin) were found to be potential candidates for the discovery and design of novel drug inhibitors of the protease enzyme of SARS-CoV-2. The stability of the two ligands in complexing with the Mpro protease was validated by molecular dynamics simulation; they revealed a stable trajectory in both techniques, RMSD and RMSF, by showing molecular properties with coherent interactions in molecular dynamics simulations. Finally, we conclude that the Silybin ligand forms a more stable complex with the Mpro protease compared to the Silychristin ligand.

Keywords: COVID-19, medicinal plants, molecular docking, ADME properties, molecular dynamics

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Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Fitria D. Ayuningtyas, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of TSD (Temperature-dependent Sex Determination, TSD) animals which sex is determined by the egg’s incubation temperature. GSD (Genotypic Sex Determination) homologous genes such as Wilms’ Tumor (Wt1) and Forkhead Box L2 (FoxL2) play a role in TSD animal sex determination process. Wt1 plays a role in both male pathway, as a transcription factor for Sf1 gene and in female pathway, as a transcription factor for Dax1. FoxL2 plays a role specifically in female sex determination, and known as transcriptional factor for Aromatase gene. Until now, research on the pattern of Wt1 and FoxL2 genes expression in C.mydas has not been conducted yet. The aim of this research is to know the pattern of Wt1 and FoxL2 genes expression in Mesonephros-Gonad (MG) complexes of Chelonia mydas embryos incubated in masculinizing temperature (MT) and feminizing temperature (FT). Eggs of C.mydas incubated in 3 different stage of TSP (Thermosensitive Period) at masculinizing temperature (26±10C, MT) and feminizing temperature (31±10C FT). Mesonefros-gonad complexes were isolated at Pre-TSP stage (FT at days 14th, MT at days 24th), TSP stage (FT at days 24th, MT at days 36th) and differentiated stage (FT at days 40th, MT at days 58th). RNA from mesonephros-gonad (MG) complexes were converted into cDNA by RT-PCR process, and the pattern of Wt1 and FoxL2 genes expression is analyzed by quantitative Real Time PCR (qPCR) method, β-actin gene is used as an internal control. The pattern of Wt1 gene expression in Pre-TSP stage was almost the same between MG complexes incubated at MT or FT, while TSP and differentiation stage, the pattern of Wt1 gene expression in MG complexes incubated at MT or FT was increased. Wt1 gene expression of MG complexes that incubated at FT was higher than at MT. There was a difference pattern between Wt1 gene expression in this research compared to the previous research in protein level. It could be assumed that the difference caused by post-transcriptional regulation mechanisms before mRNA of Wt1 gene translated into protein structure. The pattern of FoxL2 gene expression in Pre-TSP stage was almost the same between MG complexes that incubated at MT and FT, and increased in both TSP and differentiated stage. The FoxL2 gene expression in MG complexes that incubated in FT is higher than MT on TSP and differentiated stage. Based on the results of this research, it can be assumed that Wt1 and FoxL2 gene were expressed in MG complexes that incubated both at MT and FT since Pre-TSP stage. The pattern of Wt1 gene expression was increased in every stage of gonadal development, and so do the pattern of FoxL2 gene expression. Wt1 and FoxL2 gene expressions were higher in MG complexes incubated at FT than MT.

Keywords: chelonia mydas, FoxL2, gene expression, TSD, Wt1

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Authors: Hamza Zidoum

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This paper investigates the impact of human genetic variation on the function of human proteins using machine-learning algorithms. Single-Nucleotide Polymorphism represents the most common form of human genome variation. We focus on the single amino-acid polymorphism located in the coding region as they can affect the protein function leading to pathologic phenotypic change. We use several supervised Machine Learning methods to identify structural properties correlated with increased risk of the missense mutation being damaging. SVM associated with Principal Component Analysis give the best performance.

Keywords: single-nucleotide polymorphism, machine learning, feature selection, SVM

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Authors: Leila Safazadeh, Brad Berron

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Self-assembled monolayers have tremendous impact in interfacial science, due to the unique opportunity they offer to tailor surface properties. Low-density self-assembled monolayers are an emerging class of monolayers where the environment-interfacing portion of the adsorbate has a greater level of conformational freedom when compared to traditional monolayer chemistries. This greater range of motion and increased spacing between surface-bound molecules offers new opportunities in tailoring adsorption phenomena in sensing systems. In particular, we expect low-density surfaces to offer a unique opportunity to intercalate surface bound ligands into the secondary structure of protiens and other macromolecules. Additionally, as many conventional sensing surfaces are built upon gold surfaces (SPR or QCM), these surfaces must be compatible with gold substrates. Here, we present the first stable method of generating low-density self assembled monolayer surfaces on gold for the analysis of their interactions with protein targets. Our approach is based on the 2:1 addition of thiol-yne chemistry to develop new classes of y-shaped adsorbates on gold, where the environment-interfacing group is spaced laterally from neighboring chemical groups. This technique involves an initial deposition of a crystalline monolayer of 1,10 decanedithiol on the gold substrate, followed by grafting of a low-packed monolayer on through a photoinitiated thiol-yne reaction in presence of light. Orthogonality of the thiol-yne chemistry (commonly referred to as a click chemistry) allows for preparation of low-density monolayers with variety of functional groups. To date, carboxyl, amine, alcohol, and alkyl terminated monolayers have been prepared using this core technology. Results from surface characterization techniques such as FTIR, contact angle goniometry and electrochemical impedance spectroscopy confirm the proposed low chain-chain interactions of the environment interfacing groups. Reductive desorption measurements suggest a higher stability for the click-LDMs compared to traditional SAMs, along with the equivalent packing density at the substrate interface, which confirms the proposed stability of the monolayer-gold interface. In addition, contact angle measurements change in the presence of an applied potential, supporting our description of a surface structure which allows the alkyl chains to freely orient themselves in response to different environments. We are studying the differences in protein adsorption phenomena between well packed and our loosely packed surfaces, and we expect this data will be ready to present at the GRC meeting. This work aims to contribute biotechnology science in the following manner: Molecularly imprinted polymers are a promising recognition mode with several advantages over natural antibodies in the recognition of small molecules. However, because of their bulk polymer structure, they are poorly suited for the rapid diffusion desired for recognition of proteins and other macromolecules. Molecularly imprinted monolayers are an emerging class of materials where the surface is imprinted, and there is not a bulk material to impede mass transfer. Further, the short distance between the binding site and the signal transduction material improves many modes of detection. My dissertation project is to develop a new chemistry for protein-imprinted self-assembled monolayers on gold, for incorporation into SPR sensors. Our unique contribution is the spatial imprinting of not only physical cues (seen in current imprinted monolayer techniques), but to also incorporate complementary chemical cues. This is accomplished through a photo-click grafting of preassembled ligands around a protein template. This conference is important for my development as a graduate student to broaden my appreciation of the sensor development beyond surface chemistry.

Keywords: low-density self-assembled monolayers, thiol-yne click reaction, molecular imprinting

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Authors: Ahmed Elgadri

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In the last thirty years, studies on cross-cultural pragmatics in general and apology strategies in specific have focused on western and East-Asian societies. A small volume of research has been conducted in investigating speech acts production by Arabic dialect speakers. Therefore, this study investigated the apology strategies used by Libyan Arabic speakers using an online Discourse Completion Task (DCT) questionnaire. The DCT consisted of six situations covering different social contexts. The survey was written in Libyan Arabic dialect to help generate vernacular speech as much as possible. The participants were 25 Libyan nationals, 12 females, and 13 males. Also, to get a deeper understanding of the motivation behind the use of certain strategies, the researcher interviewed four participants using the Libyan Arabic dialect as well. The results revealed a high use of IFID, offer of repair, and explanation. Although this might support the universality claim of speech acts strategies, it was clear that cultural norms and religion determined the choice of apology strategies significantly. This led to the discovery of new culture-specific strategies, as outlined later in this paper. This study gives an insight into politeness strategies in Libyan society, and it is hoped to contribute to the field of cross-cultural pragmatics.

Keywords: apologies, cross-cultural pragmatics, language and culture, Libyan Arabic, politeness, pragmatics, socio-pragmatics, speech acts

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Authors: Rawa Delshada, Sanaa G. Hamab, Rastee D. Koyeec

