Search results for: binding inhibitor

Authors: Rafenomananjara Tsinjo Nirina, Tomoo Sekito, Andrianaivoravelona Jaconnet Oliva

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Manufacturing a composite material from post-consumer bottles is an interesting outlet since Madagascar is still facing the challenges of managing plastic waste on the one hand and appropriate waste treatment facilities are not yet developed on the other hand. New waste management options are needed to divert End-Of-Life (EOL) soft plastic wastes from landfills and incineration. Waste polyethylene terephthalate (PET) bottles might be considered as a valuable resource and recovered into polymer concrete. The methodology is easy to implement and appropriate to the local context in Madagascar. This approach will contribute to the production of ecological building materials that might be profitable for the environment and the construction sector. This work aims to study the feasibility of using the post-consumer PET bottles as an alternative binding agent instead of the conventional Portland cement and water. Then, the mechanical and physical properties of the materials were evaluated.

Keywords: PET recycling, polymer concrete, ecological building materials, pollution mitigation

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Authors: A. Khosrozadeh, M. A. Darabi, M. Xing, Q. Wang

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Fabrication of a high-performance supercapacitor (SC) using a flexible cellulose-based composite film of polyaniline (PANI), reduced graphene oxide (RGO), and silver nanowires (AgNWs) is reported. The flexibility, high capacitive behaviour, and cyclic stability of the entire device make it a good candidate for wearable SCs. The results show that a capacitance as high as 73.4 F/g (1.6 F/cm2) at a discharge rate of 1.1 A/g is achieved by the device. In addition, the SC demonstrates a power density up to 468.8 W/kg and an energy density up to 5.1 wh/kg. The flexibility of the composite film is attributed to the binding effect of cellulose fibers as well as reinforcing effect of AgNWs. The excellent electrochemical performance of the device is found to be owing to the synergistic effect between PANI/RGO/AgNWs ternary in a cushiony cellulose matrix and porous structure of the composite.

Keywords: cellulose, polyaniline, reduced graphene oxide, silver, super capacitor

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Authors: Ilma Robo, Saimir Heta, Edona Hasanaj, Vera Ostreni

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The hybrid layer, the way it is created and how it is protected against degradation over time, is the key to the clinical success of a composite restoration. The composite supports the dentinal structure exactly with the realized surface of microretension. Thus, this surface is in direct proportion to its size versus the duration of clinical use of composite dental restoration. Micro-retention occurs between dentin or acidified enamel and adhesive resin extensions versus pre-prepared spaces, such as hollow dentinal tubules. The way the adhesive resin binds to the acidified dentinal structure depends on the physical or chemical factors of this interrelationship between two structures with very different characteristics. During the acidification process, a precursor to the placement of the adhesive resin layer, activation of metaloproteinases of dental origin occurs, enzymes which are responsible for the degradation of the hybrid layer. These enzymes have expressed activity depending on the presence of Zn2 + or Ca2 + ions. There are several ways to inhibit these enzymes, and consequently, there are several ways to inhibit the degradation process of the hybrid layer. The study aims to evaluate chlorhexidine as a solution element, inhibitor of dentin activated metalloproteinases, as a result of the application of acidification. This study aims to look at this solution in advantage or contraindication theories, already published in the literature.

Keywords: hybrid layer, chlorhexidine, degradation, application

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Authors: A. Bhartiya, S. Botchway, M. Yusuf, I. Robinson

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Chromatin condensation is maintained by DNA-based proteins and some divalent cations (Mg²⁺, Ca²⁺, etc.). Condensation process during cell division maintains structural and functional organizations of chromosomes by transferring genetic information correctly to daughter cells. Fluorescence Lifetime Imaging (FLIM) technique measures the fluorescence decay of fixed human chromosomes by calculating the lifetime of fluorophores at a pixel x of the arrival of each photon as a function of time delay t, following excitation with a laser pulse. Fixed metaphase human chromosomes were labelled with DNA-binding dye, DAPI and later DAPI fluorescence lifetime measured using multiphoton microscopy. 5 out of 23 pairs of human chromosomes shown shorter lifetime at the centromere region, differentiating proportion of compaction along the length of chromosomes. Different lifetime was observed in a condensed and de-condensed chromosome. It clearly indicates the involvement of divalent cations in the process of condensation.

Keywords: divalent cations, FLIM (Fluorescence Lifetime Imaging), human chromosomes, multiphoton microscopy

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Authors: Dalia Jomehpour, Sara Sheikhlary, Esmaeil Heydari, Mohammad Hossien Majles Ara

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In this study, we report fulvic acid-coated iron oxide nanoparticles of 10.7 ± 2.7 nm size, which serve to inhibit amyloid fibrillation formation. Although the effect of fulvic acid on tau fibrils was investigated, to our best knowledge, its inhibitory impacts on amyloid aggregation formation have been assessed neither in-vitro nor in-vivo. On the other hand, iron oxide nanoparticles exhibit anti-amyloid activity on their own. This study investigates the inhibitory effect of fulvic acid coated iron oxide nanoparticles on amyloid aggregations formed from the commonly used in-vitro model, lysozyme from chicken egg white. FESEM, XRD, and FTIR characterization confirmed that fulvic acid was coated onto the surface of the nanoparticles. The inhibitory effects of the fulvic acid coated iron oxide nanoparticles were verified by Thioflavin T assay, circular dichroism (CD), and FESEM analysis. Furthermore, the toxicity of the nanoparticles on the neuroblastoma SH-SY5Y human cell line was assessed through an MTT assay. Our results indicate that fulvic acid coated iron oxide nanoparticles can efficiently inhibit the formation of amyloid aggregations while exhibiting negligible in-vitro toxicity; thus, they can be used as anti-amyloid agents in the development of the potential drug for neurodegenerative diseases.

Keywords: Alzheimer’s disease, fulvic acid coated iron oxide nanoparticles, fulvic acid, amyloid inhibitor, polyphenols

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Authors: Milad Zoghi, M. Zahangir Kabir

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Performance of armchair graphene nanoribbon (AGNR) resonant tunneling diodes (RTD) alter if they go under strain. This may happen due to either using stretchable substrates or real working conditions such as heat generation. Therefore, it is informative to understand how mechanical deformations such as uniaxial strain can impact the performance of AGNR RTDs. In this paper, two platforms of AGNR RTD consist of width-modified AGNR RTD and electric-field modified AGNR RTD are subjected to both compressive and tensile uniaxial strain ranging from -2% to +2%. It is found that characteristics of AGNR RTD markedly change under both compressive and tensile strain. In particular, peak to valley ratio (PVR) can be totally disappeared upon strong enough strain deformation. Numerical tight binding (TB) coupled with Non-Equilibrium Green's Function (NEGF) is derived for this study to calculate corresponding Hamiltonian matrices and transport properties.

Keywords: armchair graphene nanoribbon, resonant tunneling diode, uniaxial strain, peak to valley ratio

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Shilpa K. Nandwani, Mousumi Chakraborty, Smita Gupta

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When selecting surfactants for surfactant flooding during enhanced oil recovery, the most important criteria is that the surfactant system should reduce the interfacial tension between water and oil to ultralow values. In the present study, a mixture of ionic liquid surfactant and commercially available binding agent sodium tosylate has been used as a surfactant mixture. Presence of wormlike micelles indicates the possibility of achieving ultralow interfacial tension. Surface tension measurements of the mixed surfactant system have been studied. The emulsion size distribution of the mixed surfactant system at varying salinities has been studied. It has been found that at high salinities the viscoelastic surfactant system loses their efficacy and degenerate. Hence the given system may find application in low salinity reservoirs, providing good mobility to the flood during tertiary oil recovery process.

Keywords: ionic liquis, interfacial tension, Na-tosylate, viscoelastic surfactants

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: Juneseok You, Chanho Park, Kuehwan Jang, Sungsoo Na

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Sensing of nanotoxic materials is strongly important, as their engineering applications are growing recently and results in that nanotoxic material can harmfully influence human health and environment. In current study we report the quartz crystal microbalance (QCM)-based, in situ and real-time sensing of nanotoxic-material by frequency shift. We propose the in situ detection of nanotoxic material of zinc oxice by using QCM functionalized with a taget-specific DNA. Since the mass of a target material is comparable to that of an atom, the mass change caused by target binding to DNA on the quartz electrode is so small that it is practically difficult to detect the ions at low concentrations. In our study, we have demonstrated the in-situ and fast detection of zinc oxide using the quartz crystal microbalance (QCM). The detection was derived from the DNA hybridization between the DNA on the quartz electrode. The results suggest that QCM-based detection opens a new avenue for the development of a practical water-testing sensor.

Keywords: nanotoxic material, qcm, frequency, in situ sensing

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Authors: Debajit Kalita, Macmillan Nongkhlaw, S. R. Joshi

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Mercury (Hg) is a highly toxic heavy metal released both from naturally occurring volcanoes and anthropogenic activities like alkali and mining industries as well as biomedical wastes. Exposure to mercury is known to affect the nervous, gastrointestinal and renal systems. In the present study, a bacterial isolate identified using 16S rRNA marker as Paenibacillus jamilae PKR1 isolated from India’s largest sandstone-type uranium deposits, containing an average of 0.1% U3O8, was found to be resistance to Hg contamination under culture conditions. It showed strong hydrophobicity as revealed by SAT, MATH, PAT, SAA adherence assays. The Fourier Transform Infrared (FTIR) spectra showed the presence of hydroxyl, amino and carboxylic functional groups on the cell surface EPS which are known to contribute in the binding of metals. It is proposed that the characterized isolate tolerating up to 4.0mM of mercury provides scope for its application in bioremediation of mercury from contaminated sites.

Keywords: mercury, Domiasiat, uranium, paenibacillus jamilae, hydrophobicity, FTIR

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Authors: N. Yang, R. Linforth, I. Fisk

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The influence of food processing and choice of flavour solvent was investigated using biscuits prepared with vanillin flavour as an example. Powder vanillin either was added directly into the dough or dissolved into flavour solvent then mixed into the dough. The impact of two commonly used flavour solvents on food quality was compared: propylene glycol (PG) or triacetin (TA). The analytical approach for vanillin detection was developed by chromatography (HPLC-PDA), and the standard extraction method for vanillin was also established. The results indicated the impact of solvent choice on vanillin level during biscuit preparation. After baking, TA as a more heat resistant solvent retained more vanillin than PG, so TA is a better solvent for products that undergo a heating process. The results also illustrated the impact of mixing and baking on vanillin stability in the matrices. The average loss of vanillin was 33% during mixing and 13% during baking, which indicated that the binding of vanillin to fat or flour before baking might cause larger loss than evaporation loss during baking.

Keywords: biscuit, flavour stability, food quality, vanillin

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Authors: Zhongyang Sun, Shu Zhang, Manjiang Xie

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Emerging evidence indicates that microRNAs (miRNAs) play important roles in modulating osteoblast function and bone formation. However, the influence of miRNA on osteoblast proliferation and the possible mechanisms underlying remain to be defined. In this study, we aimed to investigate whether miR-103 regulates osteoblast proliferation under simulated microgravity condition through regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium channels (LTCCs). We first investigated the effect of simulated microgravity on osteoblast proliferation and the outcomes clearly demonstrated that the mechanical unloading inhibits MC3T3-E1 osteoblast-like cells proliferation. Using quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was up-regulated in response to simulated microgravity. In addition, we observed that up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted osteoblast proliferation under simulated microgravity condition. Furthermore, knocking-down or over-expressing miR-103, respectively, up- or down-regulated the level of Cav1.2 expression and LTCCs currents, suggesting that miR-103 acts as an endogenous attenuator of Cav1.2 in osteoblasts under the condition of simulated microgravity. More importantly, we showed that the effect of miR-103 on osteoblast proliferation was diminished in simulated microgravity, when co-transfecting miR-103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2 expression under simulated microgravity condition. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblast, identifying miR-103 as a novel possible therapeutic target in bone remodeling disorders in this mechanical unloading.

Keywords: microRNA, osteoblasts, cell proliferation, Cav1.2, simulated microgravity

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Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

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Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

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Authors: Katarzyna Kamińska

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When thinking about custodial arrangements after divorce or separation, there has been a shift from sole custody, particularly maternal preference, to joint physical custody. In many Western countries, an increasing of children with separated parents have joint physical custody, which is believed to be in the best interests of the child, as children can maintain personal relations and direct contact with both parents on a regular basis. The aim of the article is to examine joint physical custody, both from the perspective of the binding legal instruments that are relevant to joint physical custody, the Principles of European Family Law drafted by the CEFL, as well as the international research on this matter. The thesis underlying this paper is that joint physical custody is in itself neither good nor bad, and it depends on how the arrangements are managed by the parents. The paper includes a reflection on joint physical custody in the face of the COVID-19 crisis. The results indicate that in normal circumstances, joint physical custody demands broad communication, and now it times of crisis, we need over-communication about children and plans. Only a very tight and coordinated co-parenting plan make the whole family safer.

Keywords: joint physical custody, co-parenting, child welfare, COVID-19

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Authors: Yen-Ni Teng, Hsing-Yi Chen, Hsien-An Pan, Yung-Ming Lin, Hany A. Omar, Jui-Hsiang Hung

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Leucine-rich repeats and WD repeat domain containing 1 (LRWD1) is highly expressed in the testes of healthy males. On the other hand, LRWD1 is significantly down-regulated in the testicular tissues of patients with severe spermatogenic defects. In our study, the downregulation of LRWD1 expression by shRNA caused a significant reduction of cell growth and mitosis and a noteworthy increase in the cell microtubule atrophy rate. Here, we used EMBOSS CpG plot analysis to explore the promoter region of LRWD1 gene. We found that CpG islands are located between positions -253 to +5 nucleotides upstream from the LRWD1 transcription start site. Luciferase reporter assay revealed that the hypermethylation of the LRWD1 promoter reduced the transcription activity in cells. In addition, quantitative methylation-specific PCR and immunostaining showed that the methylation inhibitor, 5-Aza-2'-deoxycytidine, increased LRWD1 promoter activity, LRWD1 mRNA, protein expression and cell viability. Whereas, the methylation activator, S-adenosylmethionine, caused opposite effects. The overexpression of p53 and Nrf2 in NT2/D1 cells increased LRWD1 promoter activity while 5-fluorodeoxyuridine decreased it. In conclusion, this study highlights evidence that the methylation status of LRWD1 promoter is associated with LRWD1 expression. Since the expression level of LRWD1 plays an important role in spermatogenesis, the methylation status of LRWD1 may serve as a novel molecular diagnostic or therapeutic approach in male's infertility.

Keywords: LRWD1, DNA methylation, p53, Nrf2

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Authors: Annabelle Onyefulu-Kingston

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One of the major purposes of AI today is to evaluate and analyze millions of micro and macro data in order to determine what is relevant in a particular case and proffer it in an adequate manner. Microdata, as far as it relates to AI in international arbitration, is the millions of key issues specifically mentioned by either one or both parties or by their counsels, arbitrators, or arbitral tribunals in arbitral proceedings. This can be qualifications of expert witness and admissibility of evidence, amongst others. Macro data, on the other hand, refers to data derived from the resolution of the dispute and, consequently, the final and binding award. A notable example of this includes the rationale of the award and specific and general damages awarded, amongst others. This paper aims to critically evaluate and analyze the possibility of technological inclusion in international arbitration. This research will be imploring the qualitative method by evaluating existing literature on the consequence of applying AI to both micro and macro data in international arbitration, and how this can be of assistance to parties, counsels, and arbitrators.

Keywords: AI-based technologies, algorithms, arbitrators, international arbitration

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Authors: S. S. Patil, R. M. Mhetre, S. V. Patil

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Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and heart failure in prophylactic treatment after myocardial infarction and in diabetic nephropathy. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of lisinopril by formulating intranasal microspheres with Carbopol 974P NF and HPMC K4 M along with film forming polymer ethyl cellulose.The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, ex vivo mucoadhesion, drug release, ex vivo diffusion studies. All formulations has shown entrapment efficiency between 80 to more than 95%, mucoadhesion was more than 80 % and drug release up to 90 %. Ex vivo studies revealed tht the improved bioavailability of drug compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres shown better results than single carbopol based microspheres for the delivery of lisinopril.

