Search results for: protein and cell responses

Authors: Muhammad Abdul Latif, Edijanti Goenarwo , Intan Rahmania Eka

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Diarrhea is one of the leading causes of morbidity and mortality in many countries, as well as responsible for the deaths of millions of people each year. Previous research showed that the leaves, bark, and root bark of kedondong contains saponins, tannins, and flavonoids. Tannins have anti-diarrheal effects that work as the freeze of protein / astrigen, and may inhibit the secretion of chloride over the tannate bonding between protein in the intestines. Chemical compounds of flavonoids also have an effect as anti-diarrheal block receptors Cl ˉ in intestinal thus reducing the secretion of Cl ˉ to the intestinal lume. This research aims to know the anti-diarrheal activity of extracts kedondong leaf in mice Balb/C strain males in vivo. This research also proves kedondong leaves as an anti-diarrhea through trial efficacy of kedondong leaves as antisekretori and antimotilitas. This research using post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. If the data obtained homogenous then using ANOVA test. This research using ethanolic extracts kedondong leaf 200, 400 and 800 mg/kg BW to prove there is anti-motility became five treatment groups. The result showed dose of ethanolic extracts kedondong leaf 800 mg/kg BW have significant value (p < 0.005). The conclusion from this extracts kedondong leaf research 800 mg/kg BW have pharmacological effects as antimotility on Balb/C strain male mice.

Keywords: anti-diarrhea, anti-motility, castrol oil, kedondong leaf

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Authors: Nidal H. Abu-Zahra, Aruna P. Wanninayake

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Copper Oxide (CuO) is a p-type semiconductor with a band gap energy of 1.5 eV, this is close to the ideal energy gap of 1.4 eV required for solar cells to allow good solar spectral absorption. The inherent electrical characteristics of CuO nano particles make them attractive candidates for improving the performance of polymer solar cells when incorporated into the active polymer layer. The UV-visible absorption spectra and external quantum efficiency of P3HT/PC70BM solar cells containing different weight percentages of CuO nano particles showed a clear enhancement in the photo absorption of the active layer, this increased the power conversion efficiency of the solar cells by 24% in comparison to the reference cell. The short circuit current of the reference cell was found to be 5.234 mA/cm2 and it seemed to increase to 6.484 mA/cm2 in cells containing 0.6 mg of CuO NPs; in addition the fill factor increased from 61.15% to 68.0%, showing an enhancement of 11.2%. These observations suggest that the optimum concentration of CuO nano particles was 0.6 mg in the active layer. These significant findings can be applied to design high-efficiency polymer solar cells containing inorganic nano particles.

Keywords: copper oxide nanoparticle, UV-visible spectroscopy, polymer solar cells, P3HT/PCBM

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Authors: Seyedeh Mozhgan Seyed Talebi, Chih -Hao Lee

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With an abrupt rise in the power conservation efficiency (PCE) of perovskite solar cells (PSCs) within a short span of time, the toxicity of lead was raised as a major hurdle in the path toward their commercialization. In the present research, a systematic investigation of the electrical and optical characteristics of the all-inorganic CsSnI₃ perovskite absorber layer was performed with the Vienna Ab Initio Simulation Package (VASP) using the projector-augmented wave method. The presence of inorganic halide perovskite offers the advantages of enhancing the degradation resistance of the device, reducing the cost of cells, and minimizing the recombination of generated carriers. The simulated standard device using a 1D simulator like solar cell capacitance simulator (SCAPS) version 3308 involves FTO/n-TiO₂/CsSnI₃ Perovskite absorber/Spiro OmeTAD HTL/Au contact layer. The variation in the device design key parameters such as the thickness and defect density of perovskite absorber, hole transport layer and electron transport layer and interfacial defects are examined with their impact on the photovoltaic characteristic parameters. The effect of an increase in operating temperature from 300 K to 400 K on the performance of CsSnI3-based perovskite devices is also investigated. The optimized standard device at room temperature shows the highest PCE of 25.18 % with FF of 75.71 %, Voc of 0.96 V, and Jsc of 34.67 mA/cm². The outcomes and interpretation of different inorganic Cu-based HTLs presence, such as CuSCN, Cu₂O, CuO, CuI, SrCu₂O₂, and CuSbS₂, here represent a critical avenue for the possibility of fabricating high PCE perovskite devices made of stable, low-cost, efficient, safe, and eco-friendly all-inorganic materials like CsSnI₃ perovskite light absorber.