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Eighty patients with suspected ischemic heart disease were enrolled in the present study. They were classified into two groups: patients with positive exercise stress test results (n=40) and control group with negative exercise stress test results (n=40). Serum concentration of troponin I, Heart-type Fatty Acid Binding Protein (H-FABP) and Ischemia Modified Albumin (IMA) were measured one hour after performing stress test. Enzyme Linked Immunosorbent Assay was used to measure both troponin I, H-FABP levels, while IMA levels were measured by albumin cobalt binding test. There was no statistically significant difference in the mean concentration of troponin I between two groups (0.75±0.55ng/ml) for patients with positive test result vs. (0.71±0.55ng/ml) for negative test result group with P>0.05. Contrary to our expectation, mean IMA level was slightly higher among control group (70.88±39.76U/ml) compared to (62.7±51.9U/ml) in positive test result group, but still with no statistically significant difference (P>0.05). Median H-FABP level was also higher among negative exercise stress testing group compared the positive one (2ng/ml vs. 1.9ng/ml respectively), but failed to reach statistically significant difference (P>0.05). When quartiles model used to explore the possible association between each study biomarkers with the others; serum H-FABP level was lowest (1.7ng/ml) in highest quartile of IMA and lowest H-FABP (1.8ng/ml) in highest quartile of troponin I but with no statistically significant association (P>0.05). Myocardial ischemia, more likely occurred after exercise stress test, is not capable of causing troponin I release. Furthermore, an increase in H-FABP and IMA levels after stress test are not reflecting myocardial ischemia. Moreover, the combination of troponin I, H-FABP and IMA after measuring their post exercise levels does not improve the diagnostic utility of exercise stress test enormously.

Keywords: cardiac biomarkers, ischemic heart disease, troponin I, ischemia modified albumin, heart-type fatty acid binding protein, exercise stress testing

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Authors: Liaqat Ali, Hubert E. Blum, Türkân Sakinc

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Enterococcus faecium is an emerging multidrug-resistant nosocomial pathogen increased dramatically worldwide and causing bacteremia, endocarditis, urinary tract and surgical site infections in immunocomprised patients. The capsular polysaccharides that contribute to pathogenesis through evasion of the host innate immune system are also involved in hindering leukocyte killing of enterococci. The gene cluster (enterococcal polysaccharide antigen) of E. faecalis encoding homologues of many genes involved in polysaccharide biosynthesis. We identified two putative loci with 22 kb and 19 kb which contained 11 genes encoding for glycosyltransferases (GTFs); this was confirmed by using genome comparison of already sequenced strains that has no homology to known capsule genes and the epa-locus. The polysaccharide-conjugate vaccines have rapidly emerged as a suitable strategy to combat different pathogenic bacteria, therefore, we investigated a polysaccharide biosynthesis CapD protein in E. faecium contains 336 amino acids and had putative function for N-linked glycosylation. The deletion/knock-out capD mutant was constructed and complemented by homologues recombination method and confirmed by using PCR and sequencing. For further characterization and functional analysis, in-vitro cell culture and in-vivo a mouse infection models were used. Our ΔcapD mutant shows a strong hydrophobicity and all strains exhibited biofilm production. Subsequently, the opsonic activity was tested in an opsonophagocytic assay which shows increased in mutant compared complemented and wild type strains but more than two fold decreased in colonization and adherence was seen on surface of uroepithelial cells. However, a significant higher bacterial colonialization was observed in capD mutant during animal bacteremia infection. Unlike other polysaccharides biosynthesis proteins, CapD does not seems to be a major virulence factor in enterococci but further experiments and attention is needed to clarify its function, exact mechanism and involvement in pathogenesis of enteroccocal nosocomial infections eventually to develop a vaccine/ or targeted therapy.

Keywords: E. faecium, pathogenesis, polysaccharides, biofilm formation

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Authors: Mohammad Ahmad Ahmad Odah

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Aging is a complex biological process characterized by the progressive decline of physiological functions and increased vulnerability to age-related diseases. Epigenetic changes, particularly DNA methylation alterations, play a critical role in the aging process by influencing gene expression and genomic stability. This study explores the potential of epigenetic reprogramming as a strategy to reverse aging phenotypes in human fibroblasts. Using CRISPR-Cas9 gene editing and small molecule inhibitors targeting DNA methylation and histone acetylation, we successfully induced significant changes in DNA methylation and gene expression profiles. Our results demonstrate a global reduction in DNA methylation levels and the identification of differentially methylated regions (DMRs) associated with cellular senescence and DNA repair. Additionally, treated fibroblasts exhibited enhanced proliferative capacity, reduced cellular senescence, and improved differentiation potential. These findings suggest that epigenetic reprogramming could be a promising approach for regenerative medicine, offering potential therapeutic strategies to counteract age-related decline and extend healthy lifespan.