Keywords: microspheres, lisinopril, nasal delivery, solvent evaporation method

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Ben Amar Cheba, Taha Ibrahim Zaghloul, Mohamad Hisham El-Massry, Ahmad Rafik El-Mahdy

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Seventy two bacterial strains with ability to degrade chitin were isolated during a screening program. One of the most potent isolates (strain R2) was identified as Bacillus sp. using conventional methods as well as 16S rRNA technique and submitted in the Gen Bank sequence database as Bacillus sp. R2 with a given accession number DQ 923161. This strain was able to produce high levels of extracellular chitinase. The chitinase of Bacillus sp. R2 hydrolyzed several chitinous substrates preferentially and showed a maximum activity toward the β chitin such as Calmar pen and squid bone chitins with the folds 1.47 and 1.23 respectively. The enzyme also exhibited a substrate binding capacity of more than 70% for squid chitin, shrimp shell colloidal chitin, chitosan and prawn shell chitin. The chitinase showed a moderate antifungal activity against many phytopathogenic fungi such as Aspergillus niger, A. flavus, Penicillium degitatum and Fusarium calmorum.This strain could be a suitable candidate for chitinase production on an industrial scale for using as promising antifungal biopestecide.

Keywords: antifungal activity, Bacillus sp. R2, chitinase, substrate specificity

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Authors: Gulcan Sahal, Nermin Hande Avcioglu, Isil Seyis Bilkay

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Klebsiella species which are natural colonizers of human upper respiratory and human gastrointestinal tracts are also responsible for every reoccurring nosocomial infections by means of having ability to form slimy layers known as biofilm on many surfaces. Therefore, in this study, investigation of biofilm formation in K. pneumoniae and K. rhinoscleromatis and examination of each Klebsiella strains’ clinical information in the light of their biofilm formation results were aimed. In this respect, biofilm formation of Klebsiella strains was analyzed via crystal violet binding assay. According to our results, biofilm formation levels of K. pneumoniae and K. rhinoscleromatis strains were different from each other. Additionally, in comparison to K. rhinoscleromatis strains, K. pneumoniae was observed to include higher amounts of strong biofilm forming strains. Besides, it was also seen that clinical information of patients from which strong biofilm forming Klebsiella strains were isolated were similar to each other. Our results indicate that there should be more precautions against K. pneumoniae which includes higher amount of strong biofilm forming strains.

Keywords: biofilm formation, Klebsiella pneumoniae, Klebsiella rhinoscleromatis, biosystems engineering

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Md. Samsuddin Ansari, Ashish Arora

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Every year 10 million people fall ill with one of the oldest diseases known as tuberculosis, caused by Mycobacterium tuberculosis. The success of M. tuberculosis as a pathogen is because of its ability to persist in host tissues. Multidrug resistance (MDR) mycobacteria cases increase every day, which is associated with efflux pumps controlled at the level of transcription. The transcription regulators of MDR transporters in bacteria belong to one of the following four regulatory protein families: AraC, MarR, MerR, and TetR. Phenolic acid decarboxylase repressor (PadR), like a family of transcription regulators, is closely related to the MarR family. Phenolic acid decarboxylase repressor (PadR) was first identified as a transcription factor involved in the regulation of phenolic acid stress response in various microorganisms (including Mycobacterium tuberculosis H37Rv). Recently research has shown that the PadR family transcription factors are global, multifunction transcription regulators. Rv0047c is a PadR subfamily-1 protein. We are exploring the biophysical and structural characterization of Rv0047c. The Rv0047 gene was amplified by PCR using the primers containing EcoRI and HindIII restriction enzyme sites cloned in pET-NH6 vector and overexpressed in DH5α and BL21 (λDE3) cells of E. coli following purification with Ni2+-NTA column and size exclusion chromatography. We did DSC to know the thermal stability; the Tm (transition temperature) of protein is 55.29ºC, and ΔH (enthalpy change) of 6.92 kcal/mol. Circular dichroism to know the secondary structure and conformation and fluorescence spectroscopy for tertiary structure study of protein. To understand the effect of pH on the structure, function, and stability of Rv0047c we employed spectroscopy techniques such as circular dichroism, fluorescence, and absorbance measurements in a wide range of pH (from pH-2.0 to pH-12). At low and high pH, it shows drastic changes in the secondary and tertiary structure of the protein. EMSA studies showed the specific binding of Rv0047c with its own 30-bp promoter region. To determine the effect of complex formation on the secondary structure of Rv0047c, we examined the CD spectra of the complex of Rv0047c with promoter DNA of rv0047. The functional role of Rv0047c was characterized by over-expressing the Rv0047c gene under the control of hsp60 promoter in Mycobacterium tuberculosis H37Rv. We have predicted the three-dimensional structure of Rv0047c using the Swiss Model and Modeller, with validity checked by the Ramachandra plot. We did molecular docking of Rv0047c with dnaA, through PatchDock following refinement through FireDock. Through this, it is possible to easily identify the binding hot-stop of the receptor molecule with that of the ligand, the nature of the interface itself, and the conformational change undergone by the protein pattern. We are using X-crystallography to unravel the structure of Rv0047c. Overall the studies show that Rv0047c may have transcription regulation along with providing an insight into the activity of Rv0047c in the pH range of subcellular environment and helps to understand the protein-protein interaction, a novel target to kill dormant bacteria and potential strategy for tuberculosis control.

