scholarly journals Potentiality, Limitations, and Consequences of Different Experimental Models to Improve Photodynamic Therapy for Cancer Treatment in Relation to Antiangiogenic Mechanism

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2118
Author(s):  
Martin Majerník ◽  
Rastislav Jendželovský ◽  
Peter Fedoročko

The relevance of experimentally gained information represents a long-term debating issue in the field of molecular biology research. The loss of original conditions in the in vitro environment affects various biological mechanisms and cellular interactions. Consequently, some biochemical mechanisms are lost or critically altered. Analyses in these modified conditions could, therefore, distort the relevancy of experimentally gained information. In some cases, the similarities with original conditions are so small that utilization of simpler in vitro models seems impossible, or could occur in a very limited way. To conclude, the study of more complex phenomena places higher demands on the complexity of the experimental model. The latest information highlights the fact that the tumor angiogenesis mechanism has very complex features. This complexity can be associated with a wide range of angiogenic factors expressed by a variety of malignant and non-malignant cells. Our article summarizes the results from various experimental models that were utilized to analyze a photodynamic therapy effect on tumor angiogenic mechanisms. Additionally, based on the latest information, we present the most important attributes and limitations of utilized experimental models. We also evaluate the essential problems associated with angiogenic mechanism induction after photodynamic therapy application.

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 609 ◽  
Author(s):  
Amjad Khan ◽  
Muhammad Ikram ◽  
Jong Ryeal Hahm ◽  
Myeong Ok Kim

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.


2021 ◽  
Vol 99 (4) ◽  
pp. 531-553 ◽  
Author(s):  
Cindrilla Chumduri ◽  
Margherita Y. Turco

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.


Blood ◽  
2020 ◽  
Vol 136 (22) ◽  
pp. 2535-2547 ◽  
Author(s):  
W. Grey ◽  
R. Chauhan ◽  
M. Piganeau ◽  
H. Huerga Encabo ◽  
M. Garcia-Albornoz ◽  
...  

Abstract Expansion of human hematopoietic stem cells (HSCs) is a rapidly advancing field showing great promise for clinical applications. Recent evidence has implicated the nervous system and glial family ligands (GFLs) as potential drivers of hematopoietic survival and self-renewal in the bone marrow niche; how to apply this process to HSC maintenance and expansion has yet to be explored. We show a role for the GFL receptor, RET, at the cell surface of HSCs in mediating sustained cellular growth, resistance to stress, and improved cell survival throughout in vitro expansion. HSCs treated with the key RET ligand/coreceptor complex, glial-derived neurotrophic factor and its coreceptor, exhibit improved progenitor function at primary transplantation and improved long-term HSC function at secondary transplantation. Finally, we show that RET drives a multifaceted intracellular signaling pathway, including key signaling intermediates protein kinase B, extracellular signal-regulated kinase 1/2, NF-κB, and p53, responsible for a wide range of cellular and genetic responses that improve cell growth and survival under culture conditions.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Claudia J. Labrador-Rached ◽  
Rebecca T. Browning ◽  
Laura K. Braydich-Stolle ◽  
Kristen K. Comfort

Due to their distinctive physicochemical properties, platinum nanoparticles (PtNPs) have emerged as a material of interest for a number of biomedical therapeutics. However, in some instances NP exposure has been correlated to health and safety concerns, including cytotoxicity, activation of cellular stress, and modification to normal cell functionality. As PtNPs have induced differential cellular responses in vitro, the goal of this study was to further characterize the behavior and toxicological potential of PtNPs within a HepG2 liver model. This study identified that a high PtNP dosage induced HepG2 cytotoxicity. However, lower, subtoxic PtNP concentrations were able to elicit multiple stress responses, secretion of proinflammatory cytokines, and modulation of insulin-like growth factor-1 dependent signal transduction. Taken together, this work suggests that PtNPs would not be overtly toxic for acute exposures, but sustained cellular interactions might produce long term health consequences.


1993 ◽  
Vol 264 (2) ◽  
pp. C457-C463 ◽  
Author(s):  
I. Dorup ◽  
T. Clausen

In young rats fed a Mg(2+)-deficient diet for 3 wk, Mg2+ and K+ contents in soleus and extensor digitorum longus muscles were significantly reduced and closely correlated. In isolated soleus muscles, Mg2+ depletion induced an even more pronounced loss of K+, and Mg2+ and K+ contents were correlated over a wide range (r = 0.95, P < 0.001). Extracellular Mg2+ (0-1.2 mM) caused no change in total or ouabain-suppressible 86Rb influx. After long-term incubation in Ca(2+)-Mg(2+)-free buffer with EDTA and EGTA, cellular Mg2+ and K+ contents were reduced by 35 and 15%, respectively, without any reduction in ATP and total or ouabain-suppressible 86Rb influx. In Mg(2+)-depleted muscles 42K efflux was increased by up to 42%, and repletion with Mg2+ produced a graded decrease. We conclude that Mg2+ and K+ contents are closely correlated in muscles Mg2+ depleted in vivo or in vitro and that neither extracellular nor moderate intracellular Mg2+ depletion affects total or Na(+)-K+ pump-mediated K+ influx. The reduced K+ content may rather be related to increased K+ efflux from the muscles.


2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 110-115 ◽  
Author(s):  
Susan Yung ◽  
Chan Tak Mao

♦ Background The introduction of peritoneal dialysis (PD) as a modality of renal replacement therapy has provoked much interest in the biology of the peritoneal mesothelial cell. Mesothelial cells isolated from omental tissue have immunohistochemical markers that are identical to those of mesothelial stem cells, and omental mesothelial cells can be cultivated in vitro to study changes to their biologic functions in the setting of PD. ♦ Method The present article describes the structure and function of mesothelial cells in the normal peritoneum and details the morphologic changes that occur after the introduction of PD. Furthermore, this article reviews the literature of mesothelial cell culture and the limitations of in vitro studies. ♦ Results The mesothelium is now considered to be a dynamic membrane that plays a pivotal role in the homeostasis of the peritoneal cavity, contributing to the control of fluid and solute transport, inflammation, and wound healing. These functional properties of the mesothelium are compromised in the setting of PD. Cultures of peritoneal mesothelial cells from omental tissue provide a relevant in vitro model that allows researchers to assess specific molecular pathways of disease in a distinct population of cells. Structural and functional attributes of mesothelial cells are discussed in relation to long-term culture, proliferation potential, age of tissue donor, use of human or animal in vitro models, and how the foregoing factors may influence in vitro data. ♦ Conclusions The ability to propagate mesothelial cells in culture has resulted, over the past two decades, in an explosion of mesothelial cell research pertaining to PD and peritoneal disorders. Independent researchers have highlighted the potential use of mesothelial cells as targets for gene therapy or transplantation in the search to provide therapeutic strategies for the preservation of the mesothelium during chemical or bacterial injury.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alexander P Browning ◽  
Jesse A Sharp ◽  
Ryan J Murphy ◽  
Gency Gunasingh ◽  
Brodie Lawson ◽  
...  

Tumour spheroids are common in vitro experimental models of avascular tumour growth. Compared with traditional two-dimensional culture, tumour spheroids more closely mimic the avascular tumour microenvironment where spatial differences in nutrient availability strongly influence growth. We show that spheroids initiated using significantly different numbers of cells grow to similar limiting sizes, suggesting that avascular tumours have a limiting structure; in agreement with untested predictions of classical mathematical models of tumour spheroids. We develop a novel mathematical and statistical framework to study the structure of tumour spheroids seeded from cells transduced with fluorescent cell cycle indicators, enabling us to discriminate between arrested and cycling cells and identify an arrested region. Our analysis shows that transient spheroid structure is independent of initial spheroid size, and the limiting structure can be independent of seeding density. Standard experimental protocols compare spheroid size as a function of time; however, our analysis suggests that comparing spheroid structure as a function of overall size produces results that are relatively insensitive to variability in spheroid size. Our experimental observations are made using two melanoma cell lines, but our modelling framework applies across a wide range of spheroid culture conditions and cell lines.


2018 ◽  
Vol 71 (21) ◽  
pp. 3444-3457 ◽  
Author(s):  
Nthabeleng Molupe ◽  
Balaji Babu ◽  
David O. Oluwole ◽  
Earl Prinsloo ◽  
John Mack ◽  
...  

Micromachines ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 18 ◽  
Author(s):  
Christopher A. Hesh ◽  
Yongzhi Qiu ◽  
Wilbur A. Lam

The microvasculature is the primary conduit through which the human body transmits oxygen, nutrients, and other biological information to its peripheral tissues. It does this through bidirectional communication between the blood, consisting of plasma and non-adherent cells, and the microvascular endothelium. Current understanding of this blood–endothelium interface has been predominantly derived from a combination of reductionist two-dimensional in vitro models and biologically complex in vivo animal models, both of which recapitulate the human microvasculature to varying but limited degrees. In an effort to address these limitations, vascularized microfluidics have become a platform of increasing importance as a consequence of their ability to isolate biologically complex phenomena while also recapitulating biochemical and biophysical behaviors known to be important to the function of the blood–endothelium interface. In this review, we discuss the basic principles of vascularized microfluidic fabrication, the contribution this platform has made to our understanding of the blood–endothelium interface in both homeostasis and disease, the limitations and challenges of these vascularized microfluidics for studying this interface, and how these inform future directions.


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