Search results for: tyrosine kinase inhibitors

Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

Abstract:

Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

Procedia PDF Downloads 69

Authors: Philip Friedlander, John Rutledge, Jason Suh

Abstract:

Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

Procedia PDF Downloads 76

Authors: Regiane A. Oliveira, Carlos E. Vaz Rossell, Rubens Maciel Filho

Abstract:

Lactic acid, besides a valuable chemical may be considered a platform for other chemicals. In fact, the feasibility of hemicellulosic sugars as feedstock for lactic acid production process, may represent the drop of some of the barriers for the second generation bioproducts, especially bearing in mind the 5-carbon sugars from the pre-treatment of sugarcane bagasse. Bearing this in mind, the purpose of this study was to use the hemicellulosic liquor from sugarcane bagasse as a substrate to produce lactic acid by fermentation. To release of sugars from hemicellulose it was made a pre-treatment with a diluted sulfuric acid in order to obtain a xylose's rich liquor with low concentration of inhibiting compounds for fermentation (≈ 67% of xylose, ≈ 21% of glucose, ≈ 10% of cellobiose and arabinose, and around 1% of inhibiting compounds as furfural, hydroxymethilfurfural and acetic acid). The hemicellulosic sugars associated with 20 g/L of yeast extract were used in a fermentation process with Lactobacillus plantarum to produce lactic acid. The fermentation process pH was controlled with automatic injection of Ca(OH)2 to keep pH at 6.00. The lactic acid concentration remained stable from the time when the glucose was depleted (48 hours of fermentation), with no further production. While lactic acid is produced occurs the concomitant consumption of xylose and glucose. The yield of fermentation was 0.933 g lactic acid /g sugars. Besides, it was not detected the presence of by-products, what allows considering that the microorganism uses a homolactic fermentation to produce its own energy using pentose-phosphate pathway. Through facultative heterofermentative metabolism the bacteria consume pentose, as is the case of L. plantarum, but the energy efficiency for the cell is lower than during the hexose consumption. This implies both in a slower cell growth, as in a reduction in lactic acid productivity compared with the use of hexose. Also, L. plantarum had shown to have a capacity for lactic acid production from hemicellulosic hydrolysate without detoxification, which is very attractive in terms of robustness for an industrial process. Xylose from hydrolyzed bagasse and without detoxification is consumed, although the hydrolyzed bagasse inhibitors (especially aromatic inhibitors) affect productivity and yield of lactic acid. The use of sugars and the lack of need for detoxification of the C5 liquor from sugarcane bagasse hydrolyzed is a crucial factor for the economic viability of second generation processes. Taking this information into account, the production of second generation lactic acid using sugars from hemicellulose appears to be a good alternative to the complete utilization of sugarcane plant, directing molasses and cellulosic carbohydrates to produce 2G-ethanol, and hemicellulosic carbohydrates to produce 2G-lactic acid.

Keywords: fermentation, lactic acid, hemicellulosic sugars, sugarcane

Procedia PDF Downloads 373

Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

Abstract:

Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

Procedia PDF Downloads 83

Authors: Ila Shukla, Lubna Azmi, Shyam Sunder Gupta, C. V. Rao

Abstract:

Treatments against Hepatitis-C virus (HCV) are already available, but the current high cost of such treatments limit them to wealthy patients only. Hence our current study is aimed at the rectification of HCV infection by using Lichen rangiferinus (LRE) extract in in vitro cultures. Anti-HCV activity of the given extract was evaluated using the virus grown in cell culture (HCVcc). Two control inhibitors, erlotinib and telaprevir, were systematically included in each experiment. At the end of the incubation period, we evaluated cell viability and viral replication. The LRE inhibited the growth of HCV in a dose dependent manner.

Keywords: Erlotinib, Hepatitis C, Lichen rangiferinus, Telaprevir

Procedia PDF Downloads 336

Authors: Ajay Pratap Singh Lodhi, Deepak Kumar

Abstract:

Vegetable oil-based environmentally friendly metalworking fluids (MWFs) are formulated. The tribological performance, cytotoxicity, and corrosion resistance of the formulated fluids (FFs) are evaluated and benchmarked with commercial mineral oil-based MWFs (CF). Results show that FFs exhibited better machining characteristics (roughness, cutting forces, and surface morphology) during machining than CF. MTT assay and Live dead cell assay confirm the cytocompatibility nature of the FFs relative to the toxic CF. Electrochemical analysis shows that FFs and CF exhibited comparable corrosion current density.

