Search results for: serum proteins

Authors: Aouina Nabila Yasmina, Zine El Abidine Chaoui

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Recently, understanding the interactions of electrons with the DNA molecule and its components has attracted considerable interest because DNA is the main site damaged by ionizing radiation. The interactions of radiation with DNA induce a variety of molecular damage such as single-strand breaks, double-strand breaks, basic damage, cross-links between proteins and DNA, and others, or the formation of free radicals, which, by chemical reactions with DNA, can also lead to breakage of the strand. One factor that can contribute significantly to these processes is the effect of water hydration on the formation and reaction of radiation induced by these radicals in and / or around DNA. B-DNA requires about 30% by weight of water to maintain its native conformation in the crystalline state. The transformation depends on various factors such as sequence, ion composition, concentration and water activity. Partial dehydration converts it to DNA-A. The present study shows the results of theoretical calculations for positrons and electrons elastic scattering with DNA medium and water over a broad energy range from 10 eV to 100 keV. Indeed, electron elastic cross sections and elastic mean free paths are calculated using a corrected form of the independent atom method, taking into account the geometry of the biomolecule (SCAR macro). Moreover, the elastic scattering of electrons and positrons by atoms of the biomolecule was evaluated by means of relativistic (Dirac) partial wave analysis. Our calculated results are compared with theoretical data available in the literature in the absence of experimental data, in particular for positron. As a central result, our electron elastic cross sections are in good agreement with existing theoretical data in the range of 10 eV to 1 keV.

Keywords: elastic cross scrion, elastic mean free path, scar macro method, electron collision

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Authors: Nijole Savickiene, Antonella Di Sotto, Gabriela Mazzanti, Rasa Starselskyte, Silvia Di Giacomo, Annabella Vitalone

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Plant lectins are non-enzymic and non-immune origin proteins that specifically recognize and bind to various sugar structures and possess the activity to agglutinate cells and/or precipitate polysaccharides and glycoconjugates. The emerging evidences showed that plant lectins contribute not only to tumour cell recognition but also to cell adhesion and localization, to signal transduction, to mitogenic cytotoxicity and apoptosis. Among chitin-binding lectins, the Urtica dioica agglutinin (UDA), which is a complex of different isoforms, has been poorly studied for its biological activity. In this context and according to the increasing interest for lectins as novel antitumor drugs, present paper aimed at evaluating the potential antimutagenic activity of a lectin-like glycoprotein-enriched fraction from aerial part of Urtica dioica L. Aim: to evaluate the potential chemopreventive properties of a protein - lectin fraction from the aerial part of Urtica dioica. Materials and methods: Protein – lectin fraction has been tested for the antimutagenic activity in bacteria (50–800 mg/plate; Ames test by the preincubation method) and for the cytotoxicity on human hepatoma HepG2 cells (0.06–2 mg/mL; 24 and 48 h incubation). Results: Protein – lectin fraction from stinging nettle was not cytotoxic on HepG2 cells up to 2 mg/mL; conversely, it exhibited a strong antimutagenic activity against the mutagen 2-aminoanthracene (2AA) in all strains tested (maximum inhibition of 56.78 and 61% in TA98, TA100, and WP2uvrA strains, respectively, at 800 mg/plate). Discussion and conclusions: Protein – lectin fraction from Urtica dioica L. possesses antimutagenic and radical scavenging properties. Being 2AA a pro-carcinogenic agent, we hypothesize that the antimutagenicity of it can be due to the inhibition of CYP450-isoenzymes, involved in the mutagen bioactivation.

Keywords: lectins, antimutagenicity, chemoprevention, Urtica dioica

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Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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Authors: Sadaf Kalhori

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Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.

Keywords: cardiomyopathy, deferiprone, doxorubicin, rat

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Authors: Abiola A. Ojesanmi, Eric O. Amonsou

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The formation of soluble complexes is usually within a narrow pH range characterized by weak interactions. Moreover, the rigid conformation of globular proteins restricts the number of charged groups capable of interacting with polysaccharides, thereby limiting food applications. Hence, this study investigated the impact of tryptic-limited hydrolysis on the formation of Bambara protein-gum arabic soluble complexes formation. The electrostatic interactions were monitored through turbidimetry analysis. The Bambara protein hydrolysates at a specified degree of hydrolysis, and DHs (2, 5, and 7.5) were characterized using size exclusion chromatography, zeta potential, surface hydrophobicity, and intrinsic fluorescence. The stability of the complexes was investigated using differential scanning calorimetry and rheometry. The limited tryptic hydrolysis significantly widened the pH range of the formation of soluble complexes, with DH 5 having a wider range (pH 7.0 - 4.3) compared to DH 2 and DH 7.5, while there was no notable difference in the optimum complexation pH of the insoluble complexes. Larger peptides (140, 118 kDa) were detected in DH 2 relative to 144, 70, and 61 kDa in DH 5, which were larger than 140, 118, 48, and 32 kDa in DH 7. 5. An increase in net negative charge (- 30 Mv for DH 7.5) and a slight shift in the net neutrality (from pH 4.9 to 4.3) of the hydrolysates were observed which consequently impacted the electrostatic interaction with gum arabic. There was exposure of the hydrophobic amino acids up to 4-fold in comparison with the isolate and a red shift in maximum fluorescence wavelength in DH dependent manner following the hydrolysis. The denaturation temperature of the soluble complex from the hydrolysates shifted to higher values, having DH 5 with the maximum temperature (94.24 °C). A highly interconnected gel-like soluble complex network was formed having DH 5 with a better structure relative to DH 2 and 7.5. The study showed the use of limited tryptic hydrolysis at DH 5 as an effective approach to modify Bambara protein and provided a more stable and wider pH range of formation for soluble complex, thereby enhancing the food application.