Keywords: CsSnI₃, hole transporting layer (HTL), lead-free perovskite solar cell, SCAPS-1D software

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Authors: Sudip Mondal, Biswanath Mondal, Sudit S. Mukhopadhyay, Apurba Dey

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Bioactive materials improve devices for a long lifespan but have mechanical limitations. Mechanical characterization is one of the very important characteristics to evaluate the life span and functionality of the scaffold material. After implantation of scaffold material the primary stage rejection of scaffold occurs due to non biocompatible effect of host body system. The second major problems occur due to the effect of mechanical failure. The mechanical and biocompatibility failure of the scaffold materials can be overcome by the prior evaluation of the scaffold materials. In this study chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite (HAp) biomaterial. Thermo-gravimetric and differential thermal analysis (TG-DTA) is carried out to ensure thermal stability. The chemical composition and bond structures of wet ball-milled calcined HAp powder is characterized by Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray (EDX) analysis. Fish scale derived apatite materials consists of nano-sized particles with Ca/P ratio of 1.71. The biocompatibility through cytotoxicity evaluation and MTT assay are carried out in MG63 osteoblast cell lines. In the cell attachment study, the cells are tightly attached with HAp scaffolds developed in the laboratory. The result clearly suggests that HAp material synthesized in this study do not have any cytotoxic effect, as well as it has a natural binding affinity for mammalian cell lines. The synthesized HAp powder further successfully used to develop porous scaffold material with suitable mechanical property of ~0.8GPa compressive stress, ~1.10 GPa a hardness and ~ 30-35% porosity which is acceptable for implantation in trauma region for animal model. The histological analysis also supports the bio-affinity of processed HAp biomaterials in Wistar rat model for investigating the contact reaction and stability at the artificial or natural prosthesis interface for biomedical function. This study suggests the natural sourced fish scale-derived HAp material could be used as a suitable alternative biomaterial for tissue engineering application in near future.

Keywords: biomaterials, hydroxyapatite, scaffold, mechanical property, tissue engineering

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Authors: Elham Vojoudi, Marzieh Mehrafza, Ahmad Hosseini, Azadeh Raofi, Maryam Najafi

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Premature ovarian failure (POF) has become one of the main causes of infertility in women of childbearing age and the incidence of this disorder is increasing year by year. In these patients, poor ovarian response (POR) to gonadotropins reflects a diminished ovarian reserve (DOR) that gives place to few follicles despite aggressive stimulation. Up to now, egg donation is the only way to resolve infertility problems in POF patients. Therefore, some novel aspects such as activating (Akt signaling pathway) and inhibiting (Hippo-signaling) elements have been identified as IVA procedure that promotes primordial follicle activation. In this study, we used the newly developed technique (combination of in vitro activation of dormant follicles (IVA) and stem cell therapy) to promote ovarian follicle growth much more efficiently than the natural, in vivo process for women with POF. Transplantation of Warton Jelly-MSCs to the ovaries of POF patients rescued overall ovarian function. Participants (10 patients) were followed up monthly for a period of six months by hormonal (AMH, FSH, LH and E2), clinical (resuming menstruation), and US (folliculometry) outcomes after a laparoscopic operation. In summary, IVA/WJ-MSC transplantation may provide an effective treatment for POF.

Keywords: POF, in vitro activation, stem cell therapy, infertility

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Authors: Ali A. A. Alqarni, Gamal A. Mohamed, Hossam M. Abdallah, Sabrin R. M. Ibrahim

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Phytochemical investigation of the methanolic extract of aerial parts of Tagetes minuta L. (Family: Asteraceae) using different chromatographic techniques led to the isolation of five compounds; ecliptal (1), scopoletin (2), P-hydroxy benzoic acid (3), patuletin (4), and patuletin-7-O-β-D-glucopyranoside (5) (Figure 1). Their structures were established based on physical, chemical, and spectral data [Ultraviolet (UV), Proton ¹H, Carbon thirteen ¹³C, and Heteronuclear Multiple Bond Correlation (HMBC) NMR], as well as Electrospray Ionization Mass Spectroscopy (ESIMS) and comparison with literature data. Their cytotoxic activity was assessed towards human liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and human colon cancer (HCT116) cancer cell lines using sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards HepG2, MCF7, and HCT116 cells with IC₅₀s ranging from 2.74 to 7.01 μM, compared to doxorubicin (IC₅₀ 0.18, 0.60, and 0.20 μM, respectively), whereas compounds 2, 4, and 5 showed moderate cytotoxic potential with IC50s ranging from 11.71 to 35.64 μM. However, 3 was inactive up to a concentration of 100 μM towards the three tested cancer cell lines.

Keywords: Asteraceae, cytotoxicity, metabolites, Tagetes minuta

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Authors: Mohammed Ahmed Alghamdi, Hazem Mahmoud Ali Darwish, Mostafa Mohamed Abdelraheem

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Transparent conducting oxides (TCOs) possess low resistivity, exhibit good adherence to many substrates, and have good transmission characteristics from the visible to near-infrared wavelengths, which make it useful for various applications. Thin films of transparent conducting oxide (TCO’s) have received much attention because of their wide applications in the field of optoelectronic devices. Advancement of transparent conducting oxides TCO’s may not only lie within the improvement of existing materials in use, but also the development of novel materials. Solar cells are devices, which convert solar energy into electricity, either directly via the photovoltaic effect, or indirectly by first converting the solar energy to heat or chemical energy. Solar power has attracted attention of late as the most advanced of the alternative energy resources. The project aims to access the solar energy in Al-Baha region by search for materials (transparent-conductive oxides (TCO's)) to use in solar cells with highly transparent to the solar spectrum, have low electrical resistivity, be stable under H-plasma, and have a suitable structure in particular for a-Si solar cells. As the PV surface is exposed to the sunlight, the module temperature increases. High ambient temperatures along with long sunlight exposure time increases the temperature impact on PV cells efficiency. Since Al-Baha area is characterized by an atmosphere and pressure different from their counterparts in Saudi Arabia due to the height above sea level, hence it is appropriate to do studies to improve the efficiency of solar cells under these conditions. In this work, some ion change materials will be deposited using either sputtering/ or electron beam evaporation techniques. The optical properties of the synthesized materials will be studied in details for solar cell application. As we will study the effect of some dyes on the optical properties of the prepared films. The efficiency and other parameters of solar cell will be determined.

