Background: The essential trace element and micronutrient selenium exerts most of its biological actions through incorporation into selenoproteins as selenocysteine. Two further types of Se-containing proteins exist, including those that have selenomethionine incorporated instead of methionine, and the group of selenium-binding proteins. We previously described an ortholog of selenium-binding protein 1 (SELENBP1) in the nematode Caenorhabditis elegans, Y37A1B.5, and demonstrated that it confers resistance to toxic selenite concentrations while impairing general stress resistance and life expectancy of C. elegans.
Objective: We tested for the effect of selenite on Y37A1B.5 expression, and we analyzed whether Y37A1B.5 also shows a lifespan-modulating effect when the nematodes are deficient in the selenoenzyme thioredoxin reductase-1 (TRXR-1).
Methods: C. elegans expressing a translational reporter construct encoding GFP-tagged Y37A1B.5 under the control of the Y37A1B.5 promoter were exposed to selenite, followed by fluorescence microscopic analysis of GFP levels. Lifespan analyses and RNA interference experiments were performed in trxr-1-deficient worms.
Results: We here demonstrate that selenite at toxic concentrations stimulates the expression of the translational Y37A1B.5 reporter. The lifespan-extending effect of Y37A1B.5 deficiency was preserved upon the deletion of the only selenoprotein in C. elegans, TRXR-1.
Conclusion: These data suggest that (1) Y37A1B.5 may serve as a selenite-responsive buffer against high environmental selenium concentrations and that (2) lifespan extension elicited by Y37A1B.5 knockdown does not require functional TRXR-1. To read out more, please visit:https://www.eurekaselect.com/179267/article
Background: The complexity of follicular fluid metabolome presents a huge challenge for qualitative and quantitative metabolite profiling and discovery of the comprehensive biomarkers.
Objective: In order to address this challenge, novel SWATHtoMRM metabolomics method was used for providing broad coverage and excellent quantitative capability to discover the human follicular fluid metabolites related to age and evaluate their relationship with pregnancy outcome and oocyte senescence.
Methods: The patients were divided into four groups according to age, including group A (28 cases, 21- 27 years old), group B (42 cases, 28-34 years old), group C (31 cases, 35-41 years old), and group D (24 cases, 42-48 years old). Follicular fluid samples from 125 IVF patients were analyzed. The differential ions among the four groups were identified by principal components analysis according to accurate mass, isotope ratio, and tandem mass spectroscopic spectra. Then, the differential metabolic pathways were further identified by a KEGG cluster analysis.
Results: A total of 18 metabolites in the follicular fluid differed among the four groups, including amino acids, lipids, hormones, and vitamins. A total of 15 metabolites, including 6-oxohexanoate, phenylalanine, proline, hexadecanoic acid, linoleate, arachidonate, oleic acid, docosahexaenoic acid, LysoPC(16:1), LysoPC(20:5), LysoPC (20:3), 25-hydroxyvitamin D3, 5-dehydroepisterol, 27- hydroxycholesterol, and 5beta-cholestane-3alpha,7alpha,12alpha,23,25-pentol, were down-regulated with age and 3 metabolites, including LysoPC(18:3), LysoPC(18:1), and 13,14-dihydroretinol, were upregulated with age.
Conclusion: Our study provides useful information for revealing the relationship between age and female reproductive capability.
Author(s): Abbas A. Ridha, Soheila Kashanian*, Abbas H. Azandaryani, Ronak Rafipour, Elahe Mahdavian.
Aims: In the present work, folic acid-modified human serum albumin conjugated to cationic solid lipid nanoparticles were synthesized as nanocarriers of mitoxantrone for the treatment of breast cancer.
Background: Dual-targeted drug delivery is a new drug dosing strategy that is frequently used to enhance the therapeutic efficacy of anticancer drugs.
Objective: Dual targeting of the cancer cells was achieved by dual tagging of human serum albumin and folic acid on the surface of the lipid nanoparticles.
Methods: The targeted drug-loaded nanocomplexes were synthesized and characterized using transmission electron microscopy along with photon-correlation and Fourier-transform infrared spectroscopic techniques. The anti-cancer activity of the nanocomplexes was screened against an in-vitro model of MCF-7 and MDA-MB-231 breast cancer cell lines to examine drug efficacy.
Results: The entrapment efficiency and drug loading values for mitoxantrone were calculated to be 97 and 8.84%, respectively. The data from the drug release studies for the system indicated the release profile did not significantly change within a pH range of 5.5-7.4. The hemolysis ratio of the hybrid carrier was less than 5% even at the upper doses of 3 mg/mL, demonstrating its safety for intravenous injection with limited hemolysis and a long blood circulation time.
Conclusion: The cell cytotoxicity results confirmed that the drug hybrid nanocomplex was more toxic to breast cancer cells compared with the free drug. Furthermore, the weakly cationic and small size particles prevented opsonin binding of nanocomplexes, improving blood circulation time and cancer tissue uptake. To read out more, please visit: http://www.eurekaselect.com/node/176690
Resistance to chemotherapy and relapse are major hurdles for the effective treatment of cancer. Major reason for this is a small sub population of cancer stem cells (CSCs) and its microenvironment. CSCs are critical driving force for several types of cancer, such as gastric, colon, breast and many more. Hence, for the complete eradication of cancer, it is necessary to develop therapeutic approaches that can specifically target CSCs. Chemical agents that target different proteins involved in CSC signaling pathways, either as single agent or simultaneously targeting two or more proteins have generated promising pre-clinical and clinical results. In the current review article, we have discussed various targets and cellular pathways that can be explored for the effective and complete eradication of CSCs. Some latest developments in the field of design, synthesis and screening of ligands to target cancer stem cells have been summarized in the current review article. To read out more, please visit: http://www.eurekaselect.com/174388/article
Author(s):Ramesh Akkina, Daniel L. Barber, Moses T. Bility, Karl-Dimiter Bissig, Benjamin J. Burwitz, Katrin Eichelberg, Janice J. Endsley, J. Victor Garcia, Richard Hafner, Petros C. Karakousis, Brent E. Korba, Rajen Koshy, Chris Lambros, Stephan Menne, Eric L. Nuermberger, Alexander Ploss, Brendan K. Podell, Larisa Y. Poluektova, Brigitte E. Sanders-Beer*, Selvakumar Subbian, Angela Wahl.
The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Welldesigned small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.
Author(s): Meiqi Wu, Yingxi Yang, Hui Wang, Jun Ding, Huan Zhu, Yan Xu*.
Background: With the rapid development of biological research, microRNAs (miRNAs) have increasingly attracted worldwide attention. The increasing biological studies and scientific experiments have proven that miRNAs are related to the occurrence and development of a large number of key biological processes which cause complex human diseases. Thus, identifying the association between miRNAs and disease is helpful to diagnose the diseases. Although some studies have found considerable associations between miRNAs and diseases, there are still a lot of associations that need to be identified. Experimental methods to uncover miRNA-disease associations are time-consuming and expensive. Therefore, effective computational methods are urgently needed to predict new associations.
Methodology: In this work, we propose an integrated method for predicting potential associations between miRNAs and diseases (IMPMD). The enhanced similarity for miRNAs is obtained by combination of functional similarity, gaussian similarity and Jaccard similarity. To diseases, it is obtained by combination of semantic similarity, gaussian similarity and Jaccard similarity. Then, we use these two enhanced similarities to construct the features and calculate cumulative score to choose robust features. Finally, the general linear regression is applied to assign weights for Support Vector Machine, K-Nearest Neighbor and Logistic Regression algorithms.
Results: IMPMD obtains AUC of 0.9386 in 10-fold cross-validation, which is better than most of the previous models. To further evaluate our model, we implement IMPMD on two types of case studies for lung cancer and breast cancer. 49 (Lung Cancer) and 50 (Breast Cancer) out of the top 50 related miRNAs are validated by experimental discoveries.
Conclusion: We built a software named IMPMD which can be freely downloaded from https:// github.com/Sunmile/IMPMD.
Background: The mitochondrion is a multi-functional organelle that is mainly responsible for energy supply in the mammalian cells. Over 100 human diseases are attributed to mitochondrial dysfunction. Mitochondrial therapy (mitotherapy) aims to transfer functional exogenous mitochondria into mitochondria-defective cells for recovery of the cell viability and consequently, prevention of the disease progress.
Objective: The review summarizes the evidence on exogenous mitochondria that can directly enter mammalian cells for disease therapy following local and intravenous administration, and suggests that when healthy cells donate their mitochondria to damaged cells, the mitochondrial transfer between cells serve as a new mode of cell rescue. Then the transferred mitochondria play their roles in recipient cells, including energy production and maintenance of cell function.
Conclusion: Mitotherapy makes the of modulation of cell survival possible, and it would be a potential therapeutic strategy for mitochondrial diseases.
Author(s):Angela Tartaglia, Marcello Locatelli, Victoria Samanidou*.
Background: Biopharmaceuticals are biological drugs consisting of a complex compound that can be produced by a living organism or derive from it. Biopharmaceuticals are very complicated compounds from structural point of view and for this reason, they cannot be fully characterized in terms of their structure with current analytical methods as it happens instead of low molecular weight chemicals drugs.
Introduction: The regulatory guidelines require the characterization of the primary or higher sequence of these molecules and the characterization of any post-translational modifications. The use of biopharmaceuticals has really grown in the last few years: in 2016, the number of biopharmaceuticals approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for use in humans’ diseases was 1357. From 2013 to 2016, 73 of these compounds were approved for the treatment of cancer, inflammation, immune disorders, infections, anemia and cardiovascular diseases.
Aim/Conclusion: The aim of the present review is to provide an overview of recent approaches for the characterization of biopharmaceutical products in HPLC that have been presented in the literature in the last years. To read out more, please visit: http://www.eurekaselect.com/168075/article
Background: Genetic drugs have aroused much attention in the past twenty years. RNA interference (RNAi) offers novel insights into discovering potential gene functions and therapies targeting genetic diseases. Small interference RNA (siRNA), typically 21-23 nucleotides in length, can specifically degrade complementary mRNA. However, targeted delivery and controlled release of siRNA remain a great challenge.
Methods: Different types of lipid-based delivery vehicles have been synthesized, such as liposomes, lipidoids, micelles, lipoplexes and lipid nanoparticles. These carriers commonly have a core-shell structure. For active targeting, ligands may be conjugated to the surface of lipid particles.
Results: Lipid-based drug delivery vehicles can be utilized in anti-viral or anti-tumor therapies. They can also be used to tackle genetic diseases or discover novel druggable genes.
Conclusion: In this review, the structures of lipid-based vehicles and possible surface modifications are described, and applications of delivery vehicles in biomedical field are discussed.To read out more, please visit: http://www.eurekaselect.com/175085/article
Background: Spinosin is one of the major bioactive constituents among the total flavonoids in semen ziziphi spinosae, which has sedation and hypnosis actions.
Methods: A simple and rapid high-resolution ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was developed and validated for predicting the structures of its spinosin metabolic products. This paper presents the first research focused on the metabolites of spinosin in human liver microsomes.
Results: Based on the analytical strategy, 8 spinosin metabolites were detected in human liver microsome incubation samples, and the metabolic pathways required to generate these metabolites were proposed. However, no phase II metabolites were found. The cytochrome P450 enzyme is the main metabolic enzyme involved in drug metabolism, accounting for approximately 75% of the total number of different metabolic reactions.
Conclusion: The in vitro metabolism of spinosin was proposed. These results allow us to learn about spinosin metabolism, leading to a better understanding of drug biotransformation and providing a basis for clinical applications. Moreover, this study laid the foundation for developing new pharmaceutical drugs. To read out more, please visit: http://www.eurekaselect.com/165902/article