Invited Review: Effect of oxygen deprivation on cell cycle activity: a profile of delay and arrest

2003 ◽  
Vol 94 (5) ◽  
pp. 2068-2083 ◽  
Author(s):  
R. M. Douglas ◽  
G. G. Haddad
Keyword(s):  
Cell Cycle ◽  
Early Life ◽  
Current Knowledge ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Point Of View ◽  
Cell Cycles ◽  
Young Embryo ◽  
Dividing Cells ◽  
Effect Of Oxygen

One of the most fascinating fields that have emanated in the past few decades is developmental biology. This is not only the case from a research point of view but also from the angle of clinical care and treatment strategies. It is now well demonstrated that there are many diseases (some believe all diseases) that have their roots in embryogenesis or in early life, where nature and environment often team up to facilitate the genesis of disease. There is probably no better example to illustrate the interactions between nature and environment than in early life, as early as in the first several cell cycles. As will be apparent in this review, the cell cycle is a very regulated activity and this regulation is genetic in nature, with checkpoint proteins playing an important role in controlling the timing, the size, and the growth of daughter cells. However, it is also very clear, as will be discussed in this work, that the microenvironment of the first dividing cells is so important for the outcome of the organism. In this review, we will focus on the effect of one stress, that of hypoxia, on the young embryo and its cell division and growth. We will first review some of the cell cycle definitions and stages and then review briefly our current knowledge and its gaps in this area.

scholarly journals Nematode-Induced Endoreduplication in Plant Host Cells: Why and How?

2013 ◽  
Vol 26 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Janice de Almeida Engler ◽  
Godelieve Gheysen
Keyword(s):  
Cell Cycle ◽  
Current Knowledge ◽  
Giant Cells ◽  
Transformation Process ◽  
Host Cells ◽  
Cyst Nematodes ◽  
Plant Host ◽  
Root Cells ◽  
Cell Cycles ◽  
Feeding Sites

Plant-parasitic root-knot and cyst nematodes have acquired the ability to induce remarkable changes in host cells during the formation of feeding sites. Root-knot nematodes induce several multinucleate giant cells inside a gall whereas cyst nematodes provoke the formation of a multinucleate syncytium. Both strategies impinge on the deregulation of the cell cycle, involving a major role for endoreduplication. This review will first describe the current knowledge on the control of normal and aberrant cell cycles. Thereafter, we will focus on the role of both cell-cycle routes in the transformation process of root cells into large and highly differentiated feeding sites as induced by the phytoparasitic root-knot and cyst nematodes.

scholarly journals Pharmacological and Parenteral Nutrition-Based Interventions in Microvillus Inclusion Disease

2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Changsen Leng ◽  
Edmond H. H. M. Rings ◽  
Saskia N. de Wildt ◽  
Sven C. D. van IJzendoorn
Keyword(s):  
Parenteral Nutrition ◽  
Clinical Research ◽  
Alternative Treatment ◽  
Current Knowledge ◽  
Case Reports ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Secretory Diarrhea ◽  
Pharmacological Interventions ◽  
Recent Advances

Microvillus inclusion disease (MVID) is a rare inherited and invariably fatal enteropathy, characterized by severe intractable secretory diarrhea and nutrient malabsorption. No cure exists, and patients typically die during infancy because of treatment-related complications. The need for alternative treatment strategies is evident. Several pharmacological interventions with variable successes have been tried and reported for individual patients as part of their clinical care. Unfortunately, these interventions and their outcomes have remained hidden in case reports and have not been reviewed. Further, recent advances regarding MVID pathogenesis have shed new light on the outcomes of these pharmacological interventions and offer suggestions for future clinical research and trials. Hence, an inventory of reported pharmacological interventions in MVID, their rationales and outcomes, and a discussion of these in the light of current knowledge is opportune. Together with a discussion on MVID-specific pharmacokinetic, -dynamic, and -genetic concerns that pose unique challenges regarding pharmacological strategies, we envision that this paper will aid researchers and clinicians in their efforts to develop pharmacological interventions to combat this devastating disease.

