Search results for: protein kinase C alpha

Authors: Mustafa Al-Yaseen, Haider Mohammed Mahdi, Haider Ali Al–Zahid, Nazar S. Haddad

Abstract:

Background: Early diagnosis of musculoskeletal infections is of vital importance to avoid devastating complications. There is no single laboratory marker which is sensitive and specific in diagnosing these infections accurately. White blood cell count, erythrocyte sedimentation rate, and C-reactive protein are not specific as they can also be elevated in conditions other than bacterial infections. Materials Culture and sensitivity is not a true gold standard due to its varied positivity rates. Serum Procalcitonin is one of the new laboratory markers for pyogenic infections. The objective of this study is to assess the value of PCT in the diagnosis of soft tissue, bone, and joint infections. Patients and Methods: Patients of all age groups (seventy-four patients) with a diagnosis of musculoskeletal infection are prospectively included in this study. All patients were subjected to White blood cell count, erythrocyte sedimentation rate, C-reactive protein, and serum Procalcitonin measurements. A healthy non infected outpatient group (twenty-two patients) taken as a control group and underwent the same evaluation steps as the study group. Results: The study group showed mean Procalcitonin levels of 1.3 ng/ml. Procalcitonin, at 0.5 ng/ml, was (42.6%) sensitive and (95.5%) specific in diagnosing of musculoskeletal infections with (positive predictive value of 87.5% and negative predictive value of 48.3%) and (positive likelihood ratio of 9.3 and negative likelihood ratio of 0.6). Conclusion: Serum Procalcitonin, at a cut – off of 0.5 ng/ml, is a specific but not sensitive marker in the diagnosis of musculoskeletal infections, and it can be used effectively to rule in the diagnosis of infection but not to rule out it.

Keywords: procalcitonin, infection, labratory markers, musculoskeletal

Procedia PDF Downloads 163

Authors: M. Ntswane, N. Mbuma, M. Labuschagne, A. Mofokeng, M. Rantso

Abstract:

Cowpea is an essential legume for the nutrition and health of millions of people in different regions. The production and productivity of the crop are very limited in South Africa due to a lack of adapted and stable genotypes. The improvement of nutritional quality is made possible by manipulating the genes of diverse cowpea genotypes available around the world. Assessing the adaptability and stability of the cowpea mutant genotypes for yield and nutritional quality requires examining them in different environments. The objective of the study was to determine the adaptability and stability of cowpea mutant genotypes under South African conditions and to identify the superior genotypes that combine grain yield components, antioxidants, and nutritional quality. Thirty-one cowpea genotypes were obtained from the Agricultural Research Council grain crops (ARC-GC) and were planted in Glen, Mafikeng, Polokwane, Potchefstroom, Taung, and Vaalharts during the 2021/22 summer cropping season. Significant genotype by location interactions indicated the possibility of genetic improvement of these traits. The genotype plus genotype by environment indicated broad adaptability and stability of mutant genotypes. The principal component analysis identified the association of the genotypes with the traits. Phenotypic correlation analysis showed that Zn and protein content were significant and positively correlated and suggested the possibility of indirect selection of these traits. Results from this study could be used to help plant breeders in making informed decisions and developing nutritionally improved cowpea genotypes with the aim of addressing the challenges of poor nutritional quality.

Keywords: cowpea seeds, adaptability, stability, mineral elements, protein content

Procedia PDF Downloads 116

Authors: Maricarmen Herrera, Pierre Chymkowitch, Joe Robertson, Jens Eriksson, Jorrit Enserink

Abstract:

tRNA genes are transcribed by RNA polymerase III. During recent years, it has become clear that tDNA transcription fluctuates during the cell cycle. However, the mechanism by which the cell cycle controls the amplitude of tDNA transcription remains unknown. We found that the cyclin Clb5 recruits the cyclin dependent kinase Cdk1 to tRNA genes to sharply increase tRNA synthesis during a brief interval in the cell cycle. We show that Cdk1 promotes the interaction of TFIIIB with TFIIIC, that it stimulates the recruitment of TFIIIC to tRNA genes, that it prevents the formation of an overly stable TFIIIB-tDNA complex and that it augments the dynamics of RNA polymerase III. Furthermore, we identify Bdp1 as a novel Cdk1 substrate, and phosphorylation of Bdp1 is required for the cell cycle-dependent increase in tDNA transcription. In addition, we show that phosphorylation of the Cdk1 substrate Nup60 mediates formation of a Nup60-Nup2 complex at tRNA genes, which is also required for cell cycle-dependent tDNA transcription. Together, our findings indicate that Cdk1 activity gates tRNA synthesis by regulating the dynamics of the TFIIIB-TFIIIC-RNAPIII complex, and that it may promote the formation of a nuclear pore microenvironment conducive to efficient tDNA transcription.