Keywords: mycobacterium tuberculosis, phenolic acid decarboxylase repressor, Rv0047c, Circular dichroism, fluorescence spectroscopy, docking, protein-protein interaction

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Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

Abstract:

Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

Procedia PDF Downloads 104

Authors: Galina Mamardashvili, Nugzar Mamardashvili, Win Dehaen

Abstract:

The processes of complexation of the Zn-tetraarylporphyrins with eight 4-(4-(3,6-bis(t-butyl)carbazol-9-yl-phenyl)-1,2,3-triazole (ZnP1) and eight 4-(4-(3,6-di-tert-butyl-9-H-carbazol-9-yl)phenoxy)methyl)-2,4,6-trimethylphenyl (ZnP2)with the 1,10-diaza-4,7,13,18tetraoxabicyclo[8.5.5]eicosane (L1),1,10-diaza-4,7,13,16,21,24-hexaoxabicyclo[8.8.8]hexacosane (L2)and 1,10-diaza-5,6,14,15-dibenzo-4,7,13,16,21,24 hexaoxabicyclo[8.8.8] hexacosane (L3) were investigated by the method of spectrophotometric titration and ¹H NMR-spectroscopy. We determined the structures of the host-guest complexes, and their stability constants in toluene were calculated. It was found out that the ZnP1 interacts with the guest molecules L1, L2 with the formation of stable "nest" type complexes and does not form similar complexes with the L3 (presumably due to the fact that the L3 does not match the size of the porphyrin ZnP(1) cavity). On the other hand, the porphyrin ZnP2 binds all of the ligands L1-L3, however complexes thus formed are less stable than complexes ZnP1-L1, ZnP1-L2. In the report, we will also discuss the influence of the alkali cations additives on the stability of the complexes between the porphyrin ZnP1, ZnP2 hosts and guest molecules of the ligands L1-L3.

Keywords: porphyrin, cryptand, cation, complex guest-host

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Authors: Dandan Shen, Hui-zhu Wang, Xi Yu, LiLi Gui, Xiao Wei, Xiao-yan Jiang, Da-wei Wang, Min Hong

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Yu-ping-feng-san (YPFS) is a clinical medicine for asthma and other allergic diseases, but the mechanism of YPFS on relapse of allergy is unclear. Currently, people come to realize the epithelial cells(EC) play a key role in stimulating and regulating local immune response. The study of thymic stromal lymphopoietin（TSLP derived from EC provides an important evidence that the EC can regulate immune response to stimulate allergic response. In this study, we observed the effect of YPFS on TSLP in vivo and in vitro. We established a method by using bronchial epithelial cells (16HBE) for screening potential bioactive components by HPLC-MS in YPFS and then analyzed the components in serum containing YPFS by UPLC-MS. The results showed that YPFS could decrease TSLP protein level in OVA-sensitized mice and 16HBE cells. Five components combing with the 16HBE cells were both detected in the serum.