Keywords: corrosion inhibitors, cytotoxicity, machining, MTT assay, Taguchi method, vegetable oil

Procedia PDF Downloads 188

Authors: Agnieszka Krzemińska, Katarzyna Świderek, Vicente Molinier, Piotr Paneth

Abstract:

In order to understand in details the interactions between ligands and the enzyme isotope effects were studied between clinically used drugs that bind in the active site of Human Immunodeficiency Virus Reverse Transcriptase, HIV-1 RT, as well as triazole-based inhibitor that binds in the allosteric pocket of this enzyme. The magnitudes and origins of the resulting binding isotope effects were analyzed. Subsequently, binding isotope effect of the same triazole-based inhibitor bound in the active site were analyzed and compared. Together, these results show differences in binding origins in two sites of the enzyme and allow to analyze binding mode and place of newly synthesized inhibitors. Typical protocol is described below on the example of triazole ligand in the allosteric pocket. Triazole was docked into allosteric cavity of HIV-1 RT with Glide using extra-precision mode as implemented in Schroedinger software. The structure of HIV-1 RT was obtained from Protein Data Bank as structure of PDB ID 2RKI. The pKa for titratable amino acids was calculated using PROPKA software, and in order to neutralize the system 15 Cl- were added using tLEaP package implemented in AMBERTools ver.1.5. Also N-terminals and C-terminals were build using tLEaP. The system was placed in 144x160x144Å3 orthorhombic box of water molecules using NAMD program. Missing parameters for triazole were obtained at the AM1 level using Antechamber software implemented in AMBERTools. The energy minimizations were carried out by means of a conjugate gradient algorithm using NAMD. Then system was heated from 0 to 300 K with temperature increment 0.001 K. Subsequently 2 ns Langevin−Verlet (NVT) MM MD simulation with AMBER force field implemented in NAMD was carried out. Periodic Boundary Conditions and cut-offs for the nonbonding interactions, range radius from 14.5 to 16 Å, are used. After 2 ns relaxation 200 ps of QM/MM MD at 300 K were simulated. The triazole was treated quantum mechanically at the AM1 level, protein was described using AMBER and water molecules were described using TIP3P, as implemented in fDynamo library. Molecules 20 Å apart from the triazole were kept frozen, with cut-offs established on range radius from 14.5 to 16 Å. In order to describe interactions between triazole and RT free energy of binding using Free Energy Perturbation method was done. The change in frequencies from ligand in solution to ligand bounded in enzyme was used to calculate binding isotope effects.

Keywords: binding isotope effects, molecular dynamics, HIV, reverse transcriptase

Procedia PDF Downloads 431

Authors: Jineetkumar Gawad, Chandrakant Bonde

Abstract:

Tuberculosis (TB) is a major worldwide concern whose control has been exacerbated by HIV, the rise of multidrug-resistance (MDR-TB) and extensively drug resistance (XDR-TB) strains of Mycobacterium tuberculosis. The interest for newer and faster acting antitubercular drugs are more remarkable than any time. To search potent compounds is need and challenge for researchers. Here, we tried to design lead for inhibition of Decaprenyl phosphoryl-β-D-ribose 2′-epimerase (DprE1) enzyme. Arabinose is an essential constituent of mycobacterial cell wall. DprE1 is a flavoenzyme that converts decaprenylphosphoryl-D-ribose into decaprenylphosphoryl-2-keto-ribose, which is intermediate in biosynthetic pathway of arabinose. Latter, DprE2 converts keto-ribose into decaprenylphosphoryl-D-arabinose. We had a selection of 23 compounds from azaindole series for computational study, and they were drawn using marvisketch. Ligands were prepared using Maestro molecular modeling interface, Schrodinger, v10.5. Common pharmacophore hypotheses were developed by applying dataset thresholds to yield active and inactive set of compounds. There were 326 hypotheses were developed. On the basis of survival score, ADRRR (Survival Score: 5.453) was selected. Selected pharmacophore hypotheses were subjected to virtual screening results into 1000 hits. Hits were prepared and docked with protein 4KW5 (oxydoreductase inhibitor) was downloaded in .pdb format from RCSB Protein Data Bank. Protein was prepared using protein preparation wizard. Protein was preprocessed, the workspace was analyzed using force field OPLS 2005. Glide grid was generated by picking single atom in molecule. Prepared ligands were docked with prepared protein 4KW5 using Glide docking. After docking, on the basis of glide score top-five compounds were selected, (5223, 5812, 0661, 0662, and 2945) and the glide docking score (-8.928, -8.534, -8.412, -8.411, -8.351) respectively. There were interactions of ligand and protein, specifically HIS 132, LYS 418, TRY 230, ASN 385. Pi-pi stacking was observed in few compounds with basic Imidazo [4,5-b] pyridine ring. We had basic azaindole ring in parent compounds, but after glide docking, we received compounds with Imidazo [4,5-b] pyridine as a basic ring. That might be the new lead in the process of drug discovery.