Keywords: Cdk1, cell cycle, RNAPIII machinery, tRNA

Procedia PDF Downloads 182

Authors: Alia Aldarmaki, Ahmad Elshennawy

Abstract:

There is a global shift in healthcare systems’ emphasizing engaging different stakeholders in selecting quality improvement initiatives and incorporating their preferences to improve the healthcare efficiency and outcomes. Although experts bring scientific knowledge based on the scientific model and their personal experience, other stakeholders can bring new insights and information into the decision-making process. This study attempts to explore the impact of incorporating different stakeholders’ preference in identifying the most significant criteria that should be considered in healthcare for electing the improvement projects. A Framework based on a modified Fuzzy Delphi Method (FDM) was built. In addition to, the subject matter experts, doctors/physicians, nurses, administrators, and managers groups contribute to the selection process. The research identifies potential criteria for evaluating projects in healthcare, then utilizes FDM to capture expertise knowledge. The first round in FDM is intended to validate the identified list of criteria from experts; which includes collecting additional criteria from experts that the literature might have overlooked. When an acceptable level of consensus has been reached, a second round is conducted to obtain experts’ and other related stakeholders’ opinions on the appropriate weight of each criterion’s importance using linguistic variables. FDM analyses eliminate or retain the criteria to produce a final list of the critical criteria to select improvement projects in healthcare. Finally, reliability and validity were investigated using Cronbach’s alpha and factor analysis, respectively. Two case studies were carried out in a public hospital in the United Arab Emirates to test the framework. Both cases demonstrate that even though there were common criteria between the experts and the stakeholders, still stakeholders’ perceptions bring additional critical criteria into the evaluation process, which can impact the outcomes. Experts selected criteria related to strategical and managerial aspects, while the other participants preferred criteria related to social aspects such as health and safety and patients’ satisfaction. The health and safety criterion had the highest important weight in both cases. The analysis showed that Cronbach’s alpha value is 0.977 and all criteria have factor loading greater than 0.3. In conclusion, the inclusion of stakeholders’ perspectives is intended to enhance stakeholders’ engagement, improve transparency throughout the decision process, and take robust decisions.

Keywords: Fuzzy Delphi Method, fuzzy number, healthcare, stakeholders

Procedia PDF Downloads 129

Authors: Richard Pincak

Abstract:

Starting from a 4D spacetime model using a partially negative dimensional product manifold (PNDP-manifold), which emerges as a 2D spacetime, we developed an analysis of tidal forces and Hawking radiation near the event horizon of a Schwarzchild black hole. The modified 2D metric, incorporating the effects of the four-dimensional Weyl tensor, with the dilatonic field and the newly derived time relation \(2\alpha t = \ln \epsilon\), can enable a deeper understanding of quantum gravity. The analysis shows how the modified Hawking temperature and distribution of emitted particles are affected by additional fields, providing potential observables for future experiments.

Keywords: black holes, Hawking radiation, Weyl tensor, information paradox

Procedia PDF Downloads 22

Authors: Temitope D. Awobusuyi, Eric O. Amonsou, Muthulisi Siwela

Abstract:

Amahewu, a lactic acid fermented non-alcoholic maize based beverage is widely consumed in Southern Africa. It is traditionally made with white maize which is deficient in vitamin A. Provitamin A-biofortified maize has been developed for use as a complementary strategy to alleviate vitamin A deficiency. In this study the nutritional composition and protein digestibility of amahewu produced using provitamin A-biofortified maize was determined. Provitamin A-biofortified amahewu was processed by fermenting cooked maize porridge using malted provitamin A-biofortified maize, wheat bran and lactobacillus mixed starter culture with either malted maize or wheat bran. The total provitamin A content in amahewu products ranged from 3.3-3.8 μg/g (DW). The % retention of total provitamin A ranged from 79 %- 90 % μg/g (DW). The lowest % retention was observed in products fermented with the addition of starter culture. The gross energy of amahewu products were approx. 20 MJ/kg. There was a slight increase in the lysine content of amahewu after fermentation. Protein digestibility of amahewu (approx.91%) was slightly higher compared to unprocessed provitamin A maize (86%). However, a general decrease was observed in the minerals when compared to the unprocessed provitamin A maize. Amahewu processed using starter cultures has higher iron content than those processed with the addition of malt. These result suggests that provitamin A-biofortified amahewu has the potential to make a significant contribution towards alleviating Vitamin A Deficiency in rural communities who are also the most vulnerable to VAD.

