Control of cellular division and development

1980 ◽  
Vol 14 (S4) ◽  
pp. 111-217
Keyword(s):  
2018 ◽  
Vol 25 (31) ◽  
pp. 3748-3767 ◽  
Author(s):  
Mohammed Benabdallah ◽  
Oualid Talhi ◽  
Fatiha Nouali ◽  
Nouredine Choukchou-Braham ◽  
Khaldoun Bachari ◽  
...  

The present review deals with the progress in medicinal chemistry of spirocyclic compounds, a wider class of natural and synthetic organic molecules, defined as a hybrid of two molecular entities covalently linked via a unique tetrahedral carbon. This spiro central carbon confers to the molecules a tridimensional structurally oriented framework, which is found in many medicinally relevant compounds, a well-known example is the antihypertensive spironolactone. Various bioactive natural products possess the privileged spiro linkage and different chemo-types thereof become synthetically accessible since the 20th century. Actually, there has been a growing interest in the synthesis of heterocyclic hybrids gathered via a spiro carbon. Most of these combinations are two moieties in one scaffold being able to interfere with biological systems through sequential mechanisms. Spirocyclic hybrids containing indole or oxindole units are compounds exhibiting higher interaction with biological receptors by protein inhibition or enzymatic pathways and their recognition as promising anticancer agents in targeted chemotherapy is foreseen. These specific, low-weight and noncomplex spirocyclic hybrids are potent inhibitors of SIRT1, Mdm2–p53 and PLK4, showing affinity for anaplastic lymphoma kinase (ALK) receptor. They are also known as excellent DNA binders, acting on cellular division by arresting the cell cycle at different phases and inducing apoptotic cell death. A structural diversity of spirocyclic hybrids has proved neuroprotective effects, anti-HIV, antiviral and antibacterial activities. Hundred of papers are mentioned in this review underlying chemical issues and pharmacological potencies of spiro compounds, which render them impressive synthetic hits for innovative drug conception.


Author(s):  
Lindsay Schneider ◽  
Anubhav Tripathi

Aneuploidy is caused by problems during cellular division and segregation errors during meiosis that lead to an abnormal number of chromosomes and initiate significant genetic abnormalities during pregnancy or the loss of a fetus due to miscarriage. Screening and diagnostic technologies have been developed to detect this genetic condition and provide parents with critical information about their unborn child. In this review, we highlight the complexities of aneuploidy as a disease as well as multiple technological advancements in testing that help to identify aneuploidy at various time points throughout pregnancy. We focus on aneuploidy diagnosis during preimplantation genetic testing that is performed during in vitro fertilization as well as prenatal screening and diagnosis during pregnancy. This review focuses on DNA-based analysis and laboratory techniques for aneuploidy detection through reviewing molecular- and engineering-based technical advancements. We also present key challenges in aneuploidy detection during pregnancy, including sample collection, mosaic embryos, economic factors, and the social implications of this testing. The goal of this review is to synthesize broad information about aneuploidy screening and diagnostic sample collection and analysis during pregnancy and discuss major challenges the field is still facing despite decades of advancements.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1084
Author(s):  
Ivan N. Ivanov ◽  
Vilém Zachleder ◽  
Milada Vítová ◽  
Maria J. Barbosa ◽  
Kateřina Bišová

An increase in temperature can have a profound effect on the cell cycle and cell division in green algae, whereas growth and the synthesis of energy storage compounds are less influenced. In Chlamydomonas reinhardtii, laboratory experiments have shown that exposure to a supraoptimal temperature (39 °C) causes a complete block of nuclear and cellular division accompanied by an increased accumulation of starch. In this work we explore the potential of supraoptimal temperature as a method to promote starch production in C. reinhardtii in a pilot-scale photobioreactor. The method was successfully applied and resulted in an almost 3-fold increase in the starch content of C. reinhardtii dry matter. Moreover, a maximum starch content at the supraoptimal temperature was reached within 1–2 days, compared with 5 days for the control culture at the optimal temperature (30 °C). Therefore, supraoptimal temperature treatment promotes rapid starch accumulation and suggests a viable alternative to other starch-inducing methods, such as nutrient depletion. Nevertheless, technical challenges, such as bioreactor design and light availability within the culture, still need to be dealt with.


Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2851-2858 ◽  
Author(s):  
Yukari Okamoto ◽  
Daniel C. Douek ◽  
Richard D. McFarland ◽  
Richard A. Koup

Abstract Immune reconstitution is a critical component of recovery after treatment of human immunodeficiency virus (HIV) infection, cancer chemotherapy, and hematopoietic stem cell transplantation. The ability to enhance T-cell production would benefit such treatment. We examined the effects of exogenous interleukin-7 (IL-7) on apoptosis, proliferation, and the generation of T-cell receptor rearrangement excision circles (TRECs) in human thymus. Quantitative polymerase chain reaction demonstrated that the highest level of TRECs (14 692 copies/10 000 cells) was present in the CD1a+CD3−CD4+CD8+stage in native thymus, suggesting that TREC generation occurred following the cellular division in this subpopulation. In a thymic organ culture system, exogenous IL-7 increased the TREC frequency in fetal as well as infant thymus, indicating increased T-cell receptor (TCR) rearrangement. Although this increase could be due to the effect of IL-7 to increase thymocyte proliferation and decrease apoptosis of immature CD3− cells, the in vivo experiments using NOD/LtSz-scid mice given transplants of human fetal thymus and liver suggested that IL-7 can also directly enhance TREC generation. Our results provide compelling evidence that IL-7 has a direct effect on increasing TCR-αβ rearrangement and indicate the potential use of IL-7 for enhancing de novo naı̈ve T-cell generation in immunocompromised patients.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 607
Author(s):  
Tsu-Man Chiu ◽  
Ping-Chun Hsu ◽  
Mohd Yaqub Khan ◽  
Cheng-An J. Lin ◽  
Chun-Hung Lee ◽  
...  

Warts are a common skin problem and are caused by infection with a virus. Warts are currently mainly treated by therapies involving ablating tissue or interrupting cellular division. However, all these existing treatments are either invasive or cause skin pain and tissue destruction. Imiquimod is a synthetic compound that belongs to the imidazoquinolinone family. It has been successfully used as a topical drug to treat external anogenital warts. However, topical imiquimod cream for warts is restricted by low skin permeability, and several side effects such as itching, pain, and erosions occur most frequently following topical treatment. Microneedle technology, a minimally invasive drug delivery system, has the potential to overcome the barrier of the stratum corneum. This technique would also offer a painless treatment choice and provide personalized therapies. In the study, we loaded imiquimod within dissolving microneedles using the molding method. Gelatin was used as a structural material for microneedle formation without adding a crosslinker. To our knowledge, this is the first study of using dissolving microneedles and exploring their utilization with imiquimod for the treatment of warts. First, we added fluorescent dye and trypan blue into the microneedles to evaluate the status of drugs in the microneedles and the degradation property of microneedles made of gelatin, respectively. Here we also prove the strength of the imiquimod microneedles and study their capability to penetrate the skin. The results show no apparent differences in mechanical failure after an additional imiquimod-loaded. Besides, we provide evidence that imiquimod microneedles induce secreted embryonic alkaline phosphatase (SEAP) in the RAW 264.7 macrophages. Gelatin does not affect the imiquimod in microneedles; a similar immune response was affected by the imiquimod alone or imiquimod complexed with gelatin. Our research demonstrates a proof of concept of using imiquimod microneedles for future warts treatment.


1943 ◽  
Vol 78 (4) ◽  
pp. 285-304 ◽  
Author(s):  
William F. Friedewald ◽  
Rubert S. Anderson

The virus-induced papillomas of cottontail as well as domestic rabbits regress completely within a few weeks when exposed to 5,000 r of x-ray irradiation. The x-rays do not immediately kill the papilloma cells, but lead to death by inhibiting cellular division and producing pathological changes in the cells which then continue to differentiate. The virus associated with the growths, however, not only persists in undiminished amount during regression, but often an increased yield of it can be obtained on extraction. The fibroma virus in crude extracts or in vivo is inactivated by far less irradiation than the papilloma virus. 10,000 r destroys 90 per cent or more of the infectivity of the fibroma virus, whereas at least 100,000 r is required to inactivate 50 per cent of the papilloma virus in extracts containing about the same amount of protein. No variant of the papilloma virus or fibroma virus has been encountered as a result of the irradiation.


2012 ◽  
Vol 22 (06) ◽  
pp. 1250003 ◽  
Author(s):  
THIERRY COLIN ◽  
ANGELO IOLLO ◽  
DAMIANO LOMBARDI ◽  
OLIVIER SAUT

A tumor growth model based on a parametric system of partial differential equations is considered. The system corresponds to a phenomenological description of a multi-species population evolution. A velocity field taking into account the volume increase due to cellular division is introduced and the mechanical closure is provided by a Darcy-type law. The complexity of the biological phenomenon is taken into account through a set of parameters included in the model that need to be calibrated. To this end, a system identification method based on a low-dimensional representation of the solution space is introduced. We solve several idealized identification cases corresponding to typical situations where the information is scarce in time and in terms of observable fields. Finally, applications to actual clinical data are presented.


2017 ◽  
Vol 23 (4) ◽  
pp. 453-480
Author(s):  
Erwan Bigan ◽  
Pierre Plateau

One proposed scenario for the emergence of biochemical oscillations is that they may have provided the basic mechanism behind cellular self-replication by growth and division. However, alternative scenarios not requiring any chemical oscillation have also been proposed. Each of the various protocell models proposed to support one or another scenario comes with its own set of specific assumptions, which makes it difficult to ascertain whether chemical oscillations are required or not for cellular self-replication. This article compares these two cases within a single whole-cell model framework. This model relies upon a membrane embedding a chemical reaction network (CRN) synthesizing all the cellular constituents, including the membrane, by feeding from an external nutrient. Assuming the osmolarity is kept constant, the system dynamics are governed by a set of nonlinear differential equations coupling the chemical concentrations and the surface-area-to-volume ratio. The resulting asymptotic trajectories are used to determine the cellular shape by minimizing the membrane bending energy (within an approximate predefined family of shapes). While the stationary case can be handled quite generally, the oscillatory one is investigated using a simple oscillating CRN example, which is used to identify features that are expected to hold for any network. It is found that cellular self-replication can be reached with or without chemical oscillations, and that a requirement common to both stationary and oscillatory cases is that a minimum spontaneous curvature of the membrane is required for the cell to divide once its area and volume are both doubled. The oscillatory case can result in a greater variety of cellular shape trajectories but raises additional constraints for cellular division and self-replication: (i) the ratio of doubling time to oscillation period should be an integer, and (ii) if the oscillation amplitude is sufficiently high, then the spontaneous curvature must be below a maximum value to avoid early division before the end of the cycle. Because of these additional stringent constraints, it is likely that early protocells did not rely upon chemical oscillations. Biochemical oscillations typical of modern evolved cells may have emerged later through evolution for other reasons (e.g., metabolic advantage) and must have required additional feedback mechanisms for such a self-replicating system to be robust against even slight environmental variations (e.g., temperature fluctuations).


2013 ◽  
Vol 31 (4) ◽  
pp. 793-804 ◽  
Author(s):  
C.B. Silva ◽  
E. Simionatto ◽  
S.S. Gebara ◽  
N.R. Poppi ◽  
A.C.S. Cândido ◽  
...  

The volatile oils extracted from the roots of Polygala extraaxillaris were analyzed to assess whether they increase oxidative stress in Brachiaria decumbens var. Piatã, as well as to assess their effect on cellular division and cytotoxicity in laboratory. Six concentrations were used (0%, 0.35%, 0.65%, 1.25%, 0.65%, and 5.0%) with four repetitions of 25 seeds. The substance 1-(2-hydroxyphenyl) - ethanone was identified as the major constituent of the volatile oils. The results showed that the highest concentrations of the oils resulted in an increase in the oxidative stress in B. decumbens, as well as alteration in germination and growth, with a consequent reduction in the process of cellular division, causing changes in the growth standard and antioxidant defense.


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