Keywords: epigenetic reprogramming, aging, regenerative medicine, DNA methylation, cellular rejuvenation, CRISPR-Cas9, senescence

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Authors: K. Benyounes, A. Benmounah

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Cement-based grouts has been used successfully to repair cracks in many concrete structures such as bridges, tunnels, buildings and to consolidate soils or rock foundations. In the present study, the rheological characterization of cement grout with water/binder ratio (W/B) is fixed at 0.5. The effect of the replacement of cement by bentonite (2 to 10 % wt) in presence of superplasticizer (0.5 % wt) was investigated. Several rheological tests were carried out by using controlled-stress rheometer equipped with vane geometry in temperature of 20°C. To highlight the influence of bentonite and superplasticizer on the rheological behavior of grout cement, various flow tests in a range of shear rate from 0 to 200 s-1 were observed. Cement grout showed a non-Newtonian viscosity behavior at all concentrations of bentonite. Three parameter model Herschel-Bulkley was chosen for fitting of experimental data. Based on the values of correlation coefficients of the estimated parameters, The Herschel-Bulkley law model well described the rheological behavior of the grouts. Test results showed that the dosage of bentonite increases the viscosity and yield stress of the system and introduces more thixotropy. While the addition of both bentonite and superplasticizer with cement grout improve significantly the fluidity and reduced the yield stress due to the action of dispersion of SP.

Keywords: rheology, cement grout, bentonite, superplasticizer, viscosity, yield stress

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Authors: Arash Sepehri Bonab

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Techniques to switch cells between development and differentiation, which tend to be commonly exclusive, are utilized in arrange to supply an expansive cell mass that can perform particular separated capacities required for the tissue to develop. Approaches to tissue engineering center on the have to give signals to cell populaces to advance cell multiplication and separation. Current tissue regenerative procedures depend primarily on tissue repair by transplantation of synthetic/natural inserts. In any case, restrictions on the existing procedures have expanded the request for tissue designing approaches. Tissue engineering innovation and stem cell investigation based on tissue building have made awesome advances in overcoming the issues of tissue and organ damage, useful loss, and surgical complications. Bone tissue has the capability to recover itself; in any case, surrenders of a basic estimate anticipate the bone from recovering and require extra support. The advancement of bone tissue building has been utilized to form useful options to recover the bone. This paper primarily portrays current advances in tissue engineering in different fields of bone and talks about the long-term trend of tissue designing innovation in the treatment of complex diseases.

Keywords: tissue engineering, bone, technologies, treatment

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Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei

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Limited research has examined the variations in dietary quality among U.S. adults diagnosed with chronic conditions like diabetes mellitus (DM), osteoarthritis (OA), and rheumatoid arthritis (RA), particularly across different age groups. Understanding how diet differs in relation to these conditions is crucial to developing targeted nutritional interventions. This cross-sectional study analyzed data from adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2021. Dietary quality was measured using the Healthy Eating Index (HEI)-2015 scores, encompassing both total and component scores for different dietary factors. Self-reported disease statuses for DM, OA, and RA were obtained, with age groups stratified into younger adults (20–59 years, n = 10,050) and older adults (60 years and older, n = 5,200). Logistic regression models, adjusted for demographic factors like sex, race/ethnicity, education, income, weight status, physical activity, and smoking, were used to examine the relationship between disease status and dietary quality, accounting for NHANES' complex survey design. Among younger adults, 8% had DM, 10% had OA, and 4% had RA. Among older adults, 22% had DM, 35% had OA, and 7% had RA. The results showed a consistent association between excess added sugar intake and DM in both age groups. In younger adults, excess sodium intake was also linked to DM, while low seafood and plant protein intake was associated with a higher prevalence of RA. Among older adults, a poor overall dietary pattern was strongly associated with RA, while OA showed varying associations depending on the intake of specific nutrients like fiber and saturated fats. The dietary quality of U.S. adults with DM, OA, and RA varies significantly by age group and disease type. Younger adults with these conditions demonstrated more specific dietary inadequacies, such as high sodium and low protein intake, while older adults exhibited a broader pattern of poor dietary quality, particularly in relation to RA. These findings suggest that personalized nutritional strategies are needed to address the unique dietary challenges faced by individuals with chronic conditions in different age groups.

