scholarly journals Hydroxyurea—The Good, the Bad and the Ugly

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1096
Author(s):  
Marcelina W. Musiałek ◽  
Dorota Rybaczek
Keyword(s):  
Cancer Progression ◽  
Specific Interaction ◽  
Interaction Mechanism ◽  
Myeloproliferative Disorders ◽  
Prolonged Treatment ◽  
Actual State ◽  
Cytotoxic Effects ◽  
Factors Affecting ◽  
Cell Cycles ◽  
Practical Applications

Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the cycle by inducing replication stress. It is a well-known and widely used drug, one which has proved to be effective in treating chronic myeloproliferative disorders and which is considered a staple agent in sickle anemia therapy and—recently—a promising factor in preventing cognitive decline in Alzheimer’s disease. The reversibility of HU-induced replication inhibition also makes it a common laboratory ingredient used to synchronize cell cycles. On the other hand, prolonged treatment or higher dosage of hydroxyurea causes cell death due to accumulation of DNA damage and oxidative stress. Hydroxyurea treatments are also still far from perfect and it has been suggested that it facilitates skin cancer progression. Also, recent studies have shown that hydroxyurea may affect a larger number of enzymes due to its less specific interaction mechanism, which may contribute to further as-yet unspecified factors affecting cell response. In this review, we examine the actual state of knowledge about hydroxyurea and the mechanisms behind its cytotoxic effects. The practical applications of the recent findings may prove to enhance the already existing use of the drug in new and promising ways.

scholarly journals Silver Nanoparticles and Their Antibacterial Applications

2021 ◽  
Vol 22 (13) ◽  
pp. 7202
Author(s):  
Tamara Bruna ◽  
Francisca Maldonado-Bravo ◽  
Paul Jara ◽  
Nelson Caro
Keyword(s):  
Silver Nanoparticles ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Secondary Effects ◽  
Cytotoxic Effects ◽  
Factors Affecting ◽  
Gram Positive Bacteria ◽  
Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

scholarly journals Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2473
Author(s):  
Jang Mi Han ◽  
Jae Kyung Sohng ◽  
Woo-Haeng Lee ◽  
Tae-Jin Oh ◽  
Hye Jin Jung
Keyword(s):  
Gastric Cancer ◽  
Protein Kinase ◽  
Cancer Progression ◽  
Biological Activities ◽  
Specific Interaction ◽  
Cyclophilin A ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ags Cells ◽  
In Silico Docking

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.

Cytotoxic effects of cisplatin, cis-dichlorodiammineplatinum(II), on Tetrahymena

1988 ◽  
Vol 90 (4) ◽  
pp. 707-716
Author(s):  
J.R. Nilsson
Keyword(s):  
Mitochondrial Membrane ◽  
Prolonged Treatment ◽  
Dependent Manner ◽  
Inner Mitochondrial Membrane ◽  
Cell Organelles ◽  
Cell Content ◽  
Cytotoxic Effects ◽  
Dense Granules ◽  
High Concentrations ◽  
Dose Dependent

A study was made of the effects of cisplatin, cis-dichlorodiammineplatinum(II) (5–250 mg l-1), on the physiology and fine structure of Tetrahymena. The physiological effects observed were dose-dependent. Endocytosis was inhibited reversibly in all, but late in the high, concentrations. After an initial dose-related increase, due to division of cells most advanced in the cell cycle, proliferation ceased for at least two normal cell generations (6 h) in 50 and 100 mg drug l-1, but for 24 h in 250 mg l-1, after which multiplication was resumed in a dose-dependent manner. Exposure to cisplatin resulted in the appearance of small, refractive granules and platinum (i.e. electron-dense material) accumulated in these granules. Fine structural observations of cells exposed to 250 mg drug l-1 showed nucleolar fusion and appearance initially of lipid droplets, dense granules and autophagosomes. A time-dependent redistribution of cell organelles was revealed by morphometry; in particular, the mitochondria increased in number, but decreased in size. Moreover, after prolonged treatment (24 h) and without cell division, the inner mitochondrial membrane had diminished and the ratio of the inner to the outer mitochondrial membrane was only half of the value for control mitochondria. Concomitantly with this decrease, the cell content of ATP was reduced to a similar extent. The findings indicate a specific action of cisplatin on mitochondria, resembling that induced in Tetrahymena by chloramphenicol and methotrexate.

scholarly journals Application of Cross-Hole Tomography for Assessment of Soil Stabilization by Grout Injection

Geosciences ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 399 ◽  
Author(s):  
Mikhail Lebedev ◽  
Kirill Dorokhin
Keyword(s):  
Seismic Tomography ◽  
Urban Areas ◽  
Soil Stabilization ◽  
Geophysical Methods ◽  
Negative Influence ◽  
Actual State ◽  
Existing Buildings ◽  
Practical Applications ◽  
Geotechnical Monitoring ◽  
Urban Conditions

Currently, the spread of megalopolises poses an ever-increasing necessity for underground space development for the purpose of the arrangement of transport communications, underground parking areas, trade areas, etc. The implementation of such projects entails a significant increase in the risk of accidents and damage to existing buildings within construction activity influence areas. The reduction of the risk of accidents during the construction of underground facilities within urban areas may only become possible with the identification of adverse factors negatively influencing existing buildings or a facility under erection and elaboration (to reduce such negative influence). The application of geophysical methods in complex assessments of the actual state of an encompassing mass significantly increases efficiency and the credibility of geotechnical monitoring. The application of seismic tomography significantly increases the resolution capability of surveys. Existing techniques, e.g., seismic tomography, allow for any depths to be investigated at a high resolution, even given constricted urban conditions. This article covers the practical applications of seismic tomography in qualitative assessments of actions and an efficiency evaluation of the injective stabilization of soil.

scholarly journals Assessment of Language and Literacy in Children Who Are d/Deaf and Hard of Hearing

2019 ◽  
Vol 9 (3) ◽  
pp. 223 ◽  
Author(s):  
Lianna Pizzo ◽  
Amanda Chilvers
Keyword(s):  
Hard Of Hearing ◽  
Language And Literacy ◽  
Theoretical Orientations ◽  
Factors Affecting ◽  
Research And Practice ◽  
Practical Applications ◽  
Children’S Participation ◽  
Children's Participation ◽  
The Relationship

This article presents theoretical orientations and practical applications for the assessment of d/Deaf and hard of hearing (d/Dhh) children. It discusses current approaches to assessment and the factors affecting d/Dhh children’s participation in assessments using those approaches. Gaps in the field around access to appropriate assessments are discussed. This review also shares information on the relationship between the purpose of the assessment and the approach selected. Basic considerations for both d/Deaf and hard of hearing multilingual learners (d/DMLs) and d/Dhh children with additional disabilities will be addressed. Finally, general recommendations are made for research and practice.

scholarly journals Role of Glutathione in Cancer Progression and Chemoresistance

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nicola Traverso ◽  
Roberta Ricciarelli ◽  
Mariapaola Nitti ◽  
Barbara Marengo ◽  
Anna Lisa Furfaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Cytotoxic Effects ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Glutathione Disulphide ◽  
Increased Susceptibility

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents.

scholarly journals Accounting for Model Error in Variational Data Assimilation: A Deterministic Formulation

2010 ◽  
Vol 138 (9) ◽  
pp. 3369-3386 ◽  
Author(s):  
Alberto Carrassi ◽  
Stéphane Vannitsem
Keyword(s):  
Data Assimilation ◽  
Deterministic Model ◽  
Model Error ◽  
Variational Data Assimilation ◽  
Noise Model ◽  
Actual State ◽  
Strong Constraint ◽  
Variational Assimilation ◽  
Uncorrelated Noise ◽  
Practical Applications

Abstract In data assimilation, observations are combined with the dynamics to get an estimate of the actual state of a natural system. The knowledge of the dynamics, under the form of a model, is unavoidably incomplete and model error affects the prediction accuracy together with the error in the initial condition. The variational assimilation theory provides a framework to deal with model error along with the uncertainties coming from other sources entering the state estimation. Nevertheless, even if the problem is formulated as Gaussian, accounting for model error requires the estimation of its covariances and correlations, which are difficult to estimate in practice, in particular because of the large system dimension and the lack of enough observations. Model error has been therefore either neglected or assumed to be an uncorrelated noise. In the present work, an approach to account for a deterministic model error in the variational assimilation is presented. Equations for its correlations are first derived along with an approximation suitable for practical applications. Based on these considerations, a new four-dimensional variational data assimilation (4DVar) weak-constraint algorithm is formulated and tested in the context of a linear unstable system and of the three-component Lorenz model, which has chaotic dynamics. The results demonstrate that this approach is superior in skill to both the strong-constraint and a weak-constraint variational assimilation that employs the uncorrelated noise model error assumption.

The Influence of Frictional Heating on the Sliding Friction of Elastomers and Polymers

1988 ◽  
Vol 61 (1) ◽  
pp. 119-136 ◽  
Author(s):  
C. M. McC. Ettles ◽  
Jui Hsieh Shen
Keyword(s):  
Sliding Friction ◽  
Frictional Heating ◽  
Surface Friction ◽  
Convincing Evidence ◽  
Phase Lag ◽  
Stick Slip ◽  
Factors Affecting ◽  
Practical Applications ◽  
Tan Δ ◽  
Approach Zero

Abstract The friction of polymers and elastomers has been widely researched, both in practical applications and in fundamental experiments. Although some of the basic mechanisms of elastomer friction have been well explored, the effect of frictional heating has not received much attention. This is surprising since the low thermal conductivity of elastomers can result in quite high temperatures being generated at the interface. This paper is concerned specifically with the influence of heat generation on the level of friction at the interface. Some present theories of elastomer friction are well established. The important factors that govern friction are considered to be the strength of interface bonds and the loss tangent, tan δ, where δ is the phase lag between harmonically applied strain and the stress response. On a rough surface, friction is considered to occur from hysteretic losses. On a smooth surface, friction is considered to occur from the formation of bonds across the interface, the extension of the bonds and their eventual fracture. In several quantitative models of elastomer friction summarized by Moore and Geyer, the result for friction is directly proportional to tan δ, thus for a perfectly elastic material, the friction (according to these models) tends to approach zero. Factors affecting the interface bond strength are somewhat better understood, Schallamach proposed that the bonds were molecular. This allowed an Eyring-type rate process theory to be applied, as illustrated with great clarity by Grosch. Grosch showed that the Williams-Landel-Ferry transformation could be applied to condense the friction-speed characteristics measured at various temperatures to a single “master curve.” These experiments gave convincing evidence that rubber friction is a thermally activated, molecular kinetic, stick-slip process. Grosch's experiments were later confirmed by Ludema and Tabor.

scholarly journals Histopathological changes induced by methotrexate in bone and bone marrow of male and female white mice

2011 ◽  
Vol 10 (2) ◽  
pp. 90
Author(s):  
K. G. Chelab And S. Kh. Majeed
Keyword(s):  
Bone Marrow ◽  
Dose Group ◽  
Chemotherapeutic Agents ◽  
Prolonged Treatment ◽  
Control Group ◽  
Histopathological Changes ◽  
Cytotoxic Effects ◽  
Toxic Dose ◽  
Body Weights ◽  
Group 5

The present study was conducted on 40 females and males white mice of approximately the same ages (4-6 weeks) and body weights (23-25 gm), for the aim of observing the toxic effects and histopathological changes on bones of mice due to prolonged treatment (6 months) with anticancer chemotherapeutic agents namely methotrexate. Forty mice were divided into 4 equal groups (10 mice of each group – 5 mice per sex). The first group (low or therapeutic dose group) was received 0.15 mg/ kg, I/M once weekly. The second group (intermediate dose group) received 0.30 mg/kg, I/M once weekly. The third (toxic dose group) received 0.45 mg/kg I/M once weekly. The fourth group was a control group, it received 0.2 ml buffered normal saline, I/M once weekly.The results showed Methotrexate can cause osteoporosis and bone marrow suppression, due to cytotoxic effects of it on bone marrow.

scholarly journals Factors affecting orthodontic treatment time and how to predict it

2021 ◽  
Author(s):  
Rania Adel Mitwally ◽  
Laila Marzooq Alesawi ◽  
Adhwaa Yahya Humedi ◽  
Saleh Saeed Al Baaltahin ◽  
Yara Ahmed Saeedi ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Orthodontic Treatment ◽  
Treatment Time ◽  
Treatment Plan ◽  
Prolonged Treatment ◽  
Large Set ◽  
Factors Affecting ◽  
Underlying Condition ◽  
Level Of Satisfaction ◽  
Speed Up

Orthodontic treatment time has been associated with certain parameters that can affect the different aspects of treatment regards to the patient and orthodontist. Therefore, a large set of research has focused on studying these factors. Many factors have been proposed in the literature as significant predictors for prolonged orthodontic treatment duration. In general, these factors are related to the patient, orthodontist, procedure, and severity of the underlying condition. Acquiring more knowledge about these factors can help orthodontists speed up the treatment plan, which might enhance the treatment outcomes and enhance the levels of satisfaction. In the current study, we have provided updated evidence regarding the different factors affecting orthodontic treatment time according to evidence from studies in the literature. Many factors were reported, including factors related to the procedure and the underlying condition, and factors related to the patient and orthodontist. Increasing knowledge and experience of the orthodontist might increase the level of satisfaction as it has been reported to significantly reduce the treatment duration. However, this should be accompanied by adequate patient compliance, which was also reported to be a significant predictor for prolonged treatment duration. Investigating the application of recent modalities that can speed up the treatment plan is not adequately validated, indicating the need for future validating studies.

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