Search results for: red blood cells

Authors: Isaac Makundi, Kazuo Nishigaki

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The Tsushima leopard cat (TLC) Prionailurus bengalensis euptilurus, designated a National Natural Monument of Japan, inhabits Tsushima Island, Nagasaki Prefecture, Japan. TLC is considered a subspecies of P. bengalensis, and lives only on Tsushima Island. TLCs are threatened by various infectious diseases. Feline leukemia virus (FeLV) causes a serious infectious disease with a poor prognosis in cats. Therefore, the transmission of FeLV from Tsushima domestic cats (TDCs) to TLCs may threaten the TLC population. We investigated the FeLV infection status of both TDCs and TLCs on Tsushima Island by screening blood samples for FeLV p27 antigen and using PCR to amplify the full-length FeLV env gene. The prevalence of FeLV was 6.4% in TDCs and 0% in TLCs. We also demonstrated that the virus can replicate in the cells of TLCs, suggesting its potential cross-species transmission. The viruses in TDCs were classified as genotype I/clade 3, which is prevalent on a nearby island, based on previous studies of FeLV genotypes and FeLV epidemiology. The FeLV viruses identified on Tsushima Island can be further divided into two lineages within genotype I/clade 3, which are geographically separated in Kamijima and Shimojima, indicating that FeLV may have been transmitted to Tsushima Island at least twice. Monitoring FeLV infection in the TDC and TLC populations is highly recommended as part of the TLC surveillance and management strategy.

Keywords: epidemiology, Feline leukemia virus, Tsushima Island, wildlife management

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Authors: Jamilah Syafawati Yaacob, Muhammad Aiman Ramli

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Cili padi or Capsicum frutescens is one of capsicum species from nightshade family, Solanaceae. It is famous in Malaysia and is widely used as a food ingredient. Capsicum frutescens also possess vast medicinal properties. The objectives of this study are to determine the most optimum 2,4-D hormone concentration for callus induction from stem explants C. frutescens and the effects of different 2,4-D concentrations on expression of compounds from C. frutescens. Seeds were cultured on MS media without hormones (MS basal media) to yield aseptic seedlings of this species, which were then used to supply explant source for subsequent tissue culture experiments. Stem explants were excised from aseptic seedlings and cultured on MS media supplemented with various concentrations (0.1, 0.3 and 0.5 mg/L) of 2,4-D to induce formation of callus. Fresh weight, dry weight and callus growth percentage in all samples were recorded. The highest mean of dry weight was observed in MS media supplemented with 0.5 mg/L 2,4-D, where 0.4499 ± 0.106 g of callus was produced. The highest percentage of callus growth (16.4%) was also observed in cultures supplemented with 0.5 mg/L 2,4-D. The callus samples were also subjected to HPLC-MS to evaluate the effect of hormone concentration on expression of bio active compounds in different samples. Results showed that caffeoylferuloylquinic acids were present in all samples, but was most abundant in callus cells supplemented with 0.3 & 0.5 mg/L 2,4-D. Interestingly, there was an unknown compound observed to be highly expressed in callus cells supplemented with 0.1 mg/L 2,4-D, but its presence was less significant in callus cells supplemented with 0.3 and 0.5 mg/L 2,4-D. Furthermore, there was also a compound identified as octadecadienoic acid, which was uniquely expressed in callus supplemented with 0.5 mg/L 2,4-D, but absent in callus cells supplemented with 0.1 and 0.3 mg/L 2,4-D. The results obtained in this study indicated that plant growth regulators played a role in expression of secondary metabolites in plants. The increase or decrease of these growth regulators may have triggered a change in the secondary metabolite biosynthesis pathways, thus causing differential expression of compounds in this plant.

Keywords: callus, in vitro, secondary metabolite, 2, 4-Dichlorophenoxyacetic acid

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Authors: S. S. Salehi, A. Shamloo

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Poor ability of cartilage tissue when experiencing a damage leads scientists to use tissue engineering as a reliable and effective method for regenerating or replacing damaged tissues. An artificial tissue should have some features such as biocompatibility, biodegradation and, enough mechanical properties like the original tissue. In this work, a composite hydrogel is prepared by using natural and synthetic materials that has high porosity. Mechanical properties of different combinations of polymers such as modulus of elasticity were tested, and a hydrogel with good mechanical properties was selected. Bone marrow derived mesenchymal stem cells were also seeded into the pores of the sponge, and the results showed the adhesion and proliferation of cells within the hydrogel after one month. In comparison with previous works, this study offers a new and efficient procedure for the fabrication of cartilage like tissue and further cartilage repair.

Keywords: cartilage tissue engineering, hydrogel, mechanical strength, mesenchymal stem cell

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Authors: Saimir Heta, Ilma Robo, Nevila Alliu, Tea Meta

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Background: Plasma levels of inflammatory markers are the expression of the infectious wastes of existing periodontitis, as well as of existing inflammation everywhere in the body. Materials and Methods: The study consists of the clinical part of the measurement of inflammatory markers of 23 patients diagnosed with chronic periodontitis and the recording of parental periodontal parameters of patient periodontal status: hemorrhage index and probe values, before and 7-10 days after non-surgical periodontal treatment. Results: The level of fibrinogen drops according to the categorization of disease progression, active and passive, with the biggest % (18%-30%) at the fluctuation 10-20 mg/d. Fluctuations in fibrinogen level according to the age of patients in the range 0-10 mg/dL under 40 years and over 40 years was 13%-26%, in the range 10-20 mg/dL was 26%-22%, in the 20-40 mg/dL was 9%-4%. Conclusions: Non-surgical periodontal treatment significantly reduces the level of non-inflammatory markers in the blood. Oral health significantly reduces the potential source for periodontal bacteria, with the potential of promoting thromboembolism, through interaction between thrombocytes.

Keywords: chronic periodontitis, atherosclerosis, risk factor, inflammatory markers

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Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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Authors: Muhsin Kizhisseri, Jorg Schluter, Saleh Gharie

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Atherosclerosis is the main reason of stroke, which is one of the deadliest diseases in the world. The carotid artery in the brain is the prominent location for atherosclerotic progression, which hinders the blood flow into the brain. The inclusion of computational fluid dynamics (CFD) into the diagnosis cycle to understand the hemodynamics of the patient-specific carotid artery can give insights into stroke prediction. Realistic outlet boundary conditions are an inevitable part of the numerical simulations, which is one of the major factors in determining the accuracy of the CFD results. The Windkessel model-based outlet boundary conditions can give more realistic characteristics of the distal vascular branches of the carotid artery, such as the resistance to the blood flow and compliance of the distal arterial walls. This study aims to find the most influential distal branches of the carotid artery by using the Windkessel model parameters in the outlet boundary conditions. The parametric study approach to Windkessel model parameters can include the geometrical features of the distal branches, such as radius and length. The incorporation of the variations of the geometrical features of the major distal branches such as the middle cerebral artery, anterior cerebral artery, and ophthalmic artery through the Windkessel model can aid in identifying the most influential distal branch in the carotid artery. The results from this study can help physicians and stroke neurologists to have a more detailed and accurate judgment of the patient's condition.

Keywords: stroke, carotid artery, computational fluid dynamics, patient-specific, Windkessel model, distal vascular branches

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Authors: Ehsan Yazdanpanah Moghadam, Muthukumaran Packirisamy

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In the present study, a design of the suspended polymeric microfluidic platform is introduced that is fabricated with three polymeric layers. Changing the microchannel plane to be perpendicular to microcantilever plane, drastically decreases moment of inertia in that direction. In addition, the platform is made of polymer (around five orders of magnitude less compared to silicon). It causes significant increase in the sensitivity of the cantilever deflection. Next, although the dimensions of this platform are constant, by misaligning the embedded microchannels laterally in the suspended microfluidic platform, the sensitivity can be highly increased. The investigation is studied on four fluids including water, seawater, milk, and blood for flow ranges from low rate of 5 to 70 µl/min to obtain the best design with the highest sensitivity. The best design in this study shows the sensitivity increases around 50% for water, seawater, milk, and blood at the flow rate of 70 µl/min by just misaligning the embedded microchannels in the suspended polymeric microfluidic platform.

Keywords: microfluidic, MEMS, biosensor, microresonator

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Authors: Joanne Rieta Miranda

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Learning anatomy and physiology among Deaf Non-Science major students is a challenge. They have this mindset that Anatomy and Physiology are difficult and very technical. In this study, nine (9) deaf students who are business majors were considered. Non-conventional teaching strategies and classroom activities were employed such as cooperative learning, virtual lab, Facebook live, big sky, blood typing, mind mapping, reflections, etc. Of all the activities; the deaf students ranked cooperative learning as the best learning activity. This is where they played doctors. They measured the pulse rate, heart rate and blood pressure of their partner classmate. In terms of mindset, 2 out of 9 students have a growth mindset with some fixed ideas while 7 have a fixed mindset with some growth ideas. All the students passed the course. Three out of nine students got a grade of 90% and above. The teacher was evaluated by the deaf students as very satisfactory with a mean score of 3.54. This means that the learner-centered practices in the classroom are manifested to a great extent.

Keywords: deaf students, learning anatomy and physiology, teaching strategies, learner-entered practices

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Authors: Zohra Benfodda, Valentin Duvauchelle, Chaimae Majdi, David Bénimélis, Catherine Dunyach-Remy, Patrick Meffre

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New antibiotics are necessary to treat microbial pathogens, especially ESKAPE pathogens that are becoming increasingly resistant to available treatment. Despite the medical need, the number of newly approved drugs continues to decline. The majority of antibiotics under clinical development are natural products or derivatives thereof. 43 juglone/naphthazarin derivatives were synthesized using Minisci-type direct C–H alkylation and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA. Different compounds of the synthesized series showed promising activity against clinical and reference MSSA (MIC: 1–8 μg/ml) and good efficacy against clinical MRSA (MIC: 2–8 μg/ml) strains. The synergistic effects of active compounds were evaluated with reference antibiotics (vancomycin and cloxacillin), and it was found that the antibiotic combination with those active compounds efficiently enhanced the antimicrobial activity and consequently the MIC values of reference antibiotics were lowered up to 1/16th of the original MIC. These synthesized compounds did not present hemolytic activity on sheep red blood cells. In addition to the in silico prediction of ADME profile parameter which is promising and encouraging for further development.

Keywords: juglone, naphthazarin, antibacterial, clinical MRSA, synergistic studies, MIC determination

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Authors: Shackira Am, Jos T. Puthur

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The phytostabilization potential of a halophyte Acanthus ilicifolius L. has been evaluated with special attention to the nutritional as well as anatomical adaptations developed by the plant. Distribution of essential elements influenced by the excess Zn²⁺ ions in the root tissue was studied by FEG-SEM EDX microanalysis. Significant variations were observed in the uptake and allocation of mineral elements like Mg, P, K, S, Na, Si and Al in the root of A. ilicifolius. The increase in S is in correlation with the increased synthesis of glutathione which might be involved in the biosynthesis of phytochelatins. This in turn might be aiding the plant to tolerate the adverse environmental conditions by stabilizing the excess Zn in the root tissue itself. Moreover it is revealed that most of the Zn were accumulated towards the central region near the vascular tissue. Treatment with ZnSO₄ in A. ilicifolius caused significant increase in the number of glandular trichomes on the adaxial leaf surface as compared to the leaves of control plants. In addition to this, A. ilicifolius when treated with ZnSO₄, exhibited a deeply stained layer of cells immediate to the endodermis, forming more or less a ring like structure around the xylem vessels. Phloem cells in these plants were crushed/reduced in numbers. There were no such deeply stained cells forming a ring around the xylem vessels in the control plants. These adaptive responses make the plant a suitable candidate for the phytostabilization of Zn. In addition the nutritional adjustment of the plant equips them for a better survival under increased concentration of Zn²⁺.

Keywords: Acanthus ilicifolius, mineral elements, phytostabilization, zinc

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Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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Authors: M. Borgie, Z. Dagher, F. Ledoux, A. Verdin, F. Cazier, H. Greige, P. Shirali, D. Courcot

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In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution and fine particulate matter (PM2.5) as carcinogenic to humans. Despite the clearly relationship established by epidemiological studies between PM exposure and the onset of respiratory and cardiovascular diseases, uncertainties remain about the physiopathological mechanisms responsible for these diseases. The aim of this work was to evaluate the toxicological effects of two samples of atmospheric PM2.5 collected at urban and rural sites on human bronchial epithelial cells, BEAS-2B, especially to investigate the metabolic activation of organic compounds, the alteration of epigenetic mechanisms (i.e. microRNAs genes expression), the phosphorylation of H2AX and the telomerase activity. Our results showed a significant increase in CYP1A1, CYP1B1, and AhRR genes expression, miR-21 gene expression, H2AX phosphorylation and telomerase activity in BEAS-2B cells after their exposure to PM2.5, both in a dose and site-dependent manner. These results showed that PM2.5, especially urban PM, are able to induce the expression of metabolizing enzymes which can provide metabolic biotransformation of organic compounds into more toxic and carcinogenic metabolites, and to induce the expression of the oncomiR miR-21 which promotes cell growth and enhances tumor invasion and metastasis in lung cancer. In addition, our results have highlighted the role of PM2.5 in the activation of telomerase, which can maintain the telomeres length and subsequently preventing cell death, and have also demonstrated the ability of PM2.5 to induce DNA breaks and thus to increase the risk of mutations or chromosomal translocations that lead to genomic instability. All these factors may contribute to cell abnormalities, and thus the development of cancer.

Keywords: BEAS-2B cells, carcinogenesis, epigenetic alterations and genotoxicity, PM2.5

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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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: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Malgorzata J. Rybak-Smith, Benedicte Thiebaut, Simon Johnson, Peter Bishop, Helen E. Townley

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Gadolinium doped titania (TiO2:Gd) nanoparticles (NPs) can be activated by X-ray radiation to generate Reactive Oxygen Species (ROS), which can be effective in killing cancer cells. As such, treatment with these NPs can be used to enhance the efficacy of conventional radiotherapy. Incorporation of the NPs in to tumour tissue will permit the extension of radiotherapy to currently untreatable tumours deep within the body, and also reduce damage to neighbouring healthy cells. In an attempt to find a fast and scalable method for the synthesis of the TiO2:Gd NPs, the use of Flame Spray Pyrolysis (FSP) was investigated. A series of TiO2 NPs were generated with 1, 2, 5 and 7 mol% gadolinium dopant. Post-synthesis, the TiO2:Gd NPs were silica-coated to improve their biocompatibility. Physico-chemical characterisation was used to determine the size and stability in aqueous suspensions of the NPs. All analysed TiO2:Gd NPs were shown to have relatively high photocatalytic activity. Furthermore, the FSP synthesized silica-coated TiO2:Gd NPs generated enhanced ROS in chemico. Studies on rhabdomyosarcoma (RMS) cell lines (RD & RH30) demonstrated that in the absence of irradiation all TiO2:Gd NPs were inert. However, application of TiO2:Gd NPs to RMS cells, followed by irradiation, showed a significant decrease in cell proliferation. Consequently, our studies showed that the X-ray-activatable TiO2:Gd NPs can be prepared by a high-throughput scalable technique to provide a novel and affordable anticancer therapy.

Keywords: cancer, gadolinium, ROS, titania nanoparticles, X-ray

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Authors: Viviane A. O. Silva, Angela M. Costa, Glaucia N. M. Hajj, Ana Preto, Aline Tansini, Martin Roffé, Peter Jordan, Rui M. Reis

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Autophagy is a recycling and degradative system suggested to be a major cell death pathway in cancer cells. Autophagy pathway is interconnected with the endocytosis pathways sharing the same ultimate lysosomal destination. Lysosomes are crucial regulators of cell homeostasis, responsible to downregulate receptor signalling and turnover. It seems highly likely that derailed endocytosis can make major contributions to several hallmarks of cancer. WNK2, a member of the WNK (with-no-lysine [K]) subfamily of protein kinases, had been found downregulated by its promoter hypermethylation, and has been proposed to act as a specific tumour-suppressor gene in brain tumors. Although some contradictory studies indicated WNK2 as an autophagy modulator, its role in cancer cell death is largely unknown. There is also growing evidence for additional roles of WNK kinases in vesicular traffic. Aim: To evaluate the role of WNK2 in autophagy and endocytosis on glioma context. Methods: Wild-type (wt) A172 cells (WNK2 promoter-methylated), and A172 transfected either with an empty vector (Ev) or with a WNK2 expression vector, were used to assess the cellular basal capacities to promote autophagy, through western blot and flow-cytometry analysis. Additionally, we evaluated the effect of WNK2 on general endocytosis trafficking routes by immunofluorescence. Results: The re-expression of ectopic WNK2 did not interfere with autophagy-related protein light chain 3 (LC3-II) expression levels as well as did not promote mTOR signaling pathway alteration when compared with Ev or wt A172 cells. However, the restoration of WNK2 resulted in a marked increase (8 to 92,4%) of Acidic Vesicular Organelles formation (AVOs). Moreover, our results also suggest that WNK2 cells promotes delay in uptake and internalization rate of cholera toxin B and transferrin ligands. Conclusions: The restoration of WNK2 interferes in vesicular traffic during endocytosis pathway and increase AVOs formation. This results also suggest the role of WNK2 in growth factor receptor turnover related to cell growth and homeostasis and associates one more time, WNK2 silencing contribution in genesis of gliomas.

Keywords: autophagy, endocytosis, glioma, WNK2

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Authors: Jihoon Yang, Jeong II Choi

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Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

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Authors: Jesus Alfredo Ortega Granados, Pandiyan Thangarasu

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Antibiotic tetracycline presents as a micro-contaminant in fresh water, wastewater and soils, causing environmental and health problems. In this work, tetracycline (TC) has been employed as chemo-sensor for the recognition of Al³⁺ without interring other ions, and the results show that it enhances the fluorescence intensity for Al³⁺ and there is no interference from other coexisting cation ions (Cd²⁺, Ni²⁺, Co²⁺, Sr²⁺, Mg²⁺, Fe³⁺, K⁺, Sm³⁺, Ag⁺, Na⁺, Ba²⁺, Zn²⁺, and Mn²⁺). For the addition of Cu²⁺ to [TET-Al³⁺], it appears that the intensity of fluorescence has been quenched. Other combinations of metal ions in addition to TC do not change the fluorescence behavior. The stoichiometry determined by Job´s plot for the interaction of TC with Al³⁺ was found to be 1:1. Importantly, the detection of Al³⁺⁺ successfully employed in the real samples like living cells, and it was found that TC efficiently performs as a fluorescent probe for Al³⁺ ion in living systems, especially in Saccharomyces cerevisiae; this is confirmed by confocal laser scanning microscopy.

Keywords: chemo-sensor, recognition of Al³⁺ ion, Saccharomyces cerevisiae, tetracycline,

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Authors: Chahrazed Bendenia, Souhila Bendenia, Samia Moulebhar, Hanaa Merad-Dib, Sarra Merabet, Sid Ahmed Khantar, Baghdad Hadri

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In recent years, organic solar cells (OSCs) have become the fundamental concern of researchers thanks to their advantages in terms of flexibility, manufacturing processes and low cost. The performance of these devices is influenced by various factors, such as the layers introduced in the stacking of the solar cell realized. In our work, the modeling of a reverse OSC under AM1.5G illumination will be determined. The photo-active polymer/fullerene layer will be analyzed from the polymer variation of this layer using the SCAPS simulator to extract the J-V characteristics: open circuit voltage (Voc), short circuit current (Jsc), filling factor (FF) and power conversion efficiency (η). The results obtained indicated that the materials used have a significant impact on improving the photovoltaic parameters of the devices studied.

Keywords: solar, polymer, simulator, characteristics

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Authors: Afzaal Bashir, Sunaina Afzaal

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Background: Facial contour deformities associated with pigmentary changes are of major concern for plastic surgeons, both being important and difficult in treating such issues. No definite ideal treatment option is available to simultaneously address both the contour defect as well as related pigmentation. Objectives: The aim of the current study is to compare the long-term effects of conventional adipose tissue grafting and ex-vivo expanded Mesenchymal Stem Cells enriched adipose tissue grafting for the treatment of contour deformities with pigmentary changes on the face. Material and Methods: In this study, eighty (80) patients with contour deformities of the face with hyperpigmentation were recruited after informed consent. Two techniques i.e., conventional fat grafting (C-FG) and fat grafts enriched with expanded adipose stem cells (FG-ASCs), were used to address the pigmentation. Both techniques were explained to patients, and enrolled patients were divided into two groups i.e., C-FG and FG-ASCS, per patients’ choice and satisfaction. Patients of the FG-ASCs group were treated with fat grafts enriched with expanded adipose stem cells, while patients of the C-FGs group were treated with conventional fat grafting. Patients were followed for 12 months, and improvement in face pigmentation was assessed clinically as well as measured objectively. Patient satisfaction was also documented as highly satisfied, satisfied, and unsatisfied. Results: Mean age of patients was 24.42(±4.49), and 66 patients were females. The forehead was involved in 61.20% of cases, the cheek in 21.20% of cases, the chin in 11.20% of cases, and the nose in 6.20% of cases. In the GF-ASCs group, the integrated color density (ICD) was decreased (1.08×10⁶ ±4.64×10⁵) as compared to the C-FG group (2.80×10⁵±1.69×10⁵). Patients treated with fat grafts enriched with expanded adipose stem cells were significantly more satisfied as compared to patients treated with conventional fat grafting only. Conclusion: Mesenchymal stem cell-enriched autologous fat grafting is a preferred option for improving the contour deformities related to increased pigmentation of face skin.

Keywords: hyperpigmentation, color density, enriched adipose tissue graft, fat grafting, contour deformities, Image J

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Authors: Zellagui Rahima, Chaumont Denis, Boughelout Abderrahman, Adnane Mohamed

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Thin films of CdxZn1-xS were deposed by chemical bath deposition on glass substrates for photovoltaic applications. The thin films CdZnS were synthesized by chemical bath (CBD) with different deposition protocols for optimized the parameter of deposition as the temperature, time of deposition, concentrations of ion and pH. Surface morphology, optical and chemical composition properties of thin film CdZnS were investigated by SEM, EDAX, spectrophotometer. The transmittance is 80% in visible region 300 nm – 1000 nm; it has been observed in that films the grain size is between 50nm and 100nm measured by SEM image and we also note that the shape of particle is changing with the change in concentration. This result favors of application these films in solar cells; the chemical analysis with EDAX gives information about the presence of Cd, Zn and S elements and investigates the stoichiometry.

Keywords: thin film, solar cells, transmition, cdzns

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Authors: Diego Luján Villarreal

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Retinal prosthetic devices aim to repair some vision in visual impairment patients by stimulating electrically neural cells in the visual system. In this study, the 3D linear electrode carrier is presented. A simulation framework was developed by placing the 3D carrier 1 mm away from the fovea center at the highest-density cell. Cell stimulation is verified in COMSOL Multiphysics by developing a 3D computational model which includes the relevant retinal interface elements and dynamics of the voltage-gated ionic channels. Current distribution resulting from low threshold amplitudes produces a small volume equivalent to the volume confined by individual cells at the highest-density cell using small-sized electrodes. Delicate retinal tissue is protected by excessive charge density

Keywords: retinal prosthetic devices, visual devices, retinal implants., visual prosthetic devices

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Authors: Rayhana Begum, HongBin Wang, Nur Alam Siddiquee, Md.Yasin Ahmed

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Biotin treatment has significant effects on blood glucose, and pharmacological doses of biotin improve hyperglycemia. The present study was aimed to investigate the efficacy and safety of biotin in combination with canagliflozin in improving glycemic control on High Fat Diet-induced diabetes in Rats. Thirty male rats were divided into five groups (six rats /group): control, high fat diet (HFD), canagliflozin (CAG), biotin (BIO), and CAG + BIO. The treatments with CAG and /or BIO significantly reduced the body weight gain, blood glucose and HbA1c levels, whereas CAG in combination with BIO revealed greater glycemic improvement than CAG monotherapy. The treatment with CAG and /or BIO causes significant change in lipid profile and CK level while the treatment with CAG in combination with BIO showed better results as compared with CAG monotherapy. Furthermore, combination of biotin with CAG improved the pancreatic and cardiac damage when compared with other treated groups.

Keywords: canagliflozin, biotin, HbA1c, lipid profile

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

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Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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Authors: Kakali Bhadra

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Harmalol administration caused remarkable reduction in proliferation of HepG₂ cells with GI₅₀ of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 ^oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG₂ cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub G_o/G₁ population made the cancer cell, HepG₂, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

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Authors: Ming Ze Kao

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Static magnetic fields (SMF) are widely used in several medical applications, especially in diagnosis of tumors. However, biological effects of the SMFs on modulating cell physiology through the Lorentz force, which is highly frequency and magnitude dependent, remain to be elucidated. Specific patterns from SMFs of static MF, delivered by means of Halbach array magnets with a gradient increment of 6.857mT/mm from center to border, were found to have profound inhibitory effect on the growth rate of human cell line derived from Nasopharyngeal carcinoma patients. The SMFs, which were shown to be noncontact, selectively impact rapid dividing cells while quiescent cells stay intact. The phenomenon acts in two modes: the arrest of cell proliferation in the G2/M phase and destruction of cell mitosis in cell division. First mode is manifested by impacting the proper formation of mitotic spindle, whereas the second results in disintegration of the cancer cell. Both modes are demonstrated when SMF was applied for 24 hours to cancer cells, the results revealed that metaphase arrest during mitosis due to activation of DNA damage response (DDR), resulting in high expression of ATM-NBS1-CHEK signaling pathways and higher G2/M phase ratio compared with control group. Here, experimental data suggest that the SMFs cause activation of cell cycle checkpoints, which implies the MFs as a potential therapeutic modality as a sensitizer for radiotherapy or chemotherapy.

Keywords: static magnetic field, DNA damage response, Halbach array, magnetic therapy

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Authors: Muslim Idan Mohsin, Mohammed Jasim Al-Shamarti, Rusul Idan Mohsin, Ali A. Majeed

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One of the causative agents of the lower respiratory tract (LRT) is Pseudomonas aeruginosa, which can lead to severe infection associated with a lung infection. There are many cytokines that are secreted in response to bacterial infection, in particular interleukin IL-36 cytokine in response to P. aeruginosa infection. The involvement of IL-36 in the P. aeruginosa infection could be a clue to find a specific way for treatments of different inflammatory and degenerative lung diseases. IL36 promotes primary immune response via binding to the IL-36 receptor (IL-36R). Indeed, an overactivity of IL-36 might be an initiating factor for many immunopathologic sceneries in pneumonia. Here we demonstrate if the IL-36 cytokine increases in response P. aeruginosa infection that is isolated from lower respiratory tract infection (LRT). We demonstrated that IL-36 expression significantly unregulated in human lung epithelial (A549) cells after infected by P. aeruginosa at mRNA level.

Keywords: IL36, Pseudomonas aeruginosa, LRT infection, A549 cells

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Authors: Sabuj Kanti Mazumder, Mazlan Abd Ghaffar, Simon Kumar Das

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In this study, we analyzed the effects of water temperature and diet on the growth properties and gastric emptying period of juvenile Malabar blood snapper (Lutjanus malabaricus) over a 30day experimental period. Fish were collected from a local hatchery of Pulau Ketam, Selangor, Malaysia and immediately transferred to flow-through sea water system and subjected to four different temperatures (22, 26, 30, and 34 °C) and two diets (formulated pellet and shrimp). Body weight gain, food consumption, food conversion ratio, food consumption efficiency, specific growth rate, relative growth rate, daily growth rate, and gastric emptying period were significantly influenced by temperature and diet (P<0.05). The best food conversion ratio was with the shrimp group recorded at 30°C (1.33±0.08). The highest growth rate was observed in the shrimp group at 30°C (3.97±0.57% day-1), and the lowest was observed in the formulated pellet group at 22°C (1.63±0.29% day-1). No significant difference was observed between the groups subjected to temperatures of 26 and 30°C. Similarly, the lowest gastric emptying period was detected in the shrimp group at 30°C (16h), where the proportion of meal residues in the stomach decreased from 100% to less than 8% after 12h of starvation. A significantly longer gastric emptying period was observed in the formulated pellet group at 22°C (28h). Overall, the best results were observed on shrimp group subjected to a 30°C temperature. The data obtained from this study suggest that a shrimp diet fed on L. malabaricus at 30°C will optimize the commercial production of this commercially important fish species.

Keywords: aquaculture, diet, digestion rate, growth, Malabar blood snapper

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Authors: Sina Mahdavi

Abstract:

Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human immunodeficiency virus (HIV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on human HIV infection in MS disease progression. In this study, the keywords "Multiple sclerosis", "Human immunodeficiency virus ", and "Central nervous system" in the databases PubMed, and Google Scholar between 2017 and 2022 were searched and 15 articles were chosen, studied, and analyzed. Revealed histologic signs of "MS-like illness" in the setting of HIV, which comprised widespread demyelination with reactive astrocytes, foamy macrophages, and perivascular infiltration with inflammatory cells, all of which are compatible with MS lesions. Human immunodeficiency virus causes dysfunction of the immune system, especially characterized by hypergammaglobulinemia and chronic activation of B cells. Activation of B cells leads to increased synthesis of immunoglobulin and finally to an excess of free light chains. Free light chains may be involved in autoimmune responses against neurons. There is a high expression of HIV during the course of MS, which indicates the relationship between HIV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HIV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human immunodeficiency virus, central nervous system, autoimmunity

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