Keywords: Bambara groundnut, gum arabic, interaction, soluble complex

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Authors: Numfon Rakkhumkaew, Takeru Kawasaki, Makoto Fujie, Takashi Yamada

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Chlorella viruses or chloroviruses contain a gene that encodes a function for chitin synthesis, which is expressed early in viral infection to produce chitin polysaccharide, a polymer of β-1, 4-linked GlcNAc, on the outside of Chlorella cell wall. Interestingly, chlorovirus system is an eco-friendly system which converses CO2 and solar energy from the environment into useful materials. However, infected Chlorella cells are lysed at the final stage of viral infection, and this phenomenon is caused the breaking down of polysaccharide. To postpone the lysing period and prolong the synthesis of chitin polysaccharide on cells, the slow growing virus incorporated with aphidicolin treatment, an inhibitor of DNA synthesis, was investigated. In this study, a total of 25 virus isolates from water samples in Japan region were analyzed for CHS (the gene for CH synthase) gene by PCR (polymerase chain reaction). The accumulation and appearance of chitin polysaccharide on infected cells were detected by biotinylated chitin-binding proteins WGA (wheat germ agglutinin)-biotin for chitin in conjunction with avidin-Cy 2 or Cy 3 and investigated by fluorescence microscopy, observed as green or yellow fluorescence over the cell surface. Among all chlorovirus isolates, cells infected with CNF1 revealed the accumulation of chitin over the cell surface within 30 min p.i. and continued to accumulate on cells until 4 h p.i. before cell lyses which was 1.6 times longer accumulation period than cells infected with CVK2 (prototype virus). Furthermore, addition of aphidicolin could extend the chitin accumulation on cells infected with CNF1 until 8 h p.i. before cell lyses. Whereas, CVK2-infected cells treated with aphidicolin could prolong the chitin synthesis only for 6 h p.i. before cell lyses. Therefore, chitin synthesis by Chlorella-virus system could be prolonged by using slow-growing viral isolates and with aphidicolin.

Keywords: chitin, chlorovirus, Chlorella virus, aphidicolin

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Authors: Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Linda Erlina, Tiwuk Susantiningsih

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Coronavirus disease-19 (COVID-19) is still one of the health problems. It can be a severe condition that is caused by a cytokine storm. In a cytokine storm, several proinflammatory cytokines are released massively. It destroys epithelial cells, and subsequently, it can cause death. The anti-inflammatory agent can be used to decrease the number of severe Covid-19 conditions. Melaleuca cajuputi is a plant that has antiviral, antibiotic, antioxidant, and anti-inflammatory activities. This study was carried out to analyze the prediction mechanism of the M. cajuputi extract from Lampung, Indonesia, as an anti-inflammatory agent for COVID-19. This study constructed a database of protein host target that was involved in the inflammation process of COVID-19 using data retrieval from GeneCards with the keyword “SARS-CoV2”, “inflammation,” “cytokine storm,” and “acute respiratory distress syndrome.” Subsequent protein-protein interaction was generated by using Cytoscape version 3.9.1. It can predict the significant target protein. Then the analysis of the Gene Ontology (GO) and KEGG pathways was conducted to generate the genes and components that play a role in COVID-19. The result of this study was 30 nodes representing significant proteins, namely NF-κβ, IL-6, IL-6R, IL-2RA, IL-2, IFN2, C3, TRAF6, IFNAR1, and DOX58. From the KEGG pathway, we obtained the result that NF-κβ has a role in the production of proinflammatory cytokines, which play a role in the COVID-19 cytokine storm. It is an important factor for macrophage transcription; therefore, it will induce inflammatory gene expression that encodes proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. In conclusion, the blocking of NF-κβ is the prediction mechanism of the M. cajuputi extract as an anti-inflammation agent for COVID-19.

Keywords: antiinflammation, COVID-19, cytokine storm, NF-κβ, M. cajuputi

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Authors: Eleni Poulou-Sidiropoulou, Charalampos N. Bompas, Martina Samiotaki, Alexios Vlamis-Gardikas

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The glutaredoxin (Grx) and thioredoxin (Trx) systems keep the intracellular environment reduced in almost all organisms. In Escherichia coli (E. coli), the Grx system relies on NADPH+ to reduce GSH reductase (GR), the latter reducing oxidized diglutathione to glutathione (GSH) which in turn reduces cytosolic Grxs, the electron donors for different intracellular substrates. In the Trx system, GR and GSH are replaced by Trx reductase (TrxR). Three of the Grxs of E. coli (Grx1, 2, 3) are reduced by GSH, while Grx4 is likely reduced by TrxR. Trx1 and Grx1 from E. coli may reduce ribonucleotide reductase Ia to ensure a constant supply of deoxyribonucleotides for the synthesis of DNA. The role of the other three Grxs is relatively unknown, especially for Grx2 that may amount up to 1 % of total cellular protein in the stationary phase of growth. The protein is known as a potent antioxidant, but no specific functions have been attributed to it. Herein, affinity chromatography of cellular extracts on immobilized Grx2, followed by MS analysis of the resulting eluates, was employed to identify protein ligands that could provide insights into the biological role of Grx2. Ionic, strong non-covalent, and covalent (disulfide) interactions with relevant proteins were detected. As a means of verification, the identified ligands were subjected to in silico docking with monothiol Grx2. In other experiments, protein extracts from E. coli cells lacking the gene for Grx2 (grxB) were compared to those of wild type. Taken together, the two approaches suggest that Grx2 is involved in protein synthesis, nucleotide metabolism, DNA damage repair, stress responses, and various metabolic processes. Grx2 appears as a versatile protein that may participate in a wide range of biological pathways beyond its known general antioxidant function.

Keywords: Escherichia coli, glutaredoxin 2, interactome, thiol-disulfide oxidoreductase

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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Postmenopausal osteoporosis is characterized by low bone density which leads to increased bone fragility and greater susceptibility to fracture. Current treatments for osteoporosis are dominated by drugs that inhibit bone resorption although they also suppress bone formation that may contribute to pathogenesis of osteonecrosis. To restore the extensive bone loss, there is a great need for anabolic treatments that induce osteoblasts to build new bone. Pre-osteoblastic cells produce proteins of the extra-cellular matrix, including type I collagen at first, and then to successively produce alkaline phosphatase (ALP) and osteocalcin during differentiation to osteoblasts. Finally, osteoblasts deposit calcium. Present study investigated the effects of egg yolk peptide (EYP) on osteogenic activities and bone matrix gene expressions in human osteoblastic MG-63 cells. The effects of EYP on cell proliferation, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization were measured. The expression of osteogenic genes including COL1A1 (collagen, type I, alpha 1), ALP, BGLAP (osteocalcin), and SPP1 (secreted phosphoprotein 1, osteopontin) were measured by quantitative realtime PCR. EYP dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. Furthermore, COL1A1, ALP, and SPP1 gene expressions were increased by EYP treatment. Present study suggested that EYP treatment enhanced osteogenic activities and increased bone matrix osteogenicgenes. These results could provide a mechanistic explanation for the bone-strengthening effects of EYP.

Keywords: egg yolk peptide, osteoblastic MG-63 cells, alkaline phosphatase, collagen synthesis, osteogenic genes, COL1A1, osteocalcin, osteopontin

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Authors: Magdalena Barbara Kaziuk, Waldemar Kosiba, Marek Jan Kuzniewski

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Introduction: Vitamin D3 has a proven pleiotropic effect, not only responsible for calcium and phosphate management, but also influencing normal functioning of the whole body. Aim: Evaluation of vitamin D3 resources and its effect on a nutritional status, obesity type and glomerular filtration in kidney transplant recipients. Methods: Group of 152 (81 women and 71 men, average age 47.8 ± 11.6 years) patients with a functioning renal transplant their body composition was assessed using the bioimpendance method (BIA) and anthropometric measurements more than 3 months after the transplant. The nutritional status and the obesity type were determined with the Waist to Height Ratio (WHtR) and the Waist to Hip Ratio (WHR). 25- Hydroxyvitamin D3 (25 (OH)D3) was determined, together with its correlation with the obesity type and the glomerular filtration rate (eGFR) calculated with the MDRD formula. Results: The mean 25 (OH)D3 level was 20.4 ng/ml. 30ng/ml was considered as a minimum correct level 22,7% of patients from the study group were classified to be a correct body weight, 56,7% of participants had an android type and 20,6% had a gynoid type. Significant correlation was observed between 25 (OH)D3 deficiency and abdominal obesity (p < 0.005) in patients. Furthermore, a statistically significant relationship was demonstrated between the 25 (OH)D3 levels and eGFR in patients after a kidney transplant. Patients with an android body type had lower eGFR versus those with the gynoid body type (p=0.004). Conclusions: Correct diet in patients after a kidney transplant determines minimum recommended serum levels of vitamin D3. Excessive fatty tissue, low levels of 25 (OH)D3), may be a predictor for android obesity and renal injury; therefore, correct diet and pharmacological management together with physical activities adapted to the physical fitness level of a patient are necessary.