Keywords: DprE1 inhibitors, in silico drug designing, imidazo [4, 5-b] pyridine, lead, tuberculosis

Procedia PDF Downloads 154

Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

Abstract:

The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

Procedia PDF Downloads 334

Authors: El-Sohaimy Sobhy A., Androsova Natalia, Toshev Abuvali Djabarovec

Abstract:

The conditions of the isolation of proteins from the hemp seeds were optimized in the current work. Moreover, the physicochemical and functional properties of hemp protein isolate were evaluated for its potential application in food manufacturing. The elastin protein is the most predominant protein in the protein profile with a molecular weight of 58.1 KDa, besides albumin, with a molecular weight of 31.5 KDa. The FTIR spectrum detected the absorption peaks of the amide I in 1750 and 1600 cm⁻¹, which pointed to C=O stretching while N-H was stretching at 1650-1580 cm⁻¹. The peak at 3250 was related to N-H stretching of primary aliphatic amine (3400-3300 cm⁻¹), and the N-H stretching for secondary (II) amine appeared at 3350-3310 cm⁻¹. Hemp protein isolate (HPI) was showed high content of arginine (15.52 g/100 g), phenylalanine+tyrosine (9.63 g/100 g), methionine + cysteine (5.49 g/100 g), leucine + isoleucine (5.21 g/100 g) and valine (4.53 g/100 g). It contains a moderate level of threonine (3.29 g/100 g) and lysine (2.50 g/100 g), with the limiting amino acid being a tryptophan (0.22 g/100 g HPI). HPI showed high water-holding capacity (4.5 ± 2.95 ml/g protein) and oil holding capacity (2.33 ± 1.88 ml/g) values. The foaming capacity of HPI was increased with increasing the pH values to reach the maximum value at pH 11 (67.23±3.20 %). The highest emulsion ability index of HPI was noted at pH 9 (91.3±2.57 m2/g) with low stability (19.15±2.03).

Keywords: Cannabis sativa ssp., protein isolate, isolation conditions, amino acid composition, chemical properties, functional properties

Procedia PDF Downloads 180

Authors: Kalyan S. Ghosh, B. L. Dhananjaya

Abstract:

Snake bite causes fatal injuries in multi-organs and even many deaths due to several adverse physiological effects of various phospholipases (PLA2s) present in snake venom. Though these PLA2s bear highly homologues sequences and also structure but exhibit a different extent of those pharmacological effects. In this study, we have explored the difference in the neurotoxicity of two PLA2 namely PLA2-V, PLA2-VIIIa present in the venom from Vipera russellii. Bioinformatics studies on sequences of these two proteins along with detailed structural comparison enable us to explore the differences unambiguously. The identification of the residues involved in neurotoxicity will further lead towards proper designing of inhibitors against such killing effects of the venom.