Keywords: dietary, diabetes, osteoarthritis, rheumatoid arthritis, logistic regression

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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Authors: Matthew F. Gibson, Narasimha D. Rao, Raphael B. Slade, Joana Portugal Pereira, Joeri Rogelj

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Globally, India’s population is among the most severely impacted by nutrient deficiency, yet millions of tonnes of food are lost before reaching consumers. Across food groups, grains represent the largest share of daily calories and overall losses by mass in India. If current losses remain unresolved and follow projected population rates, we estimate, by 2030, losses from grains for human consumption could increase by 1.3-1.8 million tonnes (Mt) per year against current levels of ~10 Mt per year. This study quantifies energy input to minimise storage losses across India, responsible for a quarter of grain supply chain losses. In doing so, we identify and explore a Sustainable Development Goal (SDG) triplet between SDG₂, SDG₇, and SDG₁₂ and provide insight for development of joined up agriculture and health policy in the country. Analyzing rice, wheat, maize, bajra, and sorghum, we quantify one route to reduce losses in supply chains, by modelling the energy input to maintain favorable climatic conditions in modern silo storage. We quantify key nutrients (calories, protein, zinc, iron, vitamin A) contained within these losses and calculate roughly how much deficiency in these dietary components could be reduced if grain losses were eliminated. Our modelling indicates, with appropriate uncertainty, maize has the highest energy input intensity for storage, at 110 kWh per tonne of grain (kWh/t), and wheat the lowest (72 kWh/t). This energy trade-off represents 8%-16% of the energy input required in grain production. We estimate if grain losses across the supply chain were saved and targeted to India’s nutritionally deficient population, average protein deficiency could reduce by 46%, calorie by 27%, zinc by 26%, and iron by 11%. This study offers insight for development of Indian agriculture, food, and health policy by first quantifying and then presenting benefits and trade-offs of tackling food grain losses.

Keywords: energy, food loss, grain storage, hunger, India, sustainable development goal, SDG

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Authors: Mayowa Saheed Sanusi A, Musiliu Olushola Sunmonua, Abdulquadri Alakab Owolabi Raheema, Adeyemi Ikimot Adejokea

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The development of healthy cookies for health-conscious consumers cannot be overemphasized in the present global health crisis. This study was aimed to evaluate and model the influence of ripeness levels of papaya puree (unripe, ripe and overripe), oven temperature (130°C, 150°C and 170°C) and oven rack speed (stationary, 10 and 20 rpm) on physicochemical properties of papaya-based cookies using Response Surface Methodology (RSM). The physicochemical properties (baking time, cookies mass, cookies thickness, spread ratio, proximate composition, Calcium, Vitamin C and Total Phenolic Content) were determined using standard procedures. The data obtained were statistically analysed at p≤0.05 using ANOVA. The polynomial regression model of response surface methodology was used to model the physicochemical properties. The adequacy of the models was determined using the coefficient of determination (R²) and the response optimizer of RSM was used to determine the optimum physicochemical properties for the papaya-based cookies. Cookies produced from overripe papaya puree were observed to have the shortest baking time; ripe papaya puree favors cookies spread ratio, while the unripe papaya puree gives cookies with the highest mass and thickness. The highest crude protein content, fiber content, calcium content, Vitamin C and Total Phenolic Content (TPC) were observed in papaya based-cookies produced from overripe puree. The models for baking time, cookies mass, cookies thickness, spread ratio, moisture content, crude protein and TPC were significant, with R2 ranging from 0.73 – 0.95. The optimum condition for producing papaya based-cookies with desirable physicochemical properties was obtained at 149°C oven temperature, 17 rpm oven rack speed and with the use of overripe papaya puree. The Information on the use of puree from unripe, ripe and overripe papaya can help to increase the use of underutilized unripe or overripe papaya and also serve as a strategic means of obtaining a fat substitute to produce new products with lower production cost and health benefit.

Keywords: papaya based-cookies, modeling, response surface methodology, physicochemical properties