Keywords: vitamin A deficiency, provitamin A maize, biofortification, fermentation

Procedia PDF Downloads 418

Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa

Abstract:

This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.

Keywords: C. sinensis, function indices, harvest time, leaf essential oil.

Procedia PDF Downloads 360

Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki

Abstract:

Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.

Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism

Procedia PDF Downloads 180

Authors: Mahsa Jalili, Trude Johansen, Signe Dille Lovmo, Turid Rustad, Rolf Erik Olsen, Atle M. Bones

Abstract:

The quality of fish muscle is a key factor in fish industry, and dietary ingredients can influence fish quality. The aim of this study was to examine the impact of krill meal, soybean meal, Bactocell® and butyrate fortified feeds and control diet on characteristics of salmon fillet. Thirty Atlantic salmon (6 per each group) were farmed for 12 weeks. All the fish were killed and frozen immediately. The white muscle from top posterior part of dorsal fin was dissected to analyze fat content, carotenoid content, content of water-soluble and salt-soluble proteins, cathepsin B and cathepsin B-L activities. ANOVA test was used to analyze mean and standard error of mean values at 0.05 significance level. There were significant difference in cathepsin B activity, water-soluble proteins and salt-soluble proteins (p-value= 0.005, 0.009 and 0.002). The mean values of other factors were not significantly different among the groups. Cathepsin B activity was higher in soymeal group. Water-soluble proteins were reported higher in soy meal and krill groups and salt-soluble proteins were significantly higher in soy meal and butyrate rich diets. Although soy meal has proven effect on enteritis, it results in higher percentage of protein in fillets. On the other hand, this feeding may have role in textural deterioration of fillets owing to higher values of endogenous cathepsin B in soymeal group.

Keywords: aquaculture, food quality, Krill protein extract, prebiotics, probiotics, Salmo salar, soy

Procedia PDF Downloads 210

Authors: Abeer Rababa'h, Ragad Bsoul, Mohammad Alkhatatbeh, Karem Alzoubi

Abstract:

Introduction: Tobacco use is one of the main risk factors to cardiovascular diseases (CVD) and atherosclerosis in particular. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. Therefore, the aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long-term (8 weeks) exposures. Methods: mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin-1 (ET-1) and, myeloperoxidase (MPO). Following protein estimation, enzyme-linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET-1 protein expressions. Results: our data showed that acute exposure to WPS significantly enhances the levels of MMP-3, MMP- 9, and MPO expressions (p < 0.05) compared to their corresponding control. However, the body was capable to normalize the level of expressions for such parameters following continuous exposure for 8 weeks (p > 0.05). Additionally, we showed that the level of ET-1 expression was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p < 0.05). Conclusion: Waterpipe exposure has a significant negative effect on atherosclerosis and the enhancement of the atherosclerotic biomarkers expression (MMP-3 and 9, MPO, and ET-1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.

Keywords: atherosclerotic biomarkers, cardiovascular disease, matrix metalloproteinase, waterpipe

Procedia PDF Downloads 354

Authors: Mark-Adam Kellerman

Abstract:

Proteins are capable of exploring vast mutational spaces. This makes it difficult for protein engineers to devise rational methods to improve stability and function via mutagenesis. Deciding which residues to mutate requires knowledge of the characteristics they elicit. We probed the characteristics of residues in granulocyte-colony stimulating factor (G-CSF) using a thermal melt (from 295K to 323K) to denature it in a 700 MHz Bruker spectrometer. These characteristics included dynamics, micro-environmental changes experienced/ induced during denaturing and structure-function relationships. 15N-1H HSQC experiments were performed at 2K increments along with this thermal melt. We observed that dynamic residues that also undergo a lot of change in their microenvironment were predominantly in unstructured regions. Moreover, we were able to identify four residues (G4, A6, T133 and Q134) that we class as high priority targets for mutagenesis, given that they all appear in both the top 10% of measures for environmental changes and dynamics (∑Δ and ∆PI). We were also able to probe these NMR observables and combine them with molecular dynamics (MD) to elucidate what appears to be an opening motion of G-CSFs binding site III. V48 appears to be pivotal to this opening motion, which also seemingly distorts the loop region between helices A and B. This observation is in agreement with previous findings that the conformation of this loop region becomes altered in an aggregation-prone state of G-CSF. Hence, we present here an approach to profile the characteristics of residues in order to highlight their potential as rational mutagenesis targets and their roles in important conformational changes. These findings present not only an opportunity to effectively make biobetters, but also open up the possibility to further understand epistasis and machine learn residue behaviours.