Keywords: kidney transplantation, glomerular filtration rate, obesity, vitamin D3

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Authors: Vahab Behmanesh

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Metabolic syndrome is defined as having at least three of the five metabolic risk factors, including abdominal obesity, high blood pressure, high triglycerides, low HDL, and insulin resistance. Lifestyle changes towards reducing physical activity, unhealthy eating habits Especially the high-fat and high-carbohydrate diet is directly related to metabolic syndrome, and due to the epidemic of overweight and sedentary life, metabolic syndrome is a serious problem worldwide. On the other hand, vitamin D deficiency is considered as one of the most common problems in the world, which is related to the dysfunction of beta cells and insulin resistance, and therefore, vitamin D deficiency is considered as a factor in the occurrence of metabolic syndrome. 40 subjects (age: 16.12 ± 4.4 years and body mass index 25.61 ± 4.4 kg/m2) were randomly assigned to groups of aerobic exercise and placebo, aerobic exercise and vitamin D and placebo (no exercise) were divided. Vitamin D was taken at a dose of 50,000 units per week in a double-blind format for eight weeks, and the daily aerobic exercise program was performed for 50 to 60 minutes, three doses per week, with an intensity of 50-60% of the maximum heart rate. From one-way analysis of variance, Factorial variance analysis (2x2) repeated measurement and correlated t-test were used for data analysis. Aerobic exercise and vitamin D intake reduced all metabolic risk indicators and blood insulin (P < 0.05). However, the subjective feeling of hunger did not change significantly (P < 0.05). Regarding waist circumference and blood glucose, the effect of exercise combined with vitamin D consumption was greater than the corresponding effect in the vitamin D group (P < 0.05). Aerobic exercises and vitamin D intake are safe and effective for improving cardiometabolic health, Imam adds vitamin D to the exercise program has more benefits for weight and blood sugar control, which suggests prescribing it for patients with metabolic syndrome.

Keywords: vitamin D, aerobic exercise, metabolic control, adolescents

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Authors: Leila Karshenas, Hamidreza Khodaei, Behnaz Mahdavi

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Ovulation is a physiologic process with an inflammatory response that depends on a coordinated activity of gonadotropins and steroid hormones, as well as inflammatory mediators such as cytokines, prostaglandins, leptin, nitric oxide (NO), etc. Conjugated linoleic acid (CLA) is composed of polyunsaturated fatty acids (PUFA) found in dairy products, beef and lamb. There is strong evidence that dietary CLA affects mediators involved in ovulation. The aim of this study was to determine the effects of different doses of dietary CLA on systemic and local hormones and factors involved in ovulation. In this case-control study, 80 (50±2-day old) female mice were randomly divided into four groups (C as the controls and T1, T2 and T3 as the treatment groups). There were four replicates in each group and there were five mice in every replicate (20 mice, in total). The mice in the control group were fed with no CLA in their diet but the ones in the treatment group received 0.1, 0.3 and 0.5g/kg of CLA (replacing corn oil in the diet), respectively for 120 days. Later on, blood samples were obtained from the tails of animals that displayed estrus signs and estradiol (E2), progesterone (P4), LH, FSH, NO, leptin and TNFα were measured. Furthermore, the effects of CLA on the ovarian production of prostaglandins (PGs) and NO were investigated. The data were analyzed by SAS software.CLA significantly decreased serum levels of FSH (p<0.05), LH, estradiol, NO, leptin and TNFα (p<0.01). In addition, CLA decreased progesterone levels but this effect was statistically insignificant. The significantly negative effects of CLA were seen on the ovarian production of PGE2 and PGF2α (p<0.01).It seems that CLA may play an effective role in reducing the ovulation rate in mice as CLA adversely affected female reproduction and it had negative effects on systemic and local hormones involved in ovulation.

Keywords: conjugated linoleic acid, nitric oxide, ovary, ovulation, prostaglandin, gonadotropin

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Authors: Hyun-jin Kim, Gumgyung Gu, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min

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Background: Ovarian carcinoma is the fourth most common cause of cancer-related death in women worldwide. HE4, a novel marker for ovarian cancer could be used for monitoring recurrence or progression of disease in patients with invasive epithelial ovarian carcinoma. It is further intended to be used in conjunction with CA 125 to estimate the risk of epithelial ovarian cancer in women presenting with an adnexal mass. In this study, we aim to evaluate the analytical performance and clinical utility of HE4 assay using Architect i 2000SR(Abbott Diagnostics, USA). Methods: The precision was evaluated according to Clinical and Laboratory Standards Institute(CLSI) EP5 guideline. Three levels of control materials were analyzed twice a day in duplicate manner over 20 days. We calculated within run and total coefficient of variation (CV) at each level of control materials. The linearity was evaluated based on CLSI EP6 guideline. Five levels of calibrator were prepared by mixing high and low level of calibrators. For 43 women with adnexal masses, HE4 and CA 125 were measured and Risk of ovarian malignancy (ROMA) scores were calculated. The patients’ medical records were reviewed to determine the clinical utility of HE4 and ROMA score. Results: In a precision study, the within-run and total CV were 2.0 % and 2.3% for low level of control material, 1.9% and 2.4% for medium level and 0.5 % and 1.1% for high level, respectively. The linear range of HE4 was 14.63 to 1475.15pmol/L. Of the 43 patients, two patients in pre-menopausal group showed the ROMA score above the cut-off level (7.3%). One of them showed CA 125 level within the reference range, while the HE4 was higher than the cut-off. Conclusion: The overall analytical performance of HE4 assay using Architect showed high precision and good linearity within clinically important range. HE4 could be an useful marker for managing patients with adnexal masses.