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Authors: Sairi Satari

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Introduction: Six-sigma is a metric that quantifies the performance of processes as a rate of Defects-Per-Million Opportunities. Sigma methodology can be applied in chemical pathology laboratory for evaluating process performance with evidence for process improvement in quality assurance program. In the laboratory, these methods have been used to improve the timeliness of troubleshooting, reduce the cost and frequency of quality control and minimize pre and post-analytical errors. Aim: The aim of this study is to evaluate the sigma values of the Cobas 8000 analyzer based on the minimum requirement of the specification. Methodology: Twenty-one analytes were chosen in this study. The analytes were alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), Amylase, aspartate transaminase (AST), total bilirubin, calcium, chloride, cholesterol, HDL-cholesterol, creatinine, creatinine kinase, glucose, lactate dehydrogenase (LDH), magnesium, potassium, protein, sodium, triglyceride, uric acid and urea. Total error was obtained from Clinical Laboratory Improvement Amendments (CLIA). The Bias was calculated from end cycle report of Royal College of Pathologists of Australasia (RCPA) cycle from July to December 2016 and coefficient variation (CV) from six-month internal quality control (IQC). The sigma was calculated based on the formula :Sigma = (Total Error - Bias) / CV. The analytical performance was evaluated based on the sigma, sigma > 6 is world class, sigma > 5 is excellent, sigma > 4 is good and sigma < 4 is satisfactory and sigma < 3 is poor performance. Results: Based on the calculation, we found that, 96% are world class (ALT, albumin, ALP, amylase, AST, total bilirubin, cholesterol, HDL-cholesterol, creatinine, creatinine kinase, glucose, LDH, magnesium, potassium, triglyceride and uric acid. 14% are excellent (calcium, protein and urea), and 10% ( chloride and sodium) require more frequent IQC performed per day. Conclusion: Based on this study, we found that IQC should be performed frequently for only Chloride and Sodium to ensure accurate and reliable analysis for patient management.

Keywords: sigma matrics, analytical performance, total error, bias

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Authors: Farida Eid, Hala Nasseif, Hana Mokhtar, Labib Riachi, Mudhar Hasan

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Bladder Endometriosis is a rare form of endometriosis and is defined as the presence of endometriotic tissue in the detrusor muscle of the bladder, either in full or partial thickness. Women typically present with dysuria, urinary frequency, hematuria, and recurrent urinary tract infections. Bladder endometriosis is typically found at the bladder base and bladder dome. Transvaginal ultrasound is considered first-line imaging, and the condition is typically managed with laparoscopic partial cystectomy. A 33-year-old nulliparous woman presented with chronic pelvic pain, severe dysmenorrhea, and metrorrhagia. The patient was previously diagnosed with bladder endometriomas two years ago with multiple recurrences. MRI revealed urinary bladder endometriosis measuring 3 x 2 x 1.5 cm. Accordingly, the patient underwent a cystoscopy-guided robotic-assisted excision of the endometriotic implant in the bladder with cystotomy and repair of the bladder mucosa. The operation was tolerated well, and the postoperative period was uneventful. Bladder Endometriosis (BE) typically presents with urinary symptoms and can be mistaken for a bladder tumor upon further imaging. The case was successfully managed with cystoscopy-guided, robotic-assisted excision and fulguration of the endometriotic implant in the bladder.

Keywords: endometriosis, bladder endometriosis (BE), urinary tract endometriosis (UTE), robotic-assisted surgery

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Authors: Khalil Aryanfar, Pariya Gholipor, Elmira Hafez

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This study examines the proportionality between the needs of industry and technical and vocational training of male and female vocational schools. The research method was descriptive that was conducted in two parts: documentary analysis and needs assessment and Delphi method was used in the need assessment. The statistical population of the study included 312 individuals from the industry sector employers and 52 of them were selected through stratified random sampling. Methods of data collection in this study, upstream documents include: document of the development of technical and vocational training, Statistical Yearbook 1393 in Tehran, the available documents in Isfahan Planning Department, the findings indicate that there is an almost proportionality between the needs of industry and Vocational training of male and female vocational schools in fields of welding, industrial electronics, electro technique, industrial drawing, auto mechanics, design, packaging, machine tool, metalworking, construction, accounting, computer graphics and the Administrative Affairs. The findings indicate that there is no proportionality between the needs of industry and Vocational training of male and female vocational schools in fields of Thermal - cooling systems, building electricity, building drawing, interior architecture, car electricity and motor repair.

Keywords: needs assessment, technical and vocational training, industry

Procedia PDF Downloads 454

Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

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Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

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Authors: Maryam Amiri Resketi, Sakineh Yeganeh, Khosro Jani Khalili