Keywords: thin films, solar cell, optical properties, electrical properties

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Authors: Y. S. Baraya, B. Umar, A. Aliyu, A. A. Raji, K. A. N. Esievo

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This study was performed to determine the presence of anaemia in randomly selected apparently healthy camels (Camelus dromedarius) brought for slaughter at the Sokoto metropolitan abattoir, Sokoto State, Nigeria. The camels were derived from both sexes, different age groups, functional usages and kept at various localities within and outside Sokoto town. In the study area, studies involving camels were limited in particular the emphasis on the anaemic status of camels brought daily for human consumption. A total of eighty (80) blood samples were collected once a week from these camels within the period of eight (8) weeks to investigate the haematological variations especially packed cell volume (PCV). The PCV analysis revealed anaemia in more than fifty (50) % of the camels studied. However, the actual cause of the anaemia was not investigated but could be caused by infectious agent like protozoan parasite Trypanosoma specie and non-infectious cause such as nutritional deficiency. The PCV examination as a simple, inexpensive and reliable procedure could be part of the routine ante-mortem assessment to evaluate camels for the existence of anaemia since many of the causes of anaemia besides being affecting the meat quality could also be of zoonotic significance.

Keywords: anaemia, camels, packed cell volume, Sokoto abattoir

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Authors: B. Neethu, Diptesh Das

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The present study investigates the performance of a semi-active controller using magneto-rheological dampers (MR) for seismic response reduction of a multi-span bridge. The application of structural control to the structures during earthquake excitation involves numerous challenges such as proper formulation and selection of the control strategy, mathematical modeling of the system, uncertainty in system parameters and noisy measurements. These problems, however, need to be tackled in order to design and develop controllers which will efficiently perform in such complex systems. A control algorithm, which can accommodate un-certainty and imprecision compared to all the other algorithms mentioned so far, due to its inherent robustness and ability to cope with the parameter uncertainties and imprecisions, is the sliding mode algorithm. A sliding mode control algorithm is adopted in the present study due to its inherent stability and distinguished robustness to system parameter variation and external disturbances. In general a semi-active control scheme using an MR damper requires two nested controllers: (i) an overall system controller, which derives the control force required to be applied to the structure and (ii) an MR damper voltage controller which determines the voltage required to be supplied to the damper in order to generate the desired control force. In the present study a sliding mode algorithm is used to determine the desired optimal force. The function of the voltage controller is to command the damper to produce the desired force. The clipped optimal algorithm is used to find the command voltage supplied to the MR damper which is regulated by a semi active control law based on sliding mode algorithm. The main objective of the study is to propose a robust semi active control which can effectively control the responses of the bridge under real earthquake ground motions. Lumped mass model of the bridge is developed and time history analysis is carried out by solving the governing equations of motion in the state space form. The effectiveness of MR dampers is studied by analytical simulations by subjecting the bridge to real earthquake records. In this regard, it may also be noted that the performance of controllers depends, to a great extent, on the characteristics of the input ground motions. Therefore, in order to study the robustness of the controller in the present study, the performance of the controllers have been investigated for fourteen different earthquake ground motion records. The earthquakes are chosen in such a way that all possible characteristic variations can be accommodated. Out of these fourteen earthquakes, seven are near-field and seven are far-field. Also, these earthquakes are divided into different frequency contents, viz, low-frequency, medium-frequency, and high-frequency earthquakes. The responses of the controlled bridge are compared with the responses of the corresponding uncontrolled bridge (i.e., the bridge without any control devices). The results of the numerical study show that the sliding mode based semi-active control strategy can substantially reduce the seismic responses of the bridge showing a stable and robust performance for all the earthquakes.

Keywords: bridge, semi active control, sliding mode control, MR damper

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Authors: Maletsema Alina Mofokeng, Nemera Shargie

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Sorghum is one of the most important cereal crops grown as a source of calories for many people in tropics and sub-tropics of the world. Proper characterisation and evaluation of crop germplasm is an important component for effective management of genetic resources and their utilisation in the improvement of the crop through plant breeding. The objective of the study was to estimate the genetic diversity present in sorghum accessions grown in South Africa using agro-morphological traits and some nutritional contents. The experiment was carried out in Potchefstroom. Data were subjected to correlations, principal components analysis, and hierarchical clustering using GenStat statistical software. There were highly significance differences among the accessions based on agro-morphological and nutritional quality traits. Grain yield was highly positively correlated with panicle weight. Plant height was highly significantly correlated with internode length, leaf length, leaf number, stem diameter, the number of nodes and starch content. The Principal component analysis revealed three most important PCs with a total variation of 78.6%. The protein content ranged from 7.7 to 14.7%, and starch ranged from 58.52 to 80.44%. The accessions that had high protein and starch content were AS16cyc and MP4277. There was vast genetic diversity observed among the accessions assessed that can be used by plant breeders to improve yield and nutritional traits.