Keywords: electrostatic potential, homology modeling, hydrophobicity, neurotoxicity, Phospholipase A2

Procedia PDF Downloads 437

Authors: Jiaojiao Zhang

Abstract:

Boar sperm quality, as an important indicator of reproductive efficiency, directly affects the efficiency of livestock production. Here, this study was conducted to improve the boar sperm quality by using a non-thermal dielectric barrier discharge (DBD) plasma. Our results showed that DBD plasma exposure at 2.1 W for 15 s could improve boar sperm quality by increasing the exon methylation level of adenosine monophosphate-activated protein kinase (AMPK) and thus improving the glycolytic flux, mitochondrial function, and antioxidant capacity without damaging the integrity of sperm DNA and acrosome. In addition, DBD plasma could rescue DNA methyltransferase inhibitor decitabine-caused low sperm quality by reducing oxidative stress and mitochondrial damage. Therefore, the application of non-thermal plasma provides a new strategy for reducing sperm oxidative damage and improving sperm quality, which shows great potential in assisted reproduction to solve the problem of male infertility.

Keywords: non-thermal DBD plasma, sperm quality, AMPK methylation, energy metabolism, antioxidant capacity

Procedia PDF Downloads 9

Authors: Jae-Hyeon Kim, Michael Lee

Abstract:

Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

Procedia PDF Downloads 325

Authors: Sadaf Abbas, HimGauri Sabnis

Abstract:

Introduction: Peripartum cardiomyopathy is a rare but potentially life-threatening condition that presents as heart failure during the last month of pregnancy or within five months postpartum. The incidence of postpartum cardiomyopathy ranges from 1 in 1300 to 1 in 15,000 pregnancies. Risk factors include multiparty, advanced maternal age, multiple pregnancies, pre-eclampsia, and chronic hypertension. Study: A 30-year-old Para3+0 presented to the Emergency Department of St’Marry Hospital, Isle of Wight, on the seventh day postpartum, with acute shortness of breath (SOB), chest pain, cough, and a temperature of 38 degrees. The risk factors were smoking and class II obesity (BMI of 40.62). The patient had mild pre-eclampsia in the last pregnancy and was on labetalol and aspirin during an antenatal period, which was stopped postnatally. There was also a history of pre-eclampsia and haemolysis, elevated liver enzymes, low platelets (HELLP syndrome) in previous pregnancies, which led to preterm delivery at 35 weeks in the second pregnancy, and the first baby was stillborn at 24 weeks. On assessment, there was a national early warning score (NEWS score) of 3, persistent tachycardia, and mild crepitation in the lungs. Initial investigations revealed an enlarged heart on chest X-ray, and a CT pulmonary angiogram indicated bilateral basal pulmonary congestion without pulmonary embolism, suggesting fluid overload. Laboratory results showed elevated CRP and normal troponin levels initially, which later increased, indicating myocardial involvement. Echocardiography revealed a severely dilated left ventricle with an ejection fraction (EF) of 31%, consistent with severely impaired systolic function. The cardiology team reviewed the patient and admitted to the Coronary Care Unit. As sign and symptoms were suggestive of fluid overload and congestive cardiac failure, management was done with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), proton pump inhibitors, and supportive care. During admission, there was complications such as acute kidney injury, but then recovered well. Chest pain had resolved following the treatment. After being admitted for eight days, there was an improvement in the symptoms, and the patient was discharged home with a further plan of cardiac MRI and genetic testing due to a family history of sudden cardiac death. Regular appointment has been made with the Cardiology team to follow-up on the symptoms. Since discharge, the patient made a good recovery. A cardiac MRI was done, which showed severely impaired left ventricular function, ejection fraction (EF) of 38% with mild left ventricular dilatation, and no evidence of previous infarction. Overall appearance is of non-ischemic dilated cardiomyopathy. The main challenge at the time of admission was the non-availability of a cardiac radiology team, so the definitive diagnosis was delayed. The long-term implications include risk of recurrence, chronic heart failure, and, consequently, an effect on quality of life. Therefore, regular follow-up is critical in patient’s management. Conclusions: Peripartum cardiomyopathy is one of the cardiovascular diseases whose causes are still unknown yet and, in some cases, are uncontrolled. By raising awareness about the symptoms and management of this complication it will reduce morbidity and mortality rates and also the length of stay in the hospital.

Keywords: cardiomyopathy, cardiomegaly, pregnancy, puerperium

Procedia PDF Downloads 29

Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

Abstract:

The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

Procedia PDF Downloads 313

Authors: Sujata Sharma, Avinash Singh, Lovely Gautam, Pradeep Sharma, Mau Sinha, Asha Bhushan, Punit Kaur, Tej P. Singh

Abstract:

Peptidyl-tRNA hydrolase (Pth) Pth is an essential bacterial enzyme that catalyzes the release of free tRNA and peptide moeities from peptidyl tRNAs during stalling of protein synthesis. In order to design inhibitors of Pth from Pseudomonas aeruginosa (PaPth), we have determined the structures of PaPth in its native state and in the bound states with two compounds, amino acylate-tRNA analogue (AAtA) and 5-azacytidine (AZAC). The peptidyl-tRNA hydrolase gene from Pseudomonas aeruginosa was amplified by Phusion High-Fidelity DNA Polymerase using forward and reverse primers, respectively. The E. coliBL21 (λDE3) strain was used for expression of the recombinant peptidyl-tRNA hydrolase from Pseudomonas aeruginosa. The protein was purified using a Ni-NTA superflow column. The crystallization experiments were carried out using hanging drop vapour diffusion method. The crystals diffracted to 1.50 Å resolution. The data were processed using HKL-2000. The polypeptide chain of PaPth consists of 194 amino acid residues from Met1 to Ala194. The centrally located β-structure is surrounded by α-helices from all sides except the side that has entrance to the substrate binding site. The structures of the complexes of PaPth with AAtA and AZAC showed the ligands bound to PaPth in the substrate binding cleft and interacted with protein atoms extensively. The residues that formed intermolecular hydrogen bonds with the atoms of AAtA included Asn12, His22, Asn70, Gly113, Asn116, Ser148, and Glu161 of the symmetry related molecule. The amino acids that were involved in hydrogen bonded interactions in case of AZAC included, His22, Gly113, Asn116, and Ser148. As indicated by fittings of two ligands and the number of interactions made by them with protein atoms, AAtA appears to be a more compatible with the structure of the substrate binding cleft. However, there is a further scope to achieve a better stacking than that of O-tyrosyl moiety because it is not still ideally stacked. These observations about the interactions between the protein and ligands have provided the information about the mode of binding of ligands, nature and number of interactions. This information may be useful for the design of tight inhibitors of Pth enzymes.

Keywords: peptidyl tRNA hydrolase, Acinetobacter baumannii, Pth enzymes, O-tyrosyl

Procedia PDF Downloads 430

Authors: Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Pieter Van Der Vlies, Eelko Hak, Rolf M. F. Berger, Henk Groen, Bob Wilffert

Abstract:

Prenatal use of SRIs was previously associated with Congenital Heart Anomalies (CHA). The aim of the study is to explore whether pharmacogenetics plays a role in this teratogenicity using a gene-environment interaction study. A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs (paroxetine=3, fluoxetine=2, venlafaxine=1, paroxetine and venlafaxine=1) in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations in these ten genes. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). This study might be among the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, there were indications for a role of serotonin receptor polymorphisms in fetuses exposed to SRIs on fetal risk of CHA which warrants further investigation.

Keywords: gene-environment interaction, heart defects, pharmacogenetics, serotonin reuptake inhibitors, teratogenicity

Procedia PDF Downloads 219

Authors: Elisabetta Schievano, Valentina Zuccato, Claudia Finotello, Patricia Vit

Abstract:

Control of honey frauds is needed in Ecuador to protect bee keepers and consumers because simple syrups and new syrups with eucalyptus are sold as genuine honeys. Authenticity of Ecuadorian commercial honeys was tested with a vortex emulsion consisting on one volume of honey:water (1:1) dilution, and two volumes of diethyl ether. This method allows a separation of phases in one minute to discriminate genuine honeys that form three phase and fake honeys that form two phases; 34 of the 42 honeys analyzed from five provinces of Ecuador were genuine. This was confirmed with 1H NMR spectra of honey dilutions in deuterated water with an enhanced aminoacid region with signals for proline, phenylalanine and tyrosine. Classic quality indicators were also tested with this method (sugars, HMF), indicators of fermentation (ethanol, acetic acid), and residues of citric acid used in the syrup manufacture. One of the honeys gave a false positive for genuine, being an admixture of genuine honey with added syrup, evident for the high sucrose. Sensory analysis was the final confirmation to recognize the honey groups studied here, namely honey produced in combs by Apis mellifera, fake honey, and honey produced in cerumen pots by Geotrigona, Melipona, and Scaptotrigona. This is a valuable contribution to protect honey consumers, and to develop the beekeeping industry in Ecuador.