Keywords: protein engineering, rational mutagenesis, NMR, molecular dynamics

Procedia PDF Downloads 255

Authors: Samira Khalaji, , Fenneke Klein Jan, Kay-E. Gottschalk, Eugenia Makrantonaki, Karin Scharffetter-Kochanek

Abstract:

Biological aging is a multi-dimensional process that takes place over a whole range of scales from the nanoscopic alterations within individual cells, over transformations in tissues and organs and to changes of the whole organism. On the single cell level, aging involves mutation of genes, differences in gene expression levels as well as altered posttranslational modifications of proteins. A variety of proteins is affected, including proteins of the cell cytoskeleton and migration machinery. Previous work quantified the expression of cytoskeleton proteins on the gene and protein levels in senescent and young fibroblasts. Their results show that senescent skin fibroblasts have an upregulated expression of the intermediate filament (IF) protein vimentin in contrast to actin and tubulin, which are downregulated. IFs play an important role in providing mechanical stability of cells. However, the mechanical properties of IFs depending on cellular senescence or age of the donor has not been studied so far. Hence, we employed passive microrheology on primary human dermal fibroblasts from female donors with age of 28 years (young) and 86 years (old) as model of in vivo aging and human normal dermal fibroblast from 11-year old male with CPD 17-35 (young) and CPD 58-59 (senescence) as a model of in vitro replicative senescence. In contrast to the expectations, our primary results show no significant differences in the viscoelastic properties of fibroblasts depending on age of the donor or cellular replicative senescence.

Keywords: aging, cytoskeleton, fibroblast, mechanical properties

Procedia PDF Downloads 322

Authors: Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Amornnat Thuppia, Nuntiya Somparn

Abstract:

Several dietary and herbal plants have been shown to possess cytoprotective and antioxidant effects with various mechanisms of action. The aim of this study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Ocimum americanum (OA), commonly known as American basil or 'hoary basil', in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 100, 200 and 400 mg/kg for 28 days. Phytochemical screening of plant extracts revealed the presence of alkaloid, cardiac glycosides, tannin and steroid compounds. The extract contained phenolic compounds 36.91 ± 0.66 mg of gallic acid equivalents per gram OA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 41.27 ± 1.86 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. The protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased compared with normal control. Consistent with the induction of γ-GCL protein expression significantly reduction of serum oxidative stress marker malondialdehyde (MDA) was found in rat treated with OA extract compared with control. Taken together, this study provides evidence that Ocimum americanum exhibits direct antioxidant properties and can induce cytoprotective enzyme in vivo.

Keywords: antioxidant, γ-glutamylcysteine ligase, MDA, Ocimum americanum

Procedia PDF Downloads 246

Authors: H. Nagendra, Vinod Kumar, S. Mukherjee

Abstract:

In this study, the potential benefits of playing action video game among congenitally deaf and dumb subjects is reported in terms of EEG ratio indices. The frontal and occipital lobes are associated with development of motor skills, cognition, and visual information processing and color recognition. The sixteen hours of First-Person shooter action video game play resulted in the increase of the ratios β/(α+θ) and β/θ in frontal and occipital lobes. This can be attributed to the enhancement of certain aspect of cognition among deaf and dumb subjects.

Keywords: cognitive enhancement, video games, EEG band powers, deaf and dumb subjects

Procedia PDF Downloads 436

Authors: Arefeh Jafarian, Mohammad Taghikani, Saied Abroun, Amir Allahverdi, Masoud Soleimani

Abstract:

Introduction: The miRNAs have key roles in control of pancreatic islet development and insulin secretion. In this regards, current study investigated the pancreatic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) by up-regulation of miR-375 and down-regulation of miR-9 by lentiviruses containing miR-375 and anti-miR-9. Findings: After 21 days of induction, islet-like clusters containing insulin producing cells (IPCs) were confirmed by dithizone (DTZ) staining. The IPCs and β cell specific related genes and proteins were detected using qRT-PCR and immunofluorescence on days 7, 14 and 21 of differentiation. Glucose challenge test was performed at different concentrations of glucose as well as extracellular and intracellular insulin and C-peptide were assayed using ELISA kit. In derived IPCs by miR-375 alone are capable to express insulin and other endocrine specific transcription factors, the cells lack the machinery to respond to glucose. The differentiated hMSCs by miR-375 and anti-miR-9 lentiviruses could secrete insulin and c-peptide in a glucose-regulated manner. Conclusion: It was found that over-expression of miR-375 led to a reduction in levels of Mtpn protein in derived IPCs, while treatment with anti-miR-9 following miR-375 over-expression had synergistic effects on MSCs differentiation and insulin secretion in a glucose-regulated manner. The researchers reported that silencing of miR-9 increased OC-2 protein in IPCs that may contribute to the observed glucose-regulated insulin secretion. These findings highlight miRNAs functions in stem cells differentiation and suggest that they could be used as therapeutic tools for gene-based therapy in diabetes mellitus.