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The aim of this study was to investigate the effect of dietary lemon peel essential oil (Citrus limon) on serum parameters and liver enzyme activity of rainbow trout (Oncorhynchus mykiss) was exposed to deltamethrin. The 96-hour lethal concentrations of the toxin on rainbow trout (Oncorhynchus mykiss), was determined according to standard procedures O.E.C.D in static (Static). 96-hour LC50 was obtained 0.0082 mg/l by using statistical methods Probit program version. The maximum allowable concentration of deltamethrin was calculated 0.00082 mg/l in natural environment and was used for this experiment. Eight treatments were designed based on 3 levels of lemon essential oil 200, 400 and 600 mg/kg and 2 levels of deltamethrin 0 and 0.00082. Rainbow trout with an average weight of 95.14 ± 3.8 g were distributed in 300-liter tanks and cultured for eight weeks. Fish were fed in an amount of 2% of body weight. Water changes were done on a daily basis (90 percent of the tank). About the tanks containing 10 % deltamethrin, after dewatering, suitable concentration of toxin was added to water. At the end of the test, serum biochemical parameters (total protein, albumin, glucose, cholesterol, and triglycerides) and liver enzymes (ALP, AST, ALT and LDH) were evaluated. In treatments without and with toxin, increasing 400 mg/kg oil increased total protein and albumin levels and lower cholesterol and triglycerides were observed (p < 0.05). Rise to the level of 400 mg/kg of lemon peel essential oil treatments contain pesticides, reduced the amount of enzymes ALP, ALT and LDH compared to treatment of toxin-free lemon peel essential oil (p < 0.05). The results showed that usage of lemon peel essential oil in fish diet can increase the immune system parameters and strengthen it with strong antioxidant activity followed by reducing the effect of deltamethrin on the immune system of fish and effective dose can prevent the adverse effects of toxin due to the weakening of the fish immune system at the time of toxic pollutant entrance in fish farms.

Keywords: deltamethrin, Oncorhynchus mykiss, LC5096h, lemon peel (citrus limon) essential oil, serum parameters, liver enzymes

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Authors: Nizar Chaira

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Dates, main products of the oases, due to their therapeutic interests, are considered highly nutritious fruit. Several studies on the valuation biotechnology and technology of dates are made, and several products are already prepared. Isolation of the yeast Saccharomyces cerevisiae, naturally presents in a scrap of date, optimization of growth in the medium based on date syrup and production biomass can potentially expand the range of secondary products of dates. To this end, this paper tries to study the suitability for processing dates technology and biotechnology to use the date pulp as a carbon source for biological transformation. Two strains of Saccharomyces cerevisiae isolated from date syrup (S1, S2) and a commercial strain have used for this study. After optimization of culture conditions, production in a fermenter on two different media (date syrup and beet molasses) was performed. This is followed by studying the kinetics of growth, protein production and consumption of sugars in crops strain 1, 2 and the commercial strain and on both media. The results obtained showed that a concentration of 2% sugar, 2.5 g/l yeast extract, pH 4.5 and a temperature between 25 and 35°C are the optimal conditions for cultivation in a bioreactor. The exponential phase of the specific growth rate of a strain on both media showed that it is about 0.3625 h-1 for the production of a medium based on date syrup and 0.3521 h-1 on beet molasses with a generation time equal to 1.912 h and on the medium based on date syrup, yeast consumes preferentially the reducing sugars. For the production of protein, we showed that this latter presents an exponential phase when the medium starts to run out of reducing sugars. For strain 2, the specific growth rate is about 0.261h-1 for the production on a medium based on date syrup and 0207 h-1 on beet molasses and the base medium syrup date of the yeast consumes preferentially reducing sugars. For the invertase and other metabolits, these increases rapidly after exhaustion of reducing sugars. The comparison of productivity between the three strains on the medium based on date syrup showed that the maximum value is obtained with the second strain: p = 1072 g/l/h as it is about of 0923 g/l/h for strain 1 and 0644 g/l/h for the commercial strain. Thus, isolates of date syrup are more competitive than the commercial strain and can give the same performance in a shorter time with energy gain.