scholarly journals Intracellular Dynamics of the Ubiquitin-Proteasome-System

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 367 ◽  
Author(s):  
Maisha Chowdhury ◽  
Cordula Enenkel
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Yeast Cells ◽  
Ubiquitin Chain ◽  
Dividing Cells ◽  
Ubiquitin Proteasome

The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum ( ER) membranes. In prolonged quiescence, proteasome granules drop off the nuclear envelopeNE / ER membranes and migrate as droplet-like entitiesstable organelles  throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells, which comprise the majority of our body’s cells.

scholarly journals Children’s Pain: A Mandate for Change

2001 ◽  
Vol 6 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Andrea L Brennan-Hunter
Keyword(s):  
Current Knowledge ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Medline Search ◽  
The Past ◽  
Key Word ◽  
Different Types ◽  
Pain Knowledge ◽  
Children's Pain ◽  
Effective Assessment

There have been tremendous research advances in the past 15 years in knowledge about children's pain, and strategies for recognizing and managing that pain. However, the clinical care of children in pain remains a challenge. Children's pain continues to be frequently unrecognized , dismissed or ineffectively managed. A loud call for change is being voiced by physicians, nurses, children and their families. A review of the literature was conducted to document this issue. Starting with a Medline search of the key word 'child* + pain' and continuing with a snowball technique, articles and resources addressing children's pain were collected. Resources presented or published after 1990 were particularly sought because they theoretically reflect both current knowledge about children's pain and the implementation of this knowledge in practice. Unfortunately, although information on pain is available to help children, in many instances, it is not being used. The purpose of the present paper is twofold -- to present an overview of current knowledge of children's pain, and factors that hinder its effective assessment and management; and to present a mandate for change. Children's postoperative pain is highlighted in this paper as an example of the gap between pain knowledge and clinical practice. Although treatment strategies differ across different types of pain, children's conditions and ages, the principles and mandate for change discussed in this paper are directly relevant to all categories of children's pain.

scholarly journals Intracellular Dynamics of the Ubiquitin-Proteasome-System

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 367 ◽  
Author(s):  
Maisha Chowdhury ◽  
Cordula Enenkel
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Yeast Cells ◽  
Ubiquitin Chain ◽  
Dividing Cells ◽  
Ubiquitin Proteasome

The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body’s cells.

scholarly journals Characterization of the nitroreductase/metronidazole suicide gene system as a safeguard for cell based therapies

2017 ◽  
Vol 10 (2) ◽  
Author(s):  
Miranda Li
Keyword(s):  
Cell Cycle ◽  
Thymidine Kinase ◽  
Spinal Cord Injuries ◽  
Embryonic Stem ◽  
Treatment Strategies ◽  
Suicide Gene ◽  
Confocal Imaging ◽  
Gene System ◽  
Dividing Cells ◽  
Cycle Indicator

Cell-based therapies are promising treatment strategies for a variety of disorders ranging from cancer to spinal cord injuries. However, there is a risk of the transplanted cells becoming malignant. As a safeguard against this, suicide gene systems can be implemented so that transplanted cells can be eliminated if necessary by administering a pro-drug. Herpes simplex virus thymidine kinase (HSV-tk) paired with the pro-drug ganciclovir (GCV) is one of the most studied suicide gene systems. However, it can only kill cells that are actively dividing. Here we characterize another suicide gene system, nitroreductase (NTR) with its pro-drug metronidazole (MNZ), to investigate where in the cell cycle the killing occurs, hypothesizing that it could become an ideal candidate for eliminating transplanted cells irrespective of their proliferative status. Murine embryonic stem cells were transfected with vectors expressingeither HSV-tk or NTR and treated with the corresponding pro-drug. Confocal imaging and FUCCI (fluorescent ubiquitination-based cell cycle indicator) were used to identify where in the cell cycle the drug was active. MNZ was found to kill both dividing and non-dividing cells whereas GCV killed only the dividing cells. These resultssuggest that the NTR system may be a valuable addition or complement to HSV-tkLes thérapies cellulaires sont des stratégies promettantes en tant que traitements pour une variété de maladies. Celles-ci incluent le cancer et les traumatismes médullaires. Cependant, il y a un risque que les cellules implantées puissent devenir malignes. Afin de prévenir cela, des systèmes de gènes suicides peuvent être utilisés afin d’éliminer les cellules implantées si nécessaires par l’administration d’une prodrogue. La thymidine kinase, une enzymetrouvée chez les patients atteint du virus de l’herpès simplex (HSV tk), utilisée en conjonction avec la prodrogue ganciclovir (GCV), est un des systèmes de gènes suicides les plus étudiés. Cependant, il peut seulement tuer les cellules qui se divisent activement. Ici, nous caractérisons un autre système de gènes suicidaires, nitroréductase (NTR) avec sa prodrogue metronidazole (MNZ), afin d’étudier à quel point dans le cycle cellulaire la tuerie se déroule. L’hypothèse est que ce système pourrait être un candidat idéal afin d’éliminer les cellules transplantées, peu importe leur statut prolifératif. Des cellules de souche embryonnaires murines ont été transfectées avecdes vecteurs qui exprimaient soit HSV- tk ou NTR et traitées avec la prodrogue correspondante. La microscopie confocale et le système FUCCI (pour fluorescent ubiquitination-based cell cycle indicator) ont été utilisés afin d’identifier le point du cycle pendant lequel la drogue était active. Il a été trouvé que MNZ tuait les cellules qui sedivisaient et qui ne se divisaient pas, alors que GCV tuait uniquement les cellules qui se divisent. Ces résultats suggèrent que le système NTR pourrait être une addition ou un complément utile à HSV-tk.

Generating asymmetry in a changing environment: cell cycle regulation in dimorphic alphaproteobacteria

2020 ◽  
Vol 401 (12) ◽  
pp. 1349-1363
Author(s):  
Muriel C. F. van Teeseling ◽  
Martin Thanbichler
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Current Knowledge ◽  
Response Regulator ◽  
Binding Activity ◽  
Cell Fates ◽  
Cell Cycles ◽  
Dna Binding Activity ◽  
Distinct Cell ◽  
Cycle Regulation

AbstractWhile many bacteria divide by symmetric binary fission, some alphaproteobacteria have strikingly asymmetric cell cycles, producing offspring that differs significantly in their morphology and reproductive state. To establish this asymmetry, these species employ a complex cell cycle regulatory pathway based on two-component signaling cascades. At the center of this network is the essential DNA-binding response regulator CtrA, which acts as a transcription factor controlling numerous genes with cell cycle-relevant functions as well as a regulator of chromosome replication. The DNA-binding activity of CtrA is controlled at the level of both protein phosphorylation and stability, dependent on an intricate network of regulatory proteins, whose function is tightly coordinated in time and space. CtrA is differentially activated in the two (developing) offspring, thereby establishing distinct transcriptional programs that ultimately determine their distinct cell fates. Phase-separated polar microdomains of changing composition sequester proteins involved in the (in-)activation and degradation of CtrA specifically at each pole. In this review, we summarize the current knowledge of the CtrA pathway and discuss how it has evolved to regulate the cell cycle of morphologically distinct alphaproteobacteria.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Targeting Non-Oncogene Addiction for Cancer Therapy

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 129
Author(s):  
Hae Ryung Chang ◽  
Eunyoung Jung ◽  
Soobin Cho ◽  
Young-Jun Jeon ◽  
Yonghwan Kim
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Therapy ◽  
Cell Cycle Regulation ◽  
Synthetic Lethality ◽  
Current Knowledge ◽  
Cancer Therapies ◽  
Oncogene Addiction ◽  
Clinical Biomarkers ◽  
Cycle Regulation

While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of TONSL as a novel gene for targeted therapy. Although it is a scaffold protein with no known enzymatic activity, the strategy used for developing PCNA inhibitors can also be utilized to target TONSL. This review summarizes current knowledge on non-oncogene addiction, and the utilization of synthetic lethality for developing novel inhibitors targeting non-oncogenic addiction for cancer therapy.

scholarly journals Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1392
Author(s):  
Hidaya A. Kader ◽  
Muhammad Azeem ◽  
Suhib A. Jwayed ◽  
Aaesha Al-Shehhi ◽  
Attia Tabassum ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Food Allergies ◽  
Th2 Response ◽  
Therapeutic Outcomes ◽  
Environmental Agents ◽  
Novel Treatment Strategies

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.

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