Keywords: TSLP, bronchial epithelial cells, cell-binding, drug-containing serum

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Authors: Marcela Dvorakova, Lenka Langhansova, Premysl Landa

Abstract:

A series of quinazoline derivatives bearing aromatic rings in 2- and 4-positions were prepared and tested for their biological activity. Firstly, the compounds were evaluated for their potential to inhibit various kinases, such as autophagy activating kinase ULK1, 3-Phosphoinositide-dependent kinase 1, and TANK-binding kinase 1. None of the compounds displayed any activity on these kinases. Secondly, the compounds were tested for their anti-inflammatory activity expressed as cyclooxygenase (COX) isoforms and 5-lipoxygenase (5-LOX) inhibition. Three of the compounds showed significant selectivity towards COX-1 isoform (COX-2/COX-1 SI = 20-30). They inhibited COX-1 in a single-digit µM range. There was also one compound that exhibited inhibitory activity towards all three tested enzymes in µM range (IC50COX-1 = 1.9 µM; IC50COX-2 and 5-LOX = 10.1µM. COX-1 inhibition was until recently considered undesirable due to COX-1 constitutive expression in most cell types and tissues. Thus, there are not many compounds known with selective COX-1 activity. However, it is now believed that COX-1 plays an important role in the pathophysiology of several acute and chronic disorders, including cancer or neurodegenerative diseases. Thus, the discovery of effective COX-1 selective inhibitors is desirable and important.

Keywords: cyclooxygenases, kinases, lipoxygenases, quinazolines

Procedia PDF Downloads 135

Authors: Ram Narayan Khare, Aradhna Shrivastava, Adhyatma Khare

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This paper focuses on the damage that has been occurred in the Ancient structures due to various factors such as rainfall, climate, insects, lifespan and also most important lack of technologies in the era of its construction. The structure is of lime surkhi masonry and is made a century ago. It has crossed its durability but is of historical importance for the area, that is the reason why it needs utmost importance for its Rehabilitation. The paper deals with the damage that has been occurred in the structure and how to repair and renovate the same keeping in mind that the material deviation could not take place because it shows how in ancient era structures are made of. The building has used lime surkhi mortar along with wood apple as fibrous material for providing adhesiveness in masonry binding. The paper helps in sustainable retrofitting of the structure without changing the integrity of the structure. This helps in maintaining the originality of structure in present era and also help in providing information to the upcoming generation how ancient civil construction has been carried out that withstand even more than a century.

Keywords: Lime Surkhi masonry, rehabilitation, sustainable development, historical building

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Authors: Ming-Tzu Tsai, Jui-Ting Hsu, Chia-Chieh Lin, Feng-Tsai Chiang, Cheng-Chin Huang

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Far infrared (FIR), an invisible and short electromagnetic waves ranges from 6-14 μm also defines as the “growth ray.” Although the mechanism of FIR is still unknown, most data have suggested that FIR could accelerate the skin microcirculation by elevating the blood flow and nitric-oxide (NO) synthesis. In this present work, the effect of FIR irradiation and endothelial cell growth supplement (ECGS) on human umbilical vascular endothelial cells (HUVECs) was evaluated. To understand whether the cell viability and NO production of HUVECs affected by NO, cells with/without ECGS were treated in the presence or absence of L-NAME, an eNOS inhibitor. For FIR exposure, FIR-emitted ceramic powders consisted of a variety of well-mixed metal oxides were developed. The results showed that L-NAME did had a strong effect on the inhibition of NO production, especially in the ECGS-treated group. However, the cell viability of each group was rarely affected in the presence of L-NAME. Cells with the incubation of ECGS showed much higher cell viability compared to the control. Moreover, NO production of HUVECs exposed to FIR irradiation was significantly inhibited in the presence of L-NAME. It suggested that NO could play a role modulating the downstream signals of HUVECs during FIR exposure.

Keywords: far-infrared irradiation (FIR), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), endothelial cell growth supplement (ECGS)

Procedia PDF Downloads 429