Keywords: diabetes, differentiation, MSCs, insulin producing cells, miR-375, miR-9

Procedia PDF Downloads 317

Authors: Vrushali Guhe, Shailza Singh

Abstract:

Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

Procedia PDF Downloads 84

Authors: Vatsal M. Patel, Navin B. Patel

Abstract:

The present studies deal with the developing a series bearing a diphenyl ethers nucleus using structure-based drug design concept. A newer series of diphenyl ether based azetidinone namely N-(3-chloro-2-oxo-4-(3-phenoxyphenyl)azetidin-1-yl)-2-(substituted amino)acetamide (2a-j) have been synthesized by condensation of m-phenoxybenzaldehyde with 2-(substituted-phenylamino)acetohydrazide followed by the cyclisation of resulting Schiff base (1a-j) by conventional method as well as microwave heating approach as a part of an environmentally benign synthetic protocol. All the synthesized compounds were characterized by spectral analysis and were screened for in vitro antimicrobial, antitubercular and antiprotozoal activity. The compound 2f was found to be most active M. tuberculosis (6.25 µM) MIC value in the primary screening as well as this same derivative has been found potency against L. mexicana and T. cruzi with MIC value 2.09 and 6.69 µM comparable to the reference drug Miltefosina and Nifurtimox. To provide understandable evidence to predict binding mode and approximate binding energy of a compound to a target in the terms of ligand-protein interaction, all synthesized compounds were docked against an enoyl-[acyl-carrier-protein] reductase of M. tuberculosis (PDB ID: 4u0j). The computational studies revealed that azetidinone derivatives have a high affinity for the active site of enzyme which provides a strong platform for new structure-based design efforts. The Lipinski’s parameters showed good drug-like properties and can be developed as an oral drug candidate.

Keywords: antimycobacterial, antiprotozoal, azetidinone, diphenylether, docking, microwave

Procedia PDF Downloads 162

Authors: Disaphon Boobpachat, Nuttaset Manimmanakorn, Apiwan Manimmanakorn, Worrawut Thuwakum, Michael J. Hamlin

Abstract:

Objectives: To evaluate effect of kinesio tape compared to placebo tape and static stretching on recovery of anaerobic power and maximal oxygen uptake (Vo₂max) after intensive exercise. Methods: Thirty nine untrained healthy volunteers were randomized to 3 groups for each intervention: elastic tape, placebo tape and stretching. The participants performed intensive exercise on the dominant quadriceps by using isokinetic dynamometry machine. The recovery process was evaluated by creatine kinase (CK), pressure pain threshold (PPT), muscle soreness scale (MSS), maximum voluntary contraction (MVC), jump height, anaerobic power and Vo₂max at baseline, immediately post-exercise and post-exercise day 1, 2, 3 and 7. Results: The kinesio tape, placebo tape and stretching groups had significant changes of PPT, MVC, jump height at immediately post-exercise compared to baseline (p < 0.05), and changes of MSS, CK, anaerobic power and Vo₂max at day 1 post-exercise compared to baseline (p < 0.05). There was no significant difference of those outcomes among three groups. Additionally, all experimental groups had little effects on anaerobic power and Vo₂max compared to baseline and compared among three groups (p > 0.05). Conclusion: Kinesio tape and stretching did not improve recovery of anaerobic power and Vo₂max after eccentric exercise compared to placebo tape.

Keywords: stretching, eccentric exercise, Wingate test, muscle soreness

Procedia PDF Downloads 130

Authors: Pablo Martin, Jorge Olivares, Fernando Maass

Abstract:

The use of fractional derivatives to different problems in Engineering and Physics has been increasing in the last decade. For this reason, we have here considered partial derivatives when the integral is a spherical Bessel function of the first kind in both regular and modified ones simple initial conditions have been also considered. In this way, the solution has been found as a combination of hypergeometric functions. The case of a general rational value for α of the fractional derivative α has been solved in a general way for alpha between zero and two. The modified spherical Bessel functions of the first kind have been also considered and how to go from the regular case to the modified one will be also shown.

Keywords: caputo fractional derivatives, hypergeometric functions, linear differential equations, spherical Bessel functions

Procedia PDF Downloads 328

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

Abstract:

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

Procedia PDF Downloads 358

Authors: Sh. Hamada

Abstract:

The current work aims to study the rainbow like-structure observed in the elastic scattering of alpha particles on both ¹²C and ¹⁶O nuclei. We reanalyzed the experimental elastic scattering angular distributions data for α+¹²C and α+¹⁶O nuclear systems at different energies using both optical model and double folding potential of different interaction models such as: CDM3Y1, DDM3Y1, CDM3Y6 and BDM3Y1. Potential created by BDM3Y1 interaction model has the shallowest depth which reflects the necessity to use higher renormalization factor (N_r). Both optical model and double folding potential of different interaction models fairly reproduce the experimental data.

