scholarly journals DNA curvature and flexibility in vitro and in vivo

2010 ◽  
Vol 43 (1) ◽  
pp. 23-63 ◽  
Author(s):  
Justin P. Peters ◽  
L. James Maher
Keyword(s):  
Historical Context ◽  
Dna Curvature ◽  
Polymer Model ◽  
Exciting Field ◽  
Chain Polymer ◽  
New Methods ◽  
Active Research ◽  
Fundamental Forces

AbstractIt has been more than 50 years since the elucidation of the structure of double-helical DNA. Despite active research and progress in DNA biology and biochemistry, much remains to be learned in the field of DNA biophysics. Predicting the sequence-dependent curvature and flexibility of DNA is difficult. Applicability of the conventional worm-like chain polymer model of DNA has been challenged. The fundamental forces responsible for the remarkable resistance of DNA to bending and twisting remain controversial. The apparent ‘softening’ of DNA measured in vivo in the presence of kinking proteins and superhelical strain is incompletely understood. New methods and insights are being applied to these problems. This review places current work on DNA biophysics in historical context and illustrates the ongoing interplay between theory and experiment in this exciting field.

scholarly journals Production and Application of Multicistronic Constructs for Various Human Disease Therapies

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 580 ◽  
Author(s):  
Alisa A. Shaimardanova ◽  
Kristina V. Kitaeva ◽  
Ilmira I. Abdrakhmanova ◽  
Vladislav M. Chernov ◽  
Catrin S. Rutland ◽  
...  
Keyword(s):  
Human Diseases ◽  
Cellular Biology ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
New Methods ◽  
In Vivo Experiments ◽  
Mutant Genes ◽  
Methods Of Treatment

The development of multicistronic vectors has opened up new opportunities to address the fundamental issues of molecular and cellular biology related to the need for the simultaneous delivery and joint expression of several genes. To date, the examples of the successful use of multicistronic vectors have been described for the development of new methods of treatment of various human diseases, including cardiovascular, oncological, metabolic, autoimmune, and neurodegenerative disorders. The safety and effectiveness of the joint delivery of therapeutic genes in multicistronic vectors based on the internal ribosome entry site (IRES) and self-cleaving 2A peptides have been shown in both in vitro and in vivo experiments as well as in clinical trials. Co-expression of several genes in one vector has also been used to create animal models of various inherited diseases which are caused by mutations in several genes. Multicistronic vectors provide expression of all mutant genes, which allows the most complete mimicking disease pathogenesis. This review comprehensively discusses multicistronic vectors based on IRES nucleotide sequence and self-cleaving 2A peptides, including its features and possible application for the treatment and modeling of various human diseases.

scholarly journals Helicases FANCJ, RTEL1 and BLM Act on Guanine Quadruplex DNA in Vivo

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 870 ◽  
Author(s):  
Peter Lansdorp ◽  
Niek van Wietmarschen
Keyword(s):  
Gene Expression ◽  
Genome Stability ◽  
Cell Function ◽  
Historical Context ◽  
Telomere Maintenance ◽  
Dna Structures ◽  
G4 Dna ◽  
Guanine Quadruplex

Guanine quadruplex (G4) structures are among the most stable secondary DNA structures that can form in vitro, and evidence for their existence in vivo has been steadily accumulating. Originally described mainly for their deleterious effects on genome stability, more recent research has focused on (potential) functions of G4 structures in telomere maintenance, gene expression, and other cellular processes. The combined research on G4 structures has revealed that properly regulating G4 DNA structures in cells is important to prevent genome instability and disruption of normal cell function. In this short review we provide some background and historical context of our work resulting in the identification of FANCJ, RTEL1 and BLM as helicases that act on G4 structures in vivo. Taken together these studies highlight important roles of different G4 DNA structures and specific G4 helicases at selected genomic locations and telomeres in regulating gene expression and maintaining genome stability.

scholarly journals The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1473
Author(s):  
Mohamed Zaiou
Keyword(s):  
Rna Binding ◽  
Metabolic Diseases ◽  
Rna Binding Proteins ◽  
In Vivo Studies ◽  
Future Research ◽  
Circular Rnas ◽  
Exciting Field ◽  
Rna Molecules

Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs function as master regulators of gene expression by influencing both transcription and translation processes. Mechanistically, circRNAs are predicted to act as endogenous microRNA (miRNA) sponges, interact with functional RNA-binding proteins (RBPs), and associate with elements of the transcriptional machinery in the nucleus. Evidence is mounting that dysregulation of circRNAs is closely related to the occurrence of a range of diseases including cancer and metabolic diseases. Indeed, there are several reports implicating circRNAs in cardiovascular diseases (CVD), diabetes, hypertension, and atherosclerosis. However, there is very little research addressing the potential role of these RNA transcripts in the occurrence and development of obesity. Emerging data from in vitro and in vivo studies suggest that circRNAs are novel players in adipogenesis, white adipose browning, obesity, obesity-induced inflammation, and insulin resistance. This study explores the current state of knowledge on circRNAs regulating molecular processes associated with adipogenesis and obesity, highlights some of the challenges encountered while studying circRNAs and suggests some perspectives for future research directions in this exciting field of study.

scholarly journals Cellular MR Imaging

2005 ◽  
Vol 4 (3) ◽  
pp. 153535002005051 ◽  
Author(s):  
Michel Modo ◽  
Mathias Hoehn ◽  
Jeff W.M. Bulte
Keyword(s):  
Mr Imaging ◽  
Contrast Agents ◽  
Immune Cell ◽  
Late Phase ◽  
Superparamagnetic Iron Oxide ◽  
Cell Trafficking ◽  
Macrophage Activity ◽  
Active Research

Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall) superparamagnetic iron oxide [(U)SPIO] particles or (polymeric) paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (U)SPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune) cell trafficking and of novel guided (stem) cell-based therapies aimed to be translated to the clinic in the future.

scholarly journals The Bacterial Cytoskeleton

2006 ◽  
Vol 70 (3) ◽  
pp. 729-754 ◽  
Author(s):  
Yu-Ling Shih ◽  
Lawrence Rothfield
Keyword(s):  
Research Field ◽  
Cytoskeletal Proteins ◽  
Ordered Structures ◽  
Intermediate Filament Proteins ◽  
Plasmid Partition ◽  
Active Research ◽  
Division Cell ◽  
The Mind

SUMMARY In recent years it has been shown that bacteria contain a number of cytoskeletal structures. The bacterial cytoplasmic elements include homologs of the three major types of eukaryotic cytoskeletal proteins (actin, tubulin, and intermediate filament proteins) and a fourth group, the MinD-ParA group, that appears to be unique to bacteria. The cytoskeletal structures play important roles in cell division, cell polarity, cell shape regulation, plasmid partition, and other functions. The proteins self-assemble into filamentous structures in vitro and form intracellular ordered structures in vivo. In addition, there are a number of filamentous bacterial elements that may turn out to be cytoskeletal in nature. This review attempts to summarize and integrate the in vivo and in vitro aspects of these systems and to evaluate the probable future directions of this active research field.

scholarly journals The use of confocal microscopy in experimental studies and clinical practice of an endocrinologist: modern opportunities

2019 ◽  
Vol 65 (3) ◽  
pp. 174-183
Author(s):  
Natalya G. Mokrysheva ◽  
Sergey L. Kiselev ◽  
Natalia V. Klementieva ◽  
Anna M. Gorbacheva ◽  
Ivan I. Dedov
Keyword(s):  
Confocal Microscopy ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Imaging Method ◽  
New Methods ◽  
Corneal Confocal Microscopy ◽  
Endocrine Ophthalmopathy ◽  
Fundamental Research

Confocal microscopy is a modern imaging method that provides ample opportunities for in vitro and in vivo research. The clinical part of the review focuses on well-established techniques, such as corneal confocal microscopy for the diagnosis of diabetic neuropathy or endocrine ophthalmopathy; new methods are briefly described (intraoperative evaluation of tissues obtained by removing pituitary adenomas, thyroid and parathyroid glands). In the part devoted to fundamental research, the use of confocal microscopy to characterize the colocalization of proteins, as well as three-dimensional intracellular structures and signaling pathways in vivo, is considered. Indicators of intracellular calcium are analyzed.

scholarly journals The role of herbal medicine in the treatment of chronic tonsillitis

2020 ◽  
pp. 36-43 ◽  
Author(s):  
G. S. Maltseva ◽  
S. A. Karpishchenko
Keyword(s):  
Herbal Product ◽  
Chronic Tonsillitis ◽  
Phagocytic Index ◽  
Comprehensive Treatment ◽  
Immunological Parameters ◽  
New Methods ◽  
Walnut Leaves ◽  
Multiresistant Strains