Keywords: accessions, genetic diversity, nutritional quality, sorghum

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Authors: Yee-Seul So, Guiseppe Ianiri, Alex Idnurm, Yong-Sun Bahn

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Tor1 is a serine/threonine protein kinase that is widely conserved across eukaryotic species. Tor1 was first identified in Saccharomyces cerevisiae as a target of rapamycin (TOR). The TOR pathway has been implicated in regulating cellular responses to nutrients, proliferation, translation, transcription, autophagy, and ribosome biogenesis. Here we identified two homologues of S. cerevisiae Tor proteins, CNAG_06642 (Tor1) and CNAG_05220 (Tlk1, TOR-like kinase 1), in Cryptococcus neoformans causing a life-threatening fungal meningoencephalitis. Both Tor1 and Tlk1 have rapamycin-binding (RB) domains but Tlk1 has truncated RB form. To study the TOR-signaling pathway in the fungal pathogen, we attempt to construct the tor1Δ and tlk1Δ mutants and phenotypically analyze them. Although we failed to construct the tor1Δ mutant, we successfully construct the tlk1Δ mutant. The tlk1Δ mutant does not exhibit any discernable phenotypes, suggesting that Tlk1 is dispensable in C. neoformans. The essentiality of TOR1 is independently confirmed by constructing the TOR1 promoter replacement strain by using a copper transporter 4 (CTR4) promoter and the TOR1/tor1 heterozygous mutant in diploid C. neoformans strain background followed by sporulation analysis. To further analyze the function of Tor1, we construct TOR1 overexpression mutant using a constitutively active histone H3 in C. neoformans. We find that the Tor1 overexpression mutant is resistant to rapamycin but the tlk1Δ mutant does not exhibit any altered resistance to rapamycin, further confirming that Tor1, but not Tlk1, is critical for TOR signaling. Furthermore, we found that Tor1 is involved in response to diverse stresses, including genotoxic stress, oxidative stress, thermo-stress, antifungal drug treatment, and production of melanin. To identify any TOR-related transcription factors, we screened C. neoformans transcription factor library that we constructed in our previous study and identified several potential downstream factors of Tor1, including Atf1, Crg1 and Bzp3. In conclusion, the current study provides insight into the role of the TOR signaling pathway in human fungal pathogens as well as C. neoformans.

Keywords: fungal pathogen, serine/threonine kinase, target of rapamycin, transcription factor

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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Authors: Gordana Branković, Dejan Dodig, Vesna Pajić, Vesna Kandić, Desimir Knežević, Nenad Đurić

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The wheat grain quality properties are influenced by genotype, environmental conditions and genotype × environment interaction (GEI). The increasing request of more nutritious wheat products will direct future breeding programmes. Therefore, the aim of investigation was to determine: i) variability of the protein content (PC), wet gluten content (WG) and Zeleny sedimentation volume (ZS); ii) components of variance, heritability in a broad sense (hb2), and expected genetic advance as percent of mean (GAM) for PC, WG, and ZS; iii) correlations between PC, WG, ZS, and most important agronomic traits; in order to assess expected breeding success versus environmental impact for these quality traits. The plant material consisted of 30 genotypes of bread wheat (Triticum aestivum L. ssp. aestivum) and durum wheat (Triticum durum Desf.). The trials were sown at the three test locations in Serbia: Rimski Šančevi, Zemun Polje and Padinska Skela during 2010-2011 and 2011-2012. The experiments were set as randomized complete block design with four replications. The plot consisted of five rows of 1 m2 (5 × 0.2 m × 1 m). PC, WG and ZS were determined by the use of Near infrared spectrometry (NIRS) with the Infraneo analyser (Chopin Technologies, France). PC, WG and ZS, in bread wheat, were in the range 13.4-16.4%, 22.8-30.3%, and 39.4-67.1 mL, respectively, and in durum wheat, in the range 15.3-18.1%, 28.9-36.3%, 37.4-48.3 mL, respectively. The dominant component of variance for PC, WG, and ZS, in bread wheat, was genotype with the genetic variance/GEI variance (VG/VG × E) relation of 3.2, 2.9 and 1.0, respectively, and in durum wheat was GEI with the VG/VG × E relation of 0.70, 0.69 and 0.49, respectively. hb2 and GAM values for PC, WG and ZS, in bread wheat, were 94.9% and 12.6%, 93.7% and 18.4%, and 86.2% and 28.1%, respectively, and in durum wheat, 80.7% and 7.6%, 79.7% and 10.2%, and 74% and 11.2%, respectively. The most consistent through six environments, statistically significant correlations, for bread wheat, were between PC and spike length (-0.312 to -0.637); PC, WG, ZS and grain number per spike (-0.320 to -0.620; -0.369 to -0.567; -0.301 to -0.378, respectively); PC and grain thickness (0.338 to 0.566), and for durum wheat, were between PC, WG, ZS and yield (-0.290 to -0.690; -0.433 to -0.753; -0.297 to -0.660, respectively); PC and plant height (-0.314 to -0.521); PC, WG and spike length (-0.298 to -0.597; -0.293 to -0.627, respectively); PC, WG and grain thickness (0.260 to 0.575; 0.269 to 0.498, respectively); PC, WG and grain vitreousness (0.278 to 0.665; 0.357 to 0.690, respectively). Breeding success can be anticipated for ZS in bread wheat due to coupled high values for hb2 and GAM, suggesting existence of additive genetic effects, and also for WG in bread wheat, due to very high hb2 and medium high GAM. The small, and medium, negative correlations between PC, WG, ZS, and yield or yield components, indicate difficulties to select simultaneously for high quality and yield, depending on linkage for particular genetic arrangements to be broken by recombination.