Keywords: date palm, fermentation, molasses, Saccharomyces, syrup

Procedia PDF Downloads 321

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

Procedia PDF Downloads 235

Authors: Danutė Jablonskytė-Raščė, Vidas Damanauskas

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The wheat (Triticum) genus is divided into many species, of which only two are widely distributed in the world - common wheat (Triticum aestivum L.) and durum wheat (Triticum durum Desf.). Common (soft) wheat is the most common type of wheat in the world and the most suitable for the harsh climate of Lithuania, but the grains have lower protein content and poorer nutritional properties. Durum wheat is characterized by a high protein content of the grain, but it is a crop of warmer climates grown in southern countries, Italy, Spain, the United States, Egypt, etc. Today's important issue is food, its resources and quality. The research focuses on healthier food grown in our conditions, the quality of which recently depends a lot not only on the cultivation technology but also on the warming climate conditions. Climatic conditions change the distribution of fungi and their hosts. Plants that have grown in our climate for many years have adapted to the use of fungicides, so the aim is to study cereal varieties grown in warmer climates and compare them with our country's varieties, studying their nutritional value and the spread of fungal diseases. The field experiments of different varieties of wheat were conducted at Joniškėlis Experimental Station of the Lithuanian Research Centre for Agriculture and Forestry in 2023. The soil of the experimental site was Endocalcari-Endohypogleyic Cambisol (CMg-n-w-can). The research was designed to identify the resistance to leaf diseases and the nutritional value of various wheat varieties. This research aims to focus on healthier food grown in our conditions, the quality of which recently depends a lot not only on the cultivation technology but also on the conditions of the warming climate. The study found that hot and humid summer weather led to the spread of foliar diseases in wheat. Tan spot (Pyrenophora tritici-repentis) is mostly spread in wheat crops. This disease had an average prevalence of 86.90%. The wheat crop was sparse, so this year was unfavorable for the spread of powdery mildew (Blumeria graminis). Dry weather prevailed during the period of flowering of cereals, which prevented the spread of ear diseases. Examining the qualitative indicators of grain, it was found that durum wheat had the best parameters.

Keywords: varieties, wheat, leaf disease, grain quality

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Authors: Raana Babadi Fathipour

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Nourishment nanotechnology is an range of rising intrigued and opens up a entirety universe of modern conceivable outcomes for the nourishment industry. The essential categories of nanotechnology applications and functionalities right now within the improvement of nourishment bundling incorporate: the enhancement of plastic materials obstructions, the consolidation of dynamic components that can convey utilitarian properties past those of customary dynamic bundling, and the detecting and signaling of significant data. Nano nourishment bundling materials may amplify nourishment life, move forward nourishment security, alarm buyers that nourishment is sullied or ruined, repair tears in bundling, and indeed release preservatives to expand the life of the nourishment within the bundle. Nanotechnology applications within the nourishment industry can be utilized to identify microbes in bundling, or produce stronger flavors and color quality, and security by expanding the obstruction properties. Nanotechnology holds extraordinary guarantee to supply benefits not fair inside nourishment items but too around nourishment items. In reality, nanotechnology presents modern chances for advancement within the nourishment industry at monstrous speed, but instability and wellbeing concerns are moreover developing. EU/WE/global enactment for the direction of nanotechnology in nourishment are scanty. Besides, current enactment shows up unacceptable to nanotechnology specificity.

Keywords: nano technology, nano foods, food packaging, nano participle

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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

Procedia PDF Downloads 380

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Duong Thuy Nguyen, Giulia Bencini

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The present study examined structural and prosodic factors on the computation of antecedent-reflexive relationships and sentence comprehension in native English (L1) and Vietnamese-English bilinguals (L2). Participants read sentences presented on the computer screen in one of three presentation formats aimed at manipulating prosodic parsing: word-by-word (RSVP), phrase-segment (self-paced), or whole-sentence (self-paced), then completed a grammaticality rating and a comprehension task (following Pratt & Fernandez, 2016). The design crossed three factors: syntactic structure (simple; complex), grammaticality (target-match; target-mismatch) and presentation format. An example item is provided in (1): (1) The actress that (Mary/John) interviewed at the awards ceremony (about two years ago/organized outside the theater) described (herself/himself) as an extreme workaholic). Results showed that overall, both L1 and L2 speakers made use of a good-enough processing strategy at the expense of more detailed syntactic analyses. L1 and L2 speakers’ comprehension and grammaticality judgements were negatively affected by the most prosodically disrupting condition (word-by-word). However, the two groups demonstrated differences in their performance in the other two reading conditions. For L1 speakers, the whole-sentence and the phrase-segment formats were both facilitative in the grammaticality rating and comprehension tasks; for L2, compared with the whole-sentence condition, the phrase-segment paradigm did not significantly improve accuracy or comprehension. These findings are consistent with the findings of Pratt & Fernandez (2016), who found a similar pattern of results in the processing of subject-verb agreement relations using the same experimental paradigm and prosodic manipulation with English L1 and L2 English-Spanish speakers. The results provide further support for a Good-Enough cue model of sentence processing that integrates cue-based retrieval and implicit prosodic parsing (Pratt & Fernandez, 2016) and highlights similarities and differences between L1 and L2 sentence processing and comprehension.

Keywords: anaphora resolution, bilingualism, implicit prosody, sentence processing

Procedia PDF Downloads 152