The article presents our own research data on systemic immunity status in patients with chronic tonsillitis (CT) and microbiological profile of the flora isolated from the tonsils in CT. The study showed that phagocytic index in neutrophils decreased by 81.9% and the phagocytosis in neutrophils reduced by 67.2% in patients with CT. We studied microbial flora of the tonsils and its persistent properties in CT. The steps for that were as follows: we evaluated the antilysocyme (ALA), anti-interferon (AIA), anticomplementary (ACA) activities of the isolated microorganisms as possible ways to stand against the oxygen-independent mechanism of phagocytosis. Most strains of Staphylococcus aureus had ALA, AIA and AСA, while most strains of Streptococcus pyogenes had ALA, less frequently AСA and did not show AIA. We found antibacterial polyresistance in 56.0% of pathogens among the selected strains in the examined patients with CT. A comparative analysis of species antibiotic resistance showed that the largest number of multiresistant strains were S.aureus - 62.0%. The set of revealed persistent properties of chronic tonsillitis pathogens serves as underlying rationale for the search for new methods of therapy using drugs of non-antibacterial origin, affecting the factors of bacteria resistance to inborn and acquired immunity. It is possible, and necessary that attention be paid to phytotherapy in the search for such new methods. Tonsilgon N is one of the complex phytotherapeutic products, which efficacy and safety has been proven in clinical trials, and the main pharmacological properties are confirmed in in vitro and in vivo preclinical studies. It contains marshmallow root, chamomile flowers, horsetail grass, walnut leaves, yarrow grass, oak bark, and dandelion grass. The clinical studies revealed that it has positive effect on the dynamics of both clinical and microbiological, immunological parameters in patients with chronic tonsillitis. All these things allow us to recommend that this complex herbal product be more often included into the comprehensive treatment of chronic tonsillitis. 

scholarly journals Hypes and Hopes of Stem Cell Therapies in Dentistry: a Review

2022 ◽  
Author(s):  
Alessandra Rodriguez y Baena ◽  
Andrea Casasco ◽  
Manuela Monti
Keyword(s):  
Stem Cells ◽  
Temporal Dynamics ◽  
3D Cell Culture ◽  
Basic Research ◽  
Science Research ◽  
Dental Stem Cells ◽  
Exciting Field ◽  
Cell Therapies

AbstractOne of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies. Graphical abstract

Nanomaterials for Deep Tumor Treatment.

2020 ◽  
Vol 20 ◽  
Author(s):  
Daria Yu. Kirsanova ◽  
Zaira M. Gadzhimagomedova ◽  
Aleksey Yu. Maksimov ◽  
Alexander V. Soldatov
Keyword(s):  
Visible Light ◽  
Tumor Treatment ◽  
Internal Organs ◽  
X Ray ◽  
Synthesis Of Nanoparticles ◽  
New Methods ◽  
In Vivo Experiments ◽  
Uv Visible

: According to statistics, cancer is the second leading cause of death in the world. Thus, it is important to try to solve this medical and social problem by developing new methods for cancer treatment. An alternative to more wellknown approaches, such as radiotherapy and chemotherapy, is photodynamic therapy (PDT) which is limited to the shallow tissue penetration (< 1 cm) of visible light. Since the PDT process can be initiated in deep tissues by X-ray irradiation (X-ray induced PDT, or XPDT), it has a great potential to treat tumors in internal organs. The article discusses the principles of therapies. The main focus being on various nanoparticles used with or without photosensitizers, which allow the conversion of X-ray irradiation into UV-visible light. Much attention is given to the synthesis of nanoparticles and analysis of their characteristics such as size and spectral features. The results of in vitro and in vivo experiments are also discussed.

Molecular Modeling Approaches for the Prediction of Selected Pharmacokinetic Properties

2019 ◽  
Vol 18 (26) ◽  
pp. 2230-2238 ◽  
Author(s):  
Emilio S. Petito ◽  
David J.R. Foster ◽  
Michael B. Ward ◽  
Matthew J. Sykes
Keyword(s):  
Molecular Modeling ◽  
In Silico ◽  
Volume Of Distribution ◽  
Future Directions ◽  
Unbound Fraction ◽  
Drug Candidates ◽  
New Methods ◽  
Pharmacokinetic Properties

Poor profiles of potential drug candidates, including pharmacokinetic properties, have been acknowledged as a significant hindrance to the development of modern therapeutics. Contemporary drug discovery and development would be incomplete without the aid of molecular modeling (in-silico) techniques, allowing the prediction of pharmacokinetic properties such as clearance, unbound fraction, volume of distribution and bioavailability. As with all models, in-silico approaches are subject to their interpretability, a trait that must be balanced with accuracy when considering the development of new methods. The best models will always require reliable data to inform them, presenting significant challenges, particularly when appropriate in-vitro or in-vivo data may be difficult or time-consuming to obtain. This article seeks to review some of the key in-silico techniques used to predict key pharmacokinetic properties and give commentary on the current and future directions of the field.

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