Keywords: density distribution, double folding, elastic scattering, nuclear rainbow, optical model

Procedia PDF Downloads 237

Authors: A. G. Miah, U. Salma, K. Schellander

Abstract:

Relaxin was first described in 1926 by Frederick Hisaw. Previously it was considered as only the hormone of pregnant mammals due to its important roles in pregnancy and parturition. From the last decade, the physiological role of relaxin in male reproduction has been given experimental attention, and the results have made it clear that relaxin can no longer be considered strictly as only the hormone of female reproduction. The accessory glands (specially, the prostate glands) of the male reproductive system are the source of seminal relaxin, which is secreted into the seminal plasma and saturated with spermatozoa just after ejaculation. Several studies have reported that relaxin has important roles in improving motility in human sperm. Thereafter, the growing interest on relaxin has intensified efforts to investigate the role of relaxin in other sperm physiological phenomena like, capacitation, acrosome reaction, and their mediating factors associated with successful fertilization. Therefore, this review aims to provide up-to-date information about the physiological roles of relaxin in sperm motility, capacitation, acrosome reaction, and their mediating factors, such as, utilization of glucose, cholesterol efflux, Ca2+-influx, intracellular cAMP and protein tyrosine phosphorylation. Some studies have shown relaxin to increase the percentage of progressive motility and induce capacitation and acrosome reaction through increasing the utilization of glucose and mediating the cholesterol efflux, Ca2+-influx, intracellular cAMP and protein tyrosine phosphorylation. Thus, the review suggests that the supplementation of relaxin into the capacitating medium may contribute the possible beneficial roles in fresh and cryopreserved spermatozoal prefertilization events.

Keywords: relaxin, physiological roles, prefertilizing activities, spermatozoa

Procedia PDF Downloads 569

Authors: Aida Kalantari, Boyang Ji, Tao Chen, Ivan Mijakovic

Abstract:

3-hydroxypropanoic acid (3-HP) is one of the most important biomass-derivable platform chemicals that can be converted into a number of industrially important compounds. There have been several attempts at production of 3-HP from renewable sources in cell factories, focusing mainly on Escherichia coli, Klebsiella pneumoniae, and Saccharomyces cerevisiae. Despite the significant progress made in this field, commercially exploitable large-scale production of 3-HP in microbial strains has still not been achieved. In this study, we investigated the potential of Bacillus subtilis to be used as a microbial platform for bioconversion of glycerol into 3-HP. Our recombinant B. subtilis strains overexpress the two-step heterologous pathway containing glycerol dehydratase and aldehyde dehydrogenase from various backgrounds. The recombinant strains harboring the codon-optimized synthetic pathway from K. pneumoniae produced low levels of 3-HP. Since the enzymes in the heterologous pathway are sensitive to oxygen, we had to perform our experiments in micro-aerobic conditions. Under these conditions, the cell produces lactate in order to regenerate NAD+, and we found the lactate production to be in competition with the production of 3-HP. Therefore, based on the in silico predictions, we knocked out the glycerol kinase (glpk), which in combination with growth on glucose, resulted in improving the 3-HP titer to 1 g/L and the removal of lactate. Cultivation of the same strain in an enriched medium improved the 3-HP titer up to 7.6 g/L. Our findings provide the first report of successful introduction of the biosynthetic pathway for conversion of glycerol into 3-HP in B. subtilis.

Keywords: bacillus subtilis, glycerol, 3-hydroxypropanoic acid, metabolic engineering

Procedia PDF Downloads 248

Authors: Gladys Abiemwense Ibhaze, Anthony Henry Ekeocha, Adebowale Noah Fajemisin, Tope Oke, Caroline Tosin Alade,

Abstract:

The study was conducted to evaluate the silage quality and acceptability of ensiled avocado pear skin (APS) with cassava peel (CSP) and brewers’ grain (BG) using eighteen (18) West African Dwarf goats with an average weight of 7.0±1.5 kg. The experimental diets; 1) 50% cassava peel+ 50% brewers’ grain, 2) 50% brewers’ grain+ 50% avocado pear skin, 3) 50% cassava peel +25% brewers’ grain+ 25% avocado pear skin were ensiled for 21 days. The experimental design was a completely randomized design (CRD). The chemical composition of the diets was investigated. The acceptability of the diets was evaluated for twelve (12) days. Results obtained showed that the crude protein content ranged from 12.18 – 12.47%, crude fiber (15.99-22.67%). Results obtained showed that diet 1 had the least pH value (4.0), followed by diet 3 (4.5) and diet 2 (5.2). All diets were firm in texture and maintained their initial color. The temperature ranged from 27-29 ⁰C with diet 2 having the highest temperature of 29 ⁰C. Acceptability of experimental diets varied (p < 0.05) significantly. Dry matter intake ranged from (426.22-686.73g/day) with animals on a diet one recording the highest dry matter intake. The coefficient of preference and percentage preference, also differed (p <0.05) significantly among the diets. Diet 1 had a coefficient of preference greater than unity. However, this was not significantly (p>0.05) different from diet two but differed from diet 3. Conclusively, APS could be included in goats’ diets in the absence of CSP during feed scarcity provided a rich source of protein is available.

Keywords: avocado pear skin, Brewers' grain, Cassava peel, preference

Procedia PDF Downloads 204

Authors: Oseyemi Omowunmi Olubomehin, Olufemi Michael Denton

Abstract:

Diabetes mellitus is a disease that is related to the digestion of carbohydrates, proteins and fats and how this affects the blood glucose levels. Various synthetic drugs employed in the management of the disease work through different mechanisms. Keeping postprandial blood glucose levels within acceptable range is a major factor in the management of type 2 diabetes and its complications. Thus, the inhibition of carbohydrate-hydrolyzing enzymes such as α-amylase is an important strategy in lowering postprandial blood glucose levels, but synthetic inhibitors have undesirable side effects like flatulence, diarrhea, gastrointestinal disorders to mention a few. Therefore, it is necessary to identify and explore the α-amylase inhibitors from plants due to their availability, safety, and low costs. In the present study, extracts from the leaves of Rauvolfia vomitoria and seeds of Picralima nitida which are used in the Nigeria traditional system of medicine to treat diabetes were tested for their α-amylase inhibitory effect. The powdered plant samples were subjected to phytochemical screening using standard procedures. The leaves and seeds macerated successively using n-hexane, ethyl acetate and methanol resulted in the crude extracts which at different concentrations (0.1, 0.5 and 1 mg/mL) alongside the standard drug acarbose, were subjected to α-amylase inhibitory assay using the Benfield and Miller methods, with slight modification. Statistical analysis was done using ANOVA, SPSS version 2.0. The phytochemical screening results of the leaves of Rauvolfia vomitoria and the seeds of Picralima nitida showed the presence of alkaloids, tannins, saponins and cardiac glycosides while in addition Rauvolfia vomitoria had phenols and Picralima nitida had terpenoids. The α-amylase assay results revealed that at 1 mg/mL the methanol, hexane, and ethyl acetate extracts of the leaves of Rauvolfia vomitoria gave (15.74, 23.13 and 26.36 %) α-amylase inhibitions respectively, the seeds of Picralima nitida gave (15.50, 30.68, 36.72 %) inhibitions which were not significantly different from the control at p < 0.05, while acarbose gave a significant 56 % inhibition at p < 0.05. The presence of alkaloids, phenols, tannins, steroids, saponins, cardiac glycosides and terpenoids in these plants are responsible for the observed anti-diabetic activity. However, the low percentages of α-amylase inhibition by these plant samples shows that α-amylase inhibition is not the major way by which both plants exhibit their anti-diabetic effect.

Keywords: alpha-amylase, Picralima nitida, postprandial hyperglycemia, Rauvolfia vomitoria

Procedia PDF Downloads 192

Authors: I. Karagjozova, B. Dejanova, J. Pluncevic, S. Petrovska, V. Antevska, L. Todorovska

Abstract:

Introduction: Medical checking assessment is important in sports medicine. To follow the health condition in subjects who perform sports, body composition parameters, such as intracellular water, extracellular water, protein and mineral content, muscle and fat mass might be useful. The aim of the study was to show available parameters and to compare them to manual assessment. Material and methods: A number of 20 subjects (14 male and 6 female) at age of 20±2 years were determined in the study, 5 performed recreational sports, while others were professional ones. The mean height was 175±7 cm, the mean weight was 72±9 cm, and the body mass index (BMI) was 23±2 kg/m2. The measured compartments were as following: intracellular water (IW), extracellular water (EW), protein component (PC), mineral component (MC), skeletal muscle mass (SMM) and body fat mass (BFM). Lean balance were examined for right and left arm (LA), trunk (T), right leg (RL) and left leg (LL). The comparison was made between the calculation derived by manual made measurements, using Matejka formula and parameters obtained by body composition analyzer (BCA) - Inbody 720 BCA Biospace. Used parameters for the comparison were muscle mass (SMM), body fat mass (BFM). Results: BCA obtained values were for: IW - 22.6±5L, EW - 13.5±2 L, PC - 9.8±0.9 kg, MC - 3.5±0.3, SMM - 27±3 kg, BFM - 13.8±4 kg. Lean balance showed following values for: RA - 2.45±0.2 kg, LA - 2.37±0.4, T - 20.9±5 kg, RL - 7.43±1 kg, and LL - 7.49 ±1.5 kg. SMM showed statistical difference between manual obtained value, 51±01% to BCA parameter 45.5±3% (p<0.001). Manual obtained values for BFM was lower (17±2%) than BCA obtained one, 19.5±5.9% (p<0.02). Discussion: The obtained results showed appropriate values for the examined age, regarding to all examined parameters which contribute to overview the body compartments, important for sport performing. Due to comparison between the manual and BCA assessment, we may conclude that manual measurements may differ from the certain ones, which is confirmed by statistical significance.

Keywords: athletes, body composition, bio electrical impedance, sports medicine

Procedia PDF Downloads 478

Authors: Sanaa Ragaee, Paragyani Bora, Wee Teng Tan, Xin Hu

Abstract:

Goji berry (Lycium barbarum) is a member of the family Solanaceae which is grown widely in China, Tibet, and other parts of Asia. Its fruits are 1–2 cm-long, bright orange-red ellipsoid berries and it has a long tradition as a food and medicinal plant. Goji berries are believed to boost immune system properties. The berries are considered an excellent source of macronutrients, micronutrients, vitamins, minerals and several bioactive components. Studies have shown effects of goji fruit on aging, neuroprotection, general well-being, fatigue/endurance, metabolism/energy expenditure, glucose control in diabetics and glaucoma, antioxidant properties, immunomodulation and anti-tumor activity. Goji berries are being used to prepare Goji beverage, and the remaining solid material is considered as by-product. The by-product is currently unused and disposed as waste despite its potential as a value-added food ingredient. Therefore, this study is intended to evaluate nutritional properties of Goji by-product and its potential applications in the baking industry. The Goji by-product was freeze dried and ground to pass through 1 mm screen prior to evaluation and food use. The Goji by-product was found to be a rich source of fiber (54%) and free phenolic components (1,307 µg/g), protein (13.6%), ash (3.3%) and fat (10%). Incorporation of the Goji by-product in muffins and cookies at various levels (10-40%) significantly improved the nutritional quality of the baked products. The baked products were generally accepted and highly rated by panelists at 20% replacement level. The results indicate the potential of Goji by-product as a value-added ingredient in particular as a source of dietary fiber and protein.

Keywords: Goji, by-product, phenolics, fibers, baked products

Procedia PDF Downloads 302

Authors: Jiang Xu, Daoping Wang, Qun Li, Yinghong Pan

Abstract:

2,4-Epibrassinolide (EBR), which is a kind of plant hormone Brassinosteroids (BRs), is widely studied and applied in the global scale but the proteomic characteristics of EBR alleviating low temperature stress in rice seedling leaves are still not clear. In this study, seeding rice of Nipponbare were treated with EBR and distilled water, then stressed at 4℃ or 26 ℃, and analyzed by mass spectrometry analysis, verified by parallel reaction monitoring technique (PRM). The results showed that 5778 proteins were identified in total and 4834 proteins were identified with quantitative information. Among them, 401 up-regulated and 220 down-regulated proteins may be related to EBR alleviating low temperature stress in rice seedling leaves. The molecular functions of most of up-regulated proteins are RNA binding and hydrolase activity and are mainly enriched in the pathways of carbon metabolism, folic acid synthesis, and amino acid biosynthesis. The down-regulated proteins are mainly related to catalytic activity and oxidoreductase activity and are mainly enriched in the pathways of limonene and pinene degradation, riboflavin metabolism, porphyrin and chlorophyll metabolism, and other metabolic pathways. PRM validation and literature analysis showed that NADP-malic acidase, peroxidase, 3-phosphoglycerate dehydrogenase, enolase, glyceraldehyde-3- phosphate dehydrogenase and pyruvate kinase are closely related to the effect of EBR on low temperature stress. These results also suggested that BRs could relieve the effect of low temperature stress on rice seed germination in many ways.

Keywords: 2, 4-Epibrassinolid, low temperature stress, proteomic analysis, rice

Procedia PDF Downloads 162

Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

Abstract:

Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

Procedia PDF Downloads 250

Authors: Danna Jia, Bin Li

Abstract:

Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

Procedia PDF Downloads 84