Pathogenic arterial remodeling: the good and bad of microRNAs

2013 ◽  
Vol 304 (8) ◽  
pp. H1050-H1059 ◽  
Author(s):  
Yuanyuan Wei ◽  
Andreas Schober ◽  
Christian Weber
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular Remodeling ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
In Vivo Studies ◽  
Functional Roles ◽  
Short Rnas ◽  
Complex Adaptive

A number of cardiovascular diseases, such as restenosis, aneurysm, and atherosclerosis, lead to vascular remodeling associated with complex adaptive reactions of different cell populations. These reactions include growth of smooth muscle cells, proliferation of endothelial cells, and the inflammatory response of macrophages. MicroRNAs (miRNAs), a class of short RNAs, play key roles in various biological processes and in the development of human disease by post-transcriptional regulation of gene expression. Here, we review the molecular mechanisms of a subset of miRNAs involved in vascular remodeling, including miR-143/145, miR-221/222, miR-126, miR-21, and miR-155. Some of these miRNAs, such as miR-143/145 and miR-126, have been shown to be protective during vascular remodeling, whereas others, such as miR-21, may promote the cellular response that leads to neointima formation. The increasing knowledge regarding the roles of miRNAs in vascular remodeling opens novel avenues for the treatment of various cardiovascular diseases. However, more in vivo studies on the functional roles of these miRNAs are required in the future.

scholarly journals The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3169
Author(s):  
Kevin Doello ◽  
Cristina Mesas ◽  
Francisco Quiñonero ◽  
Gloria Perazzoli ◽  
Laura Cabