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Influence of Cryptorchidism on Leydig Cell Function
Published in Tom O. Abney, Brooks A. Keel, The Cryptorchid Testis, 2020
There is growing evidence for the existence of a relationship between Leydig cells and other testicular cell types (see Chapter 8). It has been postulated that Leydig cell function is controlled to some extent by factors (paracrine substances) from the seminiferous tubules (either germ cells or Sertoli cells). Thus, a series of complex cell-cell interactions are believed to exist, in which function by one cell type is influenced by one or several other cell types. Leydig cell function is conceivably regulated by germ cells, Sertoli cells, myoid cells, and/or other cells. It follows, then, that cryptorchid-induced damage to the tubular compartment can alter this intercellular regulation. This raises the interesting question as to whether cryptorchid-induced changes in Leydig cell function are primary in nature or represent secondary alterations which result from altered paracrine regulatory mechanisms.
Progress in Antimalarial Drug Discovery and Development
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Anna C.C. Aguiar, Wilian A. Cortopassi, Antoniana U. Krettli
Several methods are applied to discover new transmission blocking approaches, such as targeting the P. falciparum stage V gametocytes, responsible for parasite transmission, aiming to discover drugs with gametocytocidal activity, e.g., PQ (2) and its derivatives, or MEFAS, a new compound in pre-clinical stages derived from MQ (9) and ART (4) (Aguiar et al. 2017, de Pilla Varotti et al. 2008, Penna-Coutinho et al. 2016). The ‘gold-standard’ laboratory assay for measuring transmission blocking is a membrane-feeding assay (SMFA). It embraces the complex cell biology of the parasite, the complex interactions of the parasites with the mosquito midgut microflora and the immune system of the mosquito. Unfortunately, it remains a very-low-throughput assay and prohibitively expensive for any HTS (Aguiar et al. 2017, Churcher et al. 2012, Miura et al. 2013).
Mycobacterium
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Verlaine J. Timms, Brett Anthony Neilan
The Mycobacteriaceae are aerobic, catalase positive and are considered Gram positive. Their main characteristic is that they are acid alcohol fast due to their waxy cell wall. It is the complex cell wall that significantly affects their growth, pathogenicity, resistance to bacteriocides, and survival. In all mycobacteria, the peptidoglycan layer is surrounded by a hydrophobic arabinogalactan-peptidoglycan-mycolic acid layer (Figure 19.1). In the M. avium complex (MAC), this layer is surrounded by a second electron dense layer, made up, in part, of serovar-specific glycopeptidolipid (ssGPL)1–6 that consists of core nonspecific GPL modified by serovar-specific oligosaccharide side chains. The core nonspecific GPL is common to many environmental mycobacteria and has a tetrapeptide structure linked to a 6-deoxy-L-talose which in MAC is further modified with variable oligosaccharide structures to form ssGPL.7,8
In vivo toxicity evaluation of nanoemulsions for drug delivery
Published in Drug and Chemical Toxicology, 2021
Mariana Appel Hort, Barbara da Silva Alves, Osmar Vieira Ramires Júnior, Mariana Correa Falkembach, Gabriela de Moraes Soares Araújo, Caroline Lopes Feijo Fernandes, Ronan Adler Tavella, Juliana Bidone, Cristiana Lima Dora, Flavio Manoel Rodrigues da Silva Júnior
In vitro experimental models are important for preliminary investigation and provide valuable information, but they are insufficient to predict potential human hazards (Ojer et al.2015). Studies that evaluate the toxicity of unloaded NLs using animals are still scarce in the scientific literature. Some important issues may be linked to this low number of toxicological studies. In vivo tests involve ethical issues and are time-consuming and expensive. On the other hand, in vitro assays are faster, convenient, less expensive, and devoid of any ethical issues. However, the complex cell–cell and cell–matrix interactions, the diversity of cell types, and hormonal effects present in vivo are all missing from cultured cellular systems. Moreover, in some cases it may be difficult to find the vehicle suitable for administration in vivo and to avoid nanoparticles aggregation (Dhawan and Sharma 2010). These factors associated with the absence of a clear regulatory guideline on the testing/evaluation of nanoparticle materials can lead to the low number of studies for toxicological evaluation in vivo.
Anti-melanogenic effects of extracellular vesicles derived from plant leaves and stems in mouse melanoma cells and human healthy skin
Published in Journal of Extracellular Vesicles, 2020
Ruri Lee, Hae Ju Ko, Kimin Kim, Yehjoo Sohn, Seo Yun Min, Jeong Ah Kim, Dokyun Na, Ju Hun Yeon
Unlike most eukaryotic cells, plants have complex cell walls that constitute a significant barrier to the movement of exosomes. Therefore, exosomes released from plant cells pass through a series of fusions of multivesicular bodies with the plasma membrane. The secretory products released by the plant secretions are deposited in a periplasmic space adjacent to the plasma membrane; as they accumulate, they create a pressure that permits a flux of secretions across the cell wall barrier. Thus, secreted substances, including exosomes, can be released without an energy requirement [33–35]. The size of plant-derived EVs was similar to or larger than that of naturally occurring animal cell exosomes, and was similar to that observed for sunflower apoplastic fluids (50–200 nm) and EVs derived from Arabidopsis rosette (50–300 nm) [36,37]. The efficiency of cellular uptake is considered a key factor in determining therapeutic efficacy because the targets of many therapeutic agents are located in intracellular compartments [38]. Therefore, we identified the optimal time and concentration for the absorption by melanoma cells and observed that both LEVs and SEVs were rapidly transferred to melanoma cells within 12 h.
Image-based multi-scale mechanical analysis of strain amplification in neurons embedded in collagen gel
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2019
Victor W. L. Chan, William R. Tobin, Sijia Zhang, Beth A. Winkelstein, Victor H. Barocas, Mark S. Shephard, Catalin R. Picu
Major barriers to a realistic representation of complex cell geometry include the generation for a model geometry from experimentally measured images and the subsequent mesh generation on that model geometry. Furthermore, the number of degrees of freedom required to properly represent the complex cell geometry is large, and when coupled with a multi-scale framework that is required to model the fibrous architecture of the extracellular matrix, the computational demand can become prohibitive. In this work, we addressed some of those challenges by developing a multi-scale model of a group of neurons embedded within a collagenous matrix. The objective in this work was to develop a general modeling strategy in which (1) confocal microscopy or another three-dimensional imaging modality is used to generate a realistic representation of a complex cell geometry, (2) that geometric model, along with the surrounding extracellular matrix, is converted to a finite-element mesh, (3) a multi-scale model is implemented on that mesh using a network microstructural model at each Gauss point (Chandran and Barocas 2007; Stylianopoulos and Barocas 2007), and (4) the solution of the mechanics problem is used to determine the distribution of strains within the cell, i.e. at a scale and with a resolution that is not accessible to direct microscopic observations.