Keywords: HE4, CA125, ROMA, evaluation, performance

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Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

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Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

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Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

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Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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Authors: Masoud Soltanialvar, Ali Bagherpour

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Documented cases of human infection with H9N2 avian influenza viruses, first detected in 1999 in Hong Kong and China, indicate that these viruses can be directly transmitted from birds to humans. In this study, we characterized the mutation in the Hemagglutinin (HA) genes and proteins that correlates with a shift in affinity of the Hemagglutinin (HA) protein from the “avian” type sialic receptors to the “human” type in 10 Iranian isolates. We delineated the genomes and receptor binding profile of HA gene of some field isolates and established their phylogenetic relationship to the other Asian H9N2 sub lineages. A total of 1200 tissue samples collected from 40 farms located in various states of Iran during 2008 – 2010 as part of a program to monitor Avian Influenza Viruses (AIV) infection. To determine the genetic relationship of Iranian viruses, the Hemagglutinin (HA) genes from ten isolates were amplified and sequenced (by RT-PCR method). Nucleotide sequences (orf) of the (HA) genes were used for phylogenetic tree construction. Deduced amino acid sequences showed the presence of L226 (234 in H9 numbering) in all ten Iranian isolates which indicates a preference to binding of α (2–6) sialic acid receptors, so these Iranian H9N2 viruses have the potential to infect human beings. These isolates showed high degree of homology with 2 human H9N2 isolates A/HK/1073/99, A/HK/1074/99. Phylogenetic analysis of showed that all the HA genes of the Iranian H9N2 viruses fall into a single group within a G1-like sublineage which had contributed as donor of six internal genes to H5N1 highly pathogenic avian influenza. The results of this study indicated that all Iranian viruses have the potential to emerge as highly pathogenic influenza virus, and considering the homology of these isolates with human H9N2 strains, it seems that the potential of these avian influenza isolates to infect human should not be overlooked.

Keywords: influenza virus, hemagglutinin, neuraminidase, Iran

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Authors: Andrey V. Khromov, Antonida V. Makhotenko, Ekaterina A. Snigir, Svetlana S. Makarova, Natalia O. Kalinina, Valentin V. Makarov, Mikhail E. Taliansky

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Due to its simplicity, CRISPR/Cas9 has become widely used and capable of inducing mutations in the genes of organisms of various kingdoms. The aim of this work was to develop applications for the efficient modification of DNA coding sequences of phytoene desaturase (PDS), coilin and vacuolar invertase (Solanum tuberosum) genes, and to develop a new nanoparticles carrier efficient technology to deliver the CRISPR/Cas9 system for editing the plant genome. For each of the genes - coilin, PDS and vacuolar invertase, five single RNA guide (sgRNAs) were synthesized. To determine the most suitable nanoplatform, two types of NP platforms were used: magnetic NPs (MNPS) and gold NPs (AuNPs). To test the penetration efficiency, they were functionalized with fluorescent agents - BSA * FITS and GFP, as well as labeled Cy3 small-sized RNA. To measure the efficiency, a fluorescence and confocal microscopy were used. It was shown that the best of these options were AuNP - both in the case of proteins and in the case of RNA. The next step was to check the possibility of delivering components of the CRISPR/Cas9 system to plant cells for editing target genes. AuNPs were functionalized with a ribonucleoprotein complex consisting of Cas9 and corresponding to target genes sgRNAs, and they were biolistically bombarded to axillary buds and apical meristems of potato plants. After the treatment by the best NP carrier, potato meristems were grown to adult plants. DNA isolated from this plants was sent to a preliminary fragment of the analysis to screen out the non-transformed samples, and then to the NGS. The present work was carried out with the financial support from the Russian Science Foundation (grant No. 16-16-04019).

Keywords: biobombardment, coilin, CRISPR/Cas9, nanoparticles, NPs, PDS, sgRNA, vacuolar invertase

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Authors: Ife O. Bolaji

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Environmental concerns arising from the use of fossil fuels has increased the interest in the development of renewable and sustainable sources of energy. This would minimize the dependence on fossil fuels and serve as future alternatives. Organic wastes contain carbohydrates, proteins and lipids, which can be utilised as carbon sources for the production of bio-based products. Cellulose is the most abundant natural biopolymer, being the main structural component of lignocellulosic materials. The aim of this project is to develop a biological process for the hydrolysis and fermentation of organic wastes into ethanol and organic acids. The hydrolysis and fermentation processes are integrated in a single vessel using undefined mixed culture microorganisms. The anaerobic fermentation of microcrystalline cellulose was investigated in continuous and batch reactors at 25°C with an appropriate growth medium for cellulase formation, hydrolysis, and fermentation. The reactors were inoculated with soil (B1, C1, C3) or sludge from an anaerobic digester (B2, C2) and the breakdown of cellulose was monitored by measuring the production of ethanol, organic acids and the residual cellulose. The batch reactors B1 and B2 showed negligible microbial activity due to inhibition while the continuous reactors, C1, C2 and C3, exhibited little cellulose hydrolysis which was concealed by the cellulose accumulation in the reactor. At the end of the continuous operation, the reactors C1, C2 and C3 were operated under batch conditions. 48%, 34% and 42% cellulose had been fermented by day 88, 55 and 55 respectively of the batch fermentation. Acetic acid, ethanol, propionic acid and butyric acids were the main fermentation products in the reactors. A stable concentration of 0.6 g/l ethanol and 5 g/L acetic acid was maintained in C3 for several weeks due to reduced activity of methanogens caused by the decrease in pH. Thus far, the results have demonstrated that mixed microbial culture is capable of hydrolysing and fermenting cellulose under lenient conditions. The fermentation of cellulose has been found effective in a combination of continuous and batch processes.

Keywords: cellulose, hydrolysis, mixed culture, organic waste

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Authors: Hongquan Zhang

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Inspired by endogenous protein motors, researchers have constructed various synthetic DNA motors based on the specificity and predictability of Watson-Crick base pairing. However, the application of DNA motors to signal amplification and biosensing is limited because of low mobility and difficulty in real-time monitoring of the walking process. The objective of our work was to construct a new type of DNA motor termed target-triggered DNA motors that can walk for hundreds of steps in response to a single target binding event. To improve the mobility and processivity of DNA motors, we used gold nanoparticles (AuNPs) as scaffolds to build high-density, three-dimensional tracks. Hundreds of track strands are conjugated to a single AuNP. To enable DNA motors to respond to specific protein and nucleic acid targets, we adapted the binding-induced DNA assembly into the design of the target-triggered DNA motors. In response to the binding of specific target molecules, DNA motors are activated to autonomously walk along AuNP, which is powered by a nicking endonuclease or DNAzyme-catalyzed cleavage of track strands. Each moving step restores the fluorescence of a dye molecule, enabling monitoring of the operation of DNA motors in real time. The motors can translate a single binding event into the generation of hundreds of oligonucleotides from a single nanoparticle. The motors have been applied to amplify the detection of proteins and nucleic acids in test tubes and live cells. The motors were able to detect low pM concentrations of specific protein and nucleic acid targets in homogeneous solutions without the need for separation. Target-triggered DNA motors are significant for broadening applications of DNA motors to molecular sensing, cell imagining, molecular interaction monitoring, and controlled delivery and release of therapeutics.

Keywords: biosensing, DNA motors, gold nanoparticles, signal amplification

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Authors: F. Bellali, M. Kharroubi, Y. Rady, N. Bourhim

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In Morocco, fish processing industry is an important source income for a large amount of by-products including skins, bones, heads, guts, and scales. Those underutilized resources particularly scales contain a large amount of proteins and calcium. Sardina plichardus scales from resulting from the transformation operation have the potential to be used as raw material for the collagen production. Taking into account this strong expectation of the regional fish industry, scales sardine upgrading is well justified. In addition, political and societal demands for sustainability and environment-friendly industrial production systems, coupled with the depletion of fish resources, drive this trend forward. Therefore, fish scale used as a potential source to isolate collagen has a wide large of applications in food, cosmetic, and biomedical industry. The main aim of this study is to isolate and characterize the acid solubilize collagen from sardine fish scale, Sardina pilchardus. Experimental design methodology was adopted in collagen processing for extracting optimization. The first stage of this work is to investigate the optimization conditions of the sardine scale deproteinization on using response surface methodology (RSM). The second part focus on the demineralization with HCl solution or EDTA. And the last one is to establish the optimum condition for the isolation of collagen from fish scale by solvent extraction. The advancement from lab scale to pilot scale is a critical stage in the technological development. In this study, the optimal condition for the deproteinization which was validated at laboratory scale was employed in the pilot scale procedure. The deproteinization of fish scale was then demonstrated on a pilot scale (2Kg scales, 20l NaOH), resulting in protein content (0,2mg/ml) and hydroxyproline content (2,11mg/l). These results indicated that the pilot-scale showed similar performances to those of lab-scale one.

Keywords: deproteinization, pilot scale, scale, sardine pilchardus

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Authors: Yeon Ho Je

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A novel recombinant baculovirus, NeuroBactrus, was constructed to develop an improved baculovirus insecticide with additional beneficial properties, such as a higher insecticidal activity and improved recovery, compared to wild-type baculovirus. For the construction of NeuroBactrus, the Bacillus thuringiensis crystal protein gene (here termed cry1-5) was introduced into the Autographa californica nucleopolyhedrovirus (AcMNPV) genome by fusion of the polyhedrin–cry1-5–polyhedrin genes under the control of the polyhedrin promoter. In the opposite direction, an insect-specific neurotoxin gene, AaIT, from Androctonus australis was introduced under the control of an early promoter from Cotesia plutellae bracovirus by fusion of a partial fragment of orf603. The polyhedrin–Cry1-5–polyhedrin fusion protein expressed by the NeuroBactrus was not only occluded into the polyhedra, but it was also activated by treatment with trypsin, resulting in an_65-kDa active toxin. In addition, quantitative PCR revealed that the neurotoxin was expressed from the early phase of infection. NeuroBactrus showed a high level of insecticidal activity against Plutella xylostella larvae and a significant reduction in the median lethal time against Spodoptera exigua larvae compared to those of wild-type AcMNPV. Rerecombinant mutants derived from NeuroBactrus in which AaIT and/or cry1-5 were deleted were generated by serial passages in vitro. Expression of the foreign proteins (B. thuringiensis toxin and AaIT) was continuously reduced during the serial passage of the NeuroBactrus. Moreover, polyhedra collected from S. exigua larvae infected with the serially passaged NeuroBactrus showed insecticidal activity similar to that of wild-type AcMNPV. These results suggested that NeuroBactrus could be recovered to wild-type AcMNPV through serial passaging.

Keywords: baculovirus, insecticide, neurotoxin, neurobactrus

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Authors: Ali Kassem, Aly Taha, Abeer Hassan, Kazuhide Higuchi

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Introduction: Trans arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is usually followed by hepatic dysfunction that limits its efficacy. L-carnitine is recently studied as hepatoprotective agent. Our aim is to evaluate the L-carnitine effects against the deterioration of liver functions after TACE. Method: 53 patients with intermediate stage HCC were assigned into two groups; L-carnitine group (26 patients) who received L-carnitine 300 mg tablet twice daily from 2 weeks before to 12 weeks after TACE and control group (27 patients) without L-carnitine therapy. 28 of studied patients received branched chain amino acids granules. Results: There were significant differences between L-carnitine Vs. control group in mean serum albumin change from baseline to 1 week and 4 weeks after TACE (p < 0.05). L-Carnitine maintained Child-Pugh score at 1 week after TACE and exhibited improvement at 4 weeks after TACE (p < 0.01 Vs 1 week after TACE). Control group has significant Child-Pugh score deterioration from baseline to 1 week after TACE (p < 0.05) and 12 weeks after TACE (p < 0.05). There were significant differences between L-carnitine and control groups in mean Child-Pugh score change from baseline to 4 weeks (p < 0.05) and 12 weeks after TACE (p < 0.05). L-carnitine displayed improvement in (PT) from baseline to 1 week, 4 w (p < 0.05) and 12 weeks after TACE. PT in control group declined less than baseline along all follow up intervals. Total bilirubin in L-carnitine group decreased at 1 week post TACE while in control group, it significantly increased at 1 week (p = 0.01). ALT and C-reactive protein elevation were suppressed at 1 week after TACE in Lcarnitine group. The hepatoprotective effects of L-carnitine were enhanced by concomitant use of branched chain amino acids. Conclusion: L-carnitine and BCAA combination therapy offer a novel supportive strategy after TACE in HCC patients.

Keywords: hepatocellular carcinoma, L-carnitine, liver functions , trans-arterial embolization

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Authors: Basanti Ekka, Talis Juhna

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Dairy industrial effluents originated by the typical processing activities are composed of various organic and inorganic constituents, and these include proteins, fats, inorganic salts, antibiotics, detergents, sanitizers, pathogenic viruses, bacteria, etc. These contaminants are harmful to not only human beings but also aquatic flora and fauna. Because consisting of large classes of contaminants, the specific targeted removal methods available in the literature are not viable solutions on the industrial scale. Therefore, in this on-going research, a series of coagulation, electrochemical, and catalytic methods will be employed. The bulk coagulation and electrochemical methods can wash off most of the contaminants, but some of the harmful chemicals may slip in; therefore, specific catalysts designed and synthesized will be employed for the removal of targeted chemicals. In the context of Latvian dairy industries, presently, work is under progress on the characterization of dairy effluents by total organic carbon (TOC), Inductively Coupled Plasma Mass Spectrometry (ICP-MS)/ Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), High-Performance Liquid Chromatography (HPLC), Gas Chromatography-Mass Spectrometry (GC-MS), and Mass Spectrometry. After careful evaluation of the dairy effluents, a cost-effective natural coagulant will be employed prior to advanced electrochemical technology such as electrocoagulation and electro-oxidation as a secondary treatment process. Finally, graphene oxide (GO) based hybrid materials will be used for post-treatment of dairy wastewater as graphene oxide has been widely applied in various fields such as environmental remediation and energy production due to the presence of various oxygen-containing groups. Modified GO will be used as a catalyst for the removal of remaining contaminants after the electrochemical process.

Keywords: catalysis, dairy wastewater, electrochemical method, graphene oxide

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Authors: Kadry M. Sadek, Tarek K. Abouzed, Mousa A. Ayoub

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The presence of endocrine-disrupting compounds, such as bisphenol A (BPA), in the environment can cause serious health problems. However, there are controversial opinions. This study investigated the reproductive, metabolic, oxidative and immunologic-disrupting effects of bisphenol A in male rabbits. Rabbits were divided into five groups. The first four rabbit groups were administered oral BPA (1, 10, 50, or 100 mg/kg/day) for ten weeks. The fifth group was administered corn oil as the vehicle. BPA significantly decreased serum testosterone, estradiol and the free androgen index (FAI) and significantly increased sex hormone binding globulin (SHBG) compared with the placebo group. The higher doses of BPA showed a significant decrease in follicular stimulating hormone (FSH) and luteinizing hormone (LH). A significant increase in blood glucose levels was identified in the BPA groups. The non-significant difference in insulin levels is a novel finding. The cumulative testicular toxicity of BPA was clearly demonstrated by the dose-dependent decrease in absolute testes weight, primary measures of semen quality and a significant increase in testicular malonaldehyde (MDA). Moreover, BPA significantly decreased total antioxidant capacity (TAC) and significantly increased immunoglobulin G (IgG) at the highest concentration. Our results suggest that BPA, especially at higher doses, is associated with many adverse effects on metabolism, oxidative stress, immunity, sperm quality and markers of androgenic action. These results may reflect the estrogenic effects of BPA, which we hypothesize could be related, in part, to an inhibitory effect on testicular steroidogenesis. The induction of oxidative stress by BPA may play an additional role in testicular toxicity. These results suggest that BPA poses a threat to endocrine and reproductive functions.

Keywords: bisphenol A, oxidative stress, rabbits, semen quality, steroidogenesis

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Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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Authors: Magdalena B. Kaziuk, Waldemar Kosiba

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Background: In the XXI century we have to deal with the epidemic of obesity which is important risk factor for the cardiovascular and kidney diseases. Lipo proteins are directly involved in the atherosclerotic process. Non-high-density lipo protein (non-HDL) began following widespread recognition of its superiority over LDL as a measurement of vascular event risk. Non-HDL includes residual risk which persists in patients after achieved recommended level of LDL. Materials and Methods: The study covered 111 patients (52 females, 59 males, age 51,91±14 years), hospitalized on the intern department. Body composition was assessed using the bioimpendance method and anthropometric measurements. Physical activity data were collected during the interview. The nutritional status and the obesity type were determined with the Waist to Height Ratio and the Waist to Hip Ratio. A function of the kidney was evaluated by calculating the estimated glomerular filtration rate (eGFR) using MDRD formula. Non-HDL was calculated as a difference between concentration of the Total and HDL cholesterol. Results: 10% of patients were found to be underweight; 23.9 % had correct body weight; 15,08 % had overweight, while the remaining group had obesity: 51,02 %. People with the android shape have higher non-HDL cholesterol versus with the gynoid shape (p=0.003). The higher was non-HDL, the lower eGFR had studied subjects (p < 0.001). Significant correlation was found between high non-HDL and incorrect dietary habits in patients avoiding eating vegetables, fruits and having low physical activity (p < 0.005). Conclusions: Android type of figure raises the residual risk of the heart disease associated with higher levels of non-HDL. Increasing physical activity in these patients reduces the level of non-HDL. Non-HDL seems to be the best predictor among all cholesterol measures for the cardiovascular events and worsening eGFR.

Keywords: obesity, non-HDL cholesterol, glomerular filtration rate, lifestyle

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Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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Authors: Murat Emre, Zeynep Tufekcioglu

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Objective: We describe a patient with late onset phenylketonuria which presented with rapidly progressive dementia and parkinsonism that were reversible after management. Background: Phenylketonuria is an autosomal recessive disorder due to mutations in the phenylalanine hydroxlase gene. It normally presents in childhood, in rare cases, however, it may have its onset in adulthood and may mimic other neurological disorders. Case description: A previously normal functioning, 59 year old man was admitted for blurred vision, cognitive impairment and gait difficulty which emerged over the past eight months. In neurological examination he had brisk reflexes, slow gait and left-dominant parkinsonism. Mini-mental state examination score was 25/30, neuropsychological testing revealed a dysexecutive syndrome with constructional apraxia and simultanagnosia. In cranial MRI there were bilateral diffuse hyper-intense lesions in parietal and occipital white matter with no significant atrophy. Electroencephalography showed diffuse slowing with predominance of teta waves. In cerebrospinal fluid examination protein level was slightly elevated (61mg/dL), oligoclonal bands were negative. Electromyography was normal. Routine laboratory examinations for rapidly progressive dementia and parkinsonism were also normal. Serum amino acid levels were determined to explore metabolic leukodystrophies and phenylalanine level was found to be highly elevated (1075 µmol/L) with normal tyrosine (61,20 µmol/L). His cognitive impairment and parkinsonian symptoms improved following three months of phenylalanine restricted diet. Conclusions: Late onset phenylketonuria is a rare, potentially reversible cause of rapidly progressive parkinsonism with dementia. It should be considered in the differential diagnosis of patients with suspicious features.

Keywords: dementia, neurology, Phenylketonuria, rapidly progressive parkinsonism

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Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

Procedia PDF Downloads 142