Keywords: bread and durum wheat, genetic advance, protein and wet gluten content, Zeleny sedimentation volume

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Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

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Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: TSPO, molecular modeling, imaging, docking

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Farzad Tofigh, Saeideh Najafi, Reza Heidari, Rashid Jamei

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In order to study the effects of magnetic field on the root system and growth of Phaseolus vulgaris, an experiment was conducted in 2012. The possible involvement of magnetic field (MF) pretreatment in physiological factors of Phaseolus vulgaris was investigated. Seeds were subjected to 10 days with 1.8 mT of magnetic field for 1h per day. MF pretreatment decreased the plant height, fresh and dry weight, length of root and length of shoot, Chlorophyll a, Chlorophyll b and carotenoid in 10 days old seedling. In addition, activity of enzymes such as Catalase and Guaiacol peroxidase was decreased due to MF exposure. Also, the total Protein and DPPH content of the treated by magnetic field was not significantly changed in compare to control groups, while the flavonoid, Phenol and prolin content of the treated of the treated by magnetic field was significantly changed in compare to control groups. Lateral branches of roots and secondary roots increased with MF. The results suggest that pretreatment of this MF plays important roles in changes in crop productivity. In all cases there was observed a slight stimulating effect of the factors examined. The growth dynamics were weakened. The plants were shorter. Moreover, the effect of a magnetic field on the crop of Phaseolus vulgaris and its structure was small.

Keywords: carotenoid, chlorophyll a, chlorophyll b, DPPH, enzymes, flavonoid, germination, growth, phenol, proline, protein, magnetic field

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Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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Authors: Oranso T. Mahlangi, Bhekie B. Mamba

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The occurrence of trace organic compounds (TOrCs) in water has raised health concerns for living organisms. The majority of TorCs, including pharmaceuticals and volatile organic compounds, are poorly monitored, partly due to the high cost of analysis and less strict water quality guidelines in South Africa. Therefore, the removal of TorCs is important to guarantee safe potable water. In this study, ZnO nanoparticles were fabricated in situ in polyethersulfone (PES) polymer solutions. This was followed by membrane synthesis using the phase inversion technique. Techniques such as FTIR, Raman, SEM, AFM, EDS, and contact angle measurements were used to characterize the membranes for several physicochemical properties. The membranes were then evaluated for their efficiency in treating pharmaceutical wastewater and resistance to organic (sodium alginate) and protein (bovine serum albumin) fouling. EDS micrographs revealed uniform distribution of ZnO nanoparticles within the polymer matrix, while SEM images showed uniform fingerlike structures. The addition of ZnO increased membrane roughness as well as hydrophilicity (which in turn improved water fluxes). The membranes poorly rejected monovalent and divalent salts (< 10%), making them resistant to flux decline due to concentration polarization effects. However, the membranes effectively removed carbamazepine, caffeine, sulfamethoxazole, ibuprofen, and naproxen by over 50%. ZnO PES membranes were resistant to organic and protein fouling compared to the neat membrane. ZnO PES ultrafiltration membranes may provide a solution in the reclamation of wastewater.

Keywords: trace organic compounds, pharmaceuticals, membrane fouling, wastewater reclamation

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Authors: Cristina Isabrl de Oliveira SAntos

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The study aims to investigate how transferrable and effective career conversations could be, in the context of general track Portuguese secondary schools, with the view of improving students’ career competencies. It does so by analysing: 1) the extent to which students’ perceptions of career conversations relate with their existing career competencies, 2) the extent to which each of the parameters; perceptions of career conversations and student career competencies, relate with student situational and personal characteristics, 3) how patterns in perceptions of headteachers and of teachers at a school, regarding the implementation of career conversations, correlate to the views of students regarding career conversations and to school contextual characteristics. Data were collected from 27 secondary schools out of 32 in the same district of Aveiro, in Portugal. Interviews were performed individually, with 27 headteachers, and in groups, with a total of 10 teacher groups and 11 student groups. Survey responses were also collected from742 studentsand 310 teachers. Interview responses were coded and analysed using grounded theory principles. Data from questionnaires is currently beingscrutinised through descriptive statistics with SPSS, and Structural Equation Modelling (SEM). Triangulation during different stages of data analysis uses the principles of retroduction and abduction of the realist evaluation framework. Conclusions from the pilot-study indicate that student perceptions scores on content and relationship in career conversations change according to their career competencies and the type of school. Statistically significant differences in perceptions of career conversations were found for subgroups based on gender and parent educational level.