Keywords: fake, genuine, honey, 1H NMR, Ecuador

Procedia PDF Downloads 385

Authors: Srie Rezeki Nur Endah, Richa Mardianingrum

Abstract:

Cancer is one of the most feared diseases and is considered the leading cause of death worldwide. Generally, cancer drugs are synthetic drugs with relatively more expensive prices and have harmful side effects, so many people turn to traditional medicine, for example by utilizing herbal medicine. Erythrina poeppigiana is one of the plants that can be used as a medicinal plant containing 10,11-dihidroerisodin compounds that are useful anticancer etnofarmakologi. The purpose of this study was to identify the target of 10,11 dihydroerisodin receptor compound as in silico anticancer candidate. The pure isolate was tested physicochemically by MS (Mass Spectrometry), UV-Vis (Ultraviolet – Visible), IR (Infra Red), 13C-NMR (Carbon-13 Nuclear Magnetic Resonance), 1H-NMR (Hydrogen-1 Nuclear Magnetic Resonance), to obtain the structure of 10,11-dihydroerisodin alkaloid compound then identified to target receptors in silico. From the results of the study, it was found that 10,11-dihydroerisodin compound can work on the Serine / threonine-protein kinase Chk1 receptor that serves as an anti-cancer candidate.

Keywords: anti-cancer, Erythrina poeppigiana, target receptor, 10, 11- dihidroerisodin

Procedia PDF Downloads 246

Authors: Muhammad Arifur Rahman, Talukdar M. Waliullah, Takashi Ushimaru

Abstract:

Nucleophagy selectively degrades nuclear materials, especially nucleolus after nutrient starvation or inactivation of TORC1 kinase in budding yeast. Budding yeast phosphatidate (PA) phosphatase Pah1 that converts PA to diacylglycerol is essential for partitioning of lipid precursors between membrane and storage that is crucial for many aspects of cell growth and development. Pah1 is required for nuclear/ER membrane biogenesis and vacuole function, but whether Pah1 and its activator Nem1/Spo7 protein phosphatase complex are involved in autophagy is largely unknown. Loss of Pah1 causes expansion of the nucleus and fragmentation of the vacuole. Here we show that Pah1 is required for bulk autophagy and nucleophagy after TORC1 inactivation. Loss of Pah1 impaired nucleophagy severely and bulk autophagy to a lesser extent. Loss of the Pah1 activator Nem1-Spo7 protein phosphatase exhibited similar features.

Keywords: autophagy, Nem1/Spo7 phosphatase, Pah1, nucleophagy, TORC1

Procedia PDF Downloads 227

Authors: Yuping Liu, Li Tao, Yin Lu

Abstract:

Accumulating evidence has been shown that diallyl trisulfide (DATS) from garlic may reduce the risk of developing several types of cancer. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we demonstrate the effectiveness of DATS on the metastatic behaviors of MDA-MB-435s human breast cancer cell line co-incubated with activated platelets. Indeed, our data identified that DATS significantly blocked platelets fouction induced by PAF, followed by the decreased production of TXB2. DATS was found to dose-dependently suppressed MDA-MB-435s cell migration and invasion in presence of activated platelets by PAF in vitro. Furthermore, the expression, secretion and enzymatic activity of matrix metalloproteinase (MMP)-2/9, as well as the luciferase activity of upstream regulator NF-κB in MDA-MB-435s, were obviously diminished by DATS. In parallel, DATS blocked upstream NF-κB activation signaling complexes composed of extracellular signal-related kinase (ERK) as assessed by measuring the levels of the phosphorylated forms.

Keywords: DATS, ERK, metastasis, MMPs, NF-κB, platelet

Procedia PDF Downloads 386

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 191

Authors: Vita Strazdina, Aleksandrs Jemeljanovs, Vita Sterna

Abstract:

Not all proteins have the same nutritional value, since protein quality strongly depends on its amino acid composition and digestibility. The meat of game animals could be a high protein source because of its well-balanced essential amino acids composition. Investigations about biochemical composition of game meat such as wild boar (Sus scrofa scrofa), roe deer (Capreolus capreolus) and beaver (Castor fiber) are not very much. Therefore, the aim of the investigation was evaluate protein composition of game meat hunted in Latvia. The biochemical analysis, evaluation of connective tissue and essential amino acids in meat samples were done, the amino acids score were calculate. Results of analysis showed that protein content 20.88-22.05% of all types of meat samples is not different statistically. The content of connective tissue from 1.3% in roe deer till 1.5% in beaver meat allowed classified game animal as high quality meat. The sum of essential amino acids in game meat samples were determined 7.05–8.26g100g-1. Roe deer meat has highest protein content and lowest content of connective tissues among game meat hunted in Latvia. Concluded that amino acid score for limiting amino acids phenylalanine and tyrosine is high and shows high biological value of game meat.

Keywords: dietic product, game meat, amino acids, scores

Procedia PDF Downloads 321

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

Abstract:

Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

Procedia PDF Downloads 276

Authors: Muhammad Qamar Masood, Syed Abbas Raza, Umar Yousaf Raja, Imran Hassan, Bilal Afzal, Muhammad Aleem Zahir, Atika Shaheer

Abstract:

Background: Cardiovascular disease (CVD) is a major burden among people with type 2 diabetes (T2D) with 1 in 3 reported to have CVD. Therefore, understanding real-world clinical characteristics and prescribing patterns could help in better care. Objective: The CONVERGE (Cardiovascular Outcomes and Value in the Real world with GLP-1RAs) study characterized demographics and medication usage patterns in T2D intensified (add-on to metformin) overall population. The data were further divided into subgroups {dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), insulins, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is)}, according to the latest prescribed antidiabetic agent (ADA) in India/Pakistan/Thailand. Here, we report findings from Pakistan. Methods: A multi-center retrospective study utilized data from medical records between 13-Sep-2008 (post-market approval of GLP-1RAs) and 31-Dec-2017 in adults (≥18-year-old). The data for this study were collected from 05 centers / institutes located in major cities of Pakistan, including Karachi, Lahore, Islamabad, and Multan. These centers included National Hospital, Aga Khan University Hospital, Diabetes Endocrine Clinic Lahore, Shifa International Hospital, Mukhtar A Sheikh Hospital Multan. Data were collected at start of medical record and at 6 or 12-months prior to baseline based on variable type; analyzed descriptively. Results: Overall, 1,010 patients were eligible. At baseline, overall mean age (SD) was 51.6 (11.3) years, T2D duration was 2.4 (2.6) years, HbA1c was 8.3% (1.9) and 35% received ≥1CVD medications in the past 1-year (before baseline). Most frequently prescribed ADAs post-metformin were DPP-4is and SUs (~63%). Only 6.5% received GLP-1RAs and SGLT-2is were not available in Pakistan during the study period. Overall, it took a mean of 4.4 years and 5 years to initiate GLP-1RAs and SGLT-2is, respectively. In comparison to other subgroups, more patients from GLP-1RAs received ≥3 types of ADA (58%), ≥1 CVD medication (64%) and had higher body mass index (37kg/m2). Conclusions: Utilization of GLP-1RAs and SGLT-2is was low, took longer time to initiate and not before trying multiple ADAs. This may be due to lack of evidence for CV benefits for these agents during the study period. The planned phase 2 of the CONVERGE study can provide more insights into utilization and barriers to prescribe GLP-1RAs and SGLT-2is post 2018 in Pakistan.

Keywords: type 2 diabetes, GLP-1RA, treatment intensification, cardiovascular disease

Procedia PDF Downloads 60

Authors: Ayat Bani Rashaid, Zain Khasawneh, Mazin Alqhazo, Shreen Nusair, Mohammad El-Khateeb, Mahmoud Bashtawi

Abstract:

Autism Spectrum disorder (ASD) is a psychiatric disorder with unknown etiology that mainly affects children in the first three years of life. Alterations of amino acid levels are believed to contribute to ASD. The levels of six essential amino acids (methionine, histidine, valine, leucine, threonine, and phenylalanine), five conditional amino acids (proline, tyrosine, glutamine, cysteine, and cystine), and five non-essential amino acids (asparagine, aspartic acid, alanine, serine, and glutamic acid) in hair samples of children with ASD (n = 25) were analyzed and compared to corresponding levels in healthy age-matched controls (n = 25). The results showed that the levels of methionine, alanine, and asparagine were significantly lower in the hair samples of ASD group compared to those of the control group (p ≤ 0.05). However, the levels of glutamic acid were significantly higher in the ASD group than the control group (p ≤ 0.05). The current findings could contribute towards further understanding of ASD etiology and provide specialists with a hair amino acid profile utilized as a biomarker for early diagnosis of ASD. Such biomarkers could participate in future developments of therapies that reduce ASD-related symptoms.

Keywords: autism spectrum disorder, amino acids, liquid chromatography-tandem mass spectrometry, human hair

Procedia PDF Downloads 138

Authors: Razieh Niazmand, Dina Sadat Mousavian, Parvin Sharayei

Abstract:

This study investigated the effect of carboxymethyl cellulose (CMC), tragacanth, and saalab hydrocolloids in two concentrations (0.3%, 0.7%) and different frying media, refined canola oil (RCO), RCO + 1% bene kernel oil (BKO), and RCO + 1 mg/l unsaponifiable matter (USM) of BKO on acrylamide formation in fried potato slices. The hydrocolloid coatings significantly reduced acrylamide formation in potatoes fried in all oils. Increasing the hydrocolloid concentration from 0.3% to 0.7% produced no effective inhibition of acrylamide. The 0.7 % CMC solution was identified as the most promising inhibitor of acrylamide formation in RCO oil, with a 62.9% reduction in acrylamide content. The addition of BKO or USM to RCO led to a noticeable reduction in the acrylamide level in fried potato slices. The findings suggest that a 0.7% CMC solution and RCO+USM are promising inhibitors of acrylamide formation in fried potato products.

Keywords: CMC, frying, potato, saalab, tracaganth

Procedia PDF Downloads 288

Authors: Oseyemi O. Olubomehin, Edith O. Ajaiyeoba, Kio A. Abo, Eleonora D. Goosen

Abstract:

Diabetes is a major degenerative disease of global concern and it is the third most lethal disease of mankind, accounting for about 3.2 million deaths annually. Lowering postprandial hyperglycemia by inhibition of carbohydrate hydrolyzing enzyme such as alpha-amylase is one of the therapeutic approaches to treat Type 2 Diabetes. Alpha-amylase inhibitors from plants have been found to be effective in managing postprandial hyperglycemia. In continuation of our anti-diabetic activities of this plant, bioassay-guided fractionation and isolation using 0.1-1.0 mg/mL furnished djalonenol, a monoterpene diol with a significant 53.7% α-amylase inhibition (p<0.001) from the stem bark which was comparable to acarbose which gave a 54.9% inhibition. Spectral characterization using Infra-red, Gas Chromatogrphy-Mass spectrometry, 1D and 2D NMR of the isolated compound was done to elucidate the structure of the compound.

Keywords: alpha-amylase inhibitor, hyperglycemia, postprandial, diabetes

Procedia PDF Downloads 458

Authors: S. M. Satyam, K. L. Bairy, R. Pirasanthan, R. L. Vaishnav

Abstract:

Zincovit tablets have been used as nutritional food supplement over a prolonged period of time. The aim of the present study was to investigate the cardio-protective effect of combined formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg) using a Langendorff model of ischemia-reperfusion in Wistar rats. Following 21 days of pre-treatment, combined formulation of grape seed extract and Zincovit tablets significantly attenuated ischemia-reperfusion induced cardiac injury in terms of increased coronary flow rate (p < 0.01), decreased creatine kinase activity in coronary effluent (p < 0.05), decreased MDA (p < 0.001), 4-HNE (p < 0.001) and increased protein thiol content (p < 0.01) in comparison with the untreated (control) group. This study opens an avenue to clinical studies to demonstrate the validity of this paradigm as a nutritional food supplement, which could improve the clinical outcome of patients subjected to percutaneous angioplasty.

Keywords: grape seed extract, myocardial ischemia-reperfusion injury, oxidative stress, Zincovit tablets

Procedia PDF Downloads 376

Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

Abstract:

Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

Procedia PDF Downloads 79