Keywords: career conversations, career competencies, secondary education, teachers

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Authors: B. Nageshwar Rao

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Urinary tract infection (UTI) represents the most commonly acquired bacterial infection worldwide, with substantial morbidity, mortality, and economic burden. The objective of the study is to characterize the microbial profiles of uropathogenic in the obstetric population by RTPCR. Study design: An observational cross-sectional study was performed at a single tertiary health care hospital among 50 pregnant women with UTIs, including asymptomatic and symptomatic patients attending the outpatient department and inpatient department of Obstetrics and Gynaecology.Methods: Serotyping and genes detection of various uropathogens were studied using RTPCR. Pulse filed gel electrophoresis methods were used to determine the various genetic profiles. Results: The present study shows that CsgD protein, involved in biofilm formation in Escherichia coli, VIM1, IMP1 genes for Klebsiella were identified by using the RTPCR method. Our results showed that the prevalence of VIM1 and IMP1 genes and CsgD protein in E.coli showed a significant relationship between strong biofilm formation, and this may be due to the prevalence of specific genes. Finally, the genetic identification of RTPCR results for both bacteria was correlated with each other and concluded that the above uropathogens were common isolates in producing Biofilm in the pregnant woman suffering from urinary tract infection in our hospital observational study.

Keywords: biofilms, Klebsiella, E.coli, urinary tract infection

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Authors: Diego Caballero Vélez

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In 1997 the Schengen Convention was incorporated in the mainstream of EU law by the Amsterdam Treaty. It came into effect in 1999 with the abolition of internal border controls in the EU, a milestone in the European integration project. In the meantime, due to the Yugoslav wars, nearly 700,000 asylum applications were filed in the European countries provoking a major refugee crisis. During this period, the opening of Eastern Europe fostered more cooperation and policy-making at the EU level in migration issues. Currently, a similar migratory crisis is taking place in Europe. The Syrian war has caused the most massive influx of immigrants in Europe since World War II. Nevertheless, the EU is adopting different migration policies from those implemented during the Yugoslav migration crisis. The current crisis has not led to a common European position but national responses have been offered on migration policies and responsibility for border security and asylum-seekers. A lot of factors can explain this change from a cooperation scenario to a no cooperation one, such as the economic crisis, but this research is focused on the premise that 'threat perception' lies at the core of some states grand strategies towards migration and it also influences in multilateral or unilateral responses. Migration rests at the nexus of three dimensions of security, including geopolitical interests, material production, and internal security. According to some scholars, migration policy is an 'integral instrument' of state grand strategy in that context. Political integration at the EU might be altered with the emergence of existential threats. In other words, some areas of the European cooperation can be transformed when a 'critical juncture' occurs, for instance a migration crisis. In that instance, Member states could see migration as a matter of threat that modifies their national interests and willingness to embrace international cooperation. This research will focus on EU Member states´ perceptions of the 90´s migration crisis and the current one. The goal is to evaluate to what extent the perceptions of threat are one of the main factors for explaining the transition from a cooperation scenario to a no-cooperation one in European asylum and security policies. To analyze threat perception in both migration crisis, some relevant Member states are treated as cases of study and a comparative analysis is carried out based on public opinion polls, public and policy discourse in migration, voting practices and deconstruction of the migration policies themselves both at EU level and a national one.

Keywords: cooperation, migration crisis, national responses, threat perception

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Authors: Ting Wang, Pierre Marle, Vera I. Slaveykova, Kristin Schirmer, Wei Liu

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Metal-based nanoparticles (NPs) are considered detrimental to aquatic organisms due to their potential accumulation. However, little is known about the mechanisms underlying these effects and their species-specificity. Here, we used stable silver (Ag) NPs (20 nm, from 10 to 500 μg/L) with a low dissolution rate (≤2.4%) to study the bioaccumulation and biological impacts in two freshwater gastropods: Lymnaea stagnalis and Planorbarius corneus. No mortality was detected during the experiments. Ag bioaccumulation showed a dose-related increase with an enhanced concentration in both species after 7d exposure. L. stagnalis displayed a higher accumulation for AgNPs than P. corneus (e.g., up to 18- and 15-fold in hepatopancreas and hemolymph, respectively), which could be due to the more active L. stagnalis having greater contact with suspended AgNPs. Furthermore, the hepatopancreas and stomach were preferred organs for bioaccumulation compared to the kidney, mantle and foot. Regarding biological responses, the hemolymph rather than hepatopancreas appeared more susceptible to oxidative stress elicited by AgNPs, as shown by significantly increasing lipid peroxidation (i.e., formation of malondialdehyde). Neurotoxicity was detected in L. stagnalis when exposed to high concentrations (500 μg/L). Comparison with impacts elicited by dissolved Ag revealed that the effects observed on AgNPs exposure were mainly attributable to NPs. These results highlighted the relationship between the physiological traits, bioaccumulation, and toxicity responses of these two species to AgNPs and demonstrated the necessity of species-specificity considerations when assessing the toxicity of NPs.

Keywords: nanotoxicity, freshwater gastropods, species-specificity, metals, physiological traits

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Authors: Du T. Tran, Quyen T. L. Hoang

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The role of language learning strategies in second language acquisition has received increased attention across several disciplines in recent years. Language learning strategies have been shown to occur in many studies over the passing years with the aim of improving the efficiency of language learning. Following previous studies, this study endeavors to scrutinize language learning strategies employed by the students at Vo Minh Duc high school and the effect of motivation on students’ learning strategy choices. The responses are examined quantitatively and qualitatively to enhance their validity and reliability. Data are collected from 342 students’ responses to the questionnaire, interviews with ten teachers and fifteen students, and classroom observations. The findings reveal that students’ motivation has an enormous impact on the choice of language learning strategies. The results simultaneously show that students use many language learning strategies to enhance their communicative competence, but the most frequently used ones are cognitive and affective ones. Significant correlations among types of learning strategies and the influence of motivation on the choices of language learning strategies were consistent with previous studies. The study’s results are expected to be beneficial to teachers of English and students in terms of narrowing the gap between the students' language learning strategies and their teaching methodologies preferences and sketching out the best strategies to enhance students’ speaking skills. The implications of these findings and the importance of viewing learners holistically are discussed, and recommendations are made for ongoing research.

Keywords: learning strategies, speaking skills, memorization strategies, cognitive strategies, affective strategies

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Authors: Zine Kechrid, Samira Bouhalit

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Aim: We studied the effect of intraperitonial zinc treatment on nickel sulphate-induced hepatotoxicity and nephrotoxicity in Wistar strain male albino rats. Materials and Methods: Liver and kidney dysfunction parameters represented by aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), blood glucose, serum total protein, serum urea, serum creatinine, and serum belurebin were estimated. Liver glutathione level, catalase and GPx activities were also determined in liver as indicators of oxidative damage. Result: Nickel treatment led to high serum glucose concentration and produced hepatotoxicity and nephrotoxicity characterized by increasing GPT, GOT and alkaline phosphatase activities, serum total protein, serum urea, serum creatinine and serum belurebin concentrations. In addition, liver glutathione level, catalase and GSH-Px activities diminished due to high lipid peroxidation. The simultaneous administration of zinc with nickel sulphate resulted in a remarkable improvement of the previous parameters compared with rats treated with nickel alone. Conclusion: In conclusion, nickel sulphate led to liver and kidney dysfunctions and hepatic lipid peroxidation in animals, but simultaneous treatment with zinc offers a relative protection against nickel induced hepatotoxicity, nephrotoxicity and lipid peroxidation.

Keywords: nickel, zinc, rats, GOT, GPT, nephrotoxicity, hepatotoxicity

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Authors: Le Xuan Cau

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Flash flood is occurred in short time rainfall interval: from 1 hour to 12 hours in small and medium basins. Flash floods typically have two characteristics: large water flow and big flow velocity. Flash flood is occurred at hill valley site (strip of lowland of terrain) in a catchment with large enough distribution area, steep basin slope, and heavy rainfall. The risk of flash floods is determined through Gridded Basin Flash Flood Potential Index (GBFFPI). Flash Flood Potential Index (FFPI) is determined through terrain slope flash flood index, soil erosion flash flood index, land cover flash floods index, land use flash flood index, rainfall flash flood index. Determining GBFFPI, each cell in a map can be considered as outlet of a water accumulation basin. GBFFPI of the cell is determined as basin average value of FFPI of the corresponding water accumulation basin. Based on GIS, a tool is developed to compute GBFFPI using ArcObjects SDK for .NET. The maps of GBFFPI are built in two types: GBFFPI including rainfall flash flood index (real time flash flood warning) or GBFFPI excluding rainfall flash flood index. GBFFPI Tool can be used to determine a high flash flood potential site in a large region as quick as possible. The GBFFPI is improved from conventional FFPI. The advantage of GBFFPI is that GBFFPI is taking into account the basin response (interaction of cells) and determines more true flash flood site (strip of lowland of terrain) while conventional FFPI is taking into account single cell and does not consider the interaction between cells. The GBFFPI Map of QuangNam, QuangNgai, DaNang, Hue is built and exported to Google Earth. The obtained map proves scientific basis of GBFFPI.

Keywords: ArcObjects SDK for NET, basin average value of FFPI, gridded basin flash flood potential index, GBFFPI map

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Authors: Ehab El-Dabaa, Omnia Ali, Mohamed Abd El-Hady, Ahmed Osman

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Recombinant human interferon alpha 2 (rhIFN-α2) is FDA approved for treatment of some viral and malignant diseases. Approved pegylated rhIFN-α2 drugs have highly improved pharmacokinetics, pharmacodynamics and therapeutic efficiency compared to native protein. In this work, we studied the pegylation of purified properly refolded rhIFN-α2b using linear 20kDa PEG-NHS (polyethylene glycol- N-hydroxysuccinimidyl ester) to prepare pegylated rhIFN-α2b with high stability and activity. The effect of different parameters like rhIFN-α2b final concentration, pH, rhIFN-α2b/PEG molar ratios and reaction time on the efficiency of pegylation (high percentage of monopegylated rhIFN-α2b) have been studied in small scale (100µl) pegylation reaction trials. Study of the percentages of different components of these reactions (mono, di, polypegylated rhIFN-α2b and unpegylated rhIFN-α2b) indicated that 2h is optimum time to complete the reaction. The pegylation efficiency increased at pH 8 (57.9%) by reducing the protein concentration to 1mg/ml and reducing the rhIFN-α2b/PEG ratio to 1:2. Using larger scale pegylation reaction (65% pegylation efficiency), ion exchange chromatography method has been optimized to prepare and purify the monopegylated rhIFN-α2b with high purity (96%). The prepared monopegylated rhIFN-α2b had apparent Mwt of approximately 65 kDa and high in vitro antiviral activity (2.1x10⁷ ± 0.8 x10⁷ IU/mg). Although it retained approximately 8.4 % of the antiviral activity of the unpegylated rhIFN-α2b, its activity is high compared to other pegylated rhIFN-α2 developed by using similar approach or higher molecular weight branched PEG.

Keywords: antiviral activity, rhIFN-α2b, pegylation, pegylation efficiency

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Authors: Tanima Chatterjee, Maitree Bhattacharyya

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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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Authors: Balakrishna Shetty

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Introduction: Stem Cell Imaging is a challenging field since the advent of Stem Cell treatment in humans. Series of research on tagging and tracking the stem cells has not been very effective. The present study is an effort by the authors to track the stem cells injected into calf muscles by Magnetic Resonance Diffusion Weighted Imaging. Materials and methods: Stem Cell injection deep into the calf muscles of patients with peripheral vascular disease is one of the recent treatment modalities followed in our institution. 5 patients who underwent deep intramuscular injection of stem cells as treatment were included for this study. Pre and two hours Post injection MRI of bilateral calf regions was done using 1.5 T Philips Achieva, 16 channel system using 16 channel torso coils. Axial STIR, Axial Diffusion weighted images with b=0 and b=1000 values with back ground suppression (DWIBS sequence of Philips MR Imaging Systems) were obtained at 5 mm interval covering the entire calf. The invert images were obtained for better visualization. 120ml of autologous bone marrow derived stem cells were processed and enriched under c-GMP conditions and reduced to 40ml solution containing mixture of above stem cells. Approximately 40 to 50 injections, each containing 0.75ml of processed stem cells, was injected with marked grids over the calf region. Around 40 injections, each of 1ml normal saline, is injected into contralateral leg as control. Results: Significant Diffusion hyper intensity is noted at the site of injected stem cells. No hyper intensity noted before the injection and also in the control side where saline was injected conclusion: This is one of the earliest studies in literature showing diffusion hyper intensity in intramuscularly injected stem cells. The advantages and deficiencies in this study will be discussed during the presentation.

Keywords: stem cells, imaging, DWI, peripheral vascular disease

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Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: Wafa Al Jabri

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Sickle cell disease (SCD) is a genetic blood disorder that is characterized by a severe painful crisis. SCD among children requires long term dependencies and high caregiving demands that increase the overall family burdens. It is, therefore, essential to examine, support, and promote the well-being of families of children with SCD. Although there has been considerable progress in the international research on family quality of life (FQOL) in recent years; however, research in this field is relatively recent and diverse. Oman is a country in which family quality of life has definitely been under-researched. Therefore, the purpose of the study is to describe the FQOL in families of children with SCD in Oman. The study will also examine the relationships between child, mother, and family-related factors that may influence the overall FQOL. Theoretical Framework: The study is guided by the unified theory of family quality of life to help in understanding the concept of FQOL and the factors that shape it. Method:A convenience sample of 98 mothers of children with SCD will be recruited from the pediatric hematology clinic at Sultan Qaboos University Hospital in Oman to participate in this descriptive, cross sectional, correlational study. Data will be obtained using a self-administered questionnaire that includes child and mother socio-demographic data, questions about the number of visits and admissions to health care facilities for vaso- occlusive crises (VOCs), the Perceived Stress Scale-10, and the Beachcenter-FQOL scale. Anticipated Results: It is expected to find an association among frequency of VOCs, mother’s perceived stress level, and FQOL in families of children with SCD in Oman. Family type, socio-economic status, and number of SCD children in the family are also expected to influence the overall FQOL. Conclusion: The findings of the study might be pivotal in designing and implementing tailored family-based interventions to improve families’ wellbeing.

Keywords: family quality of life, sickle cell disaes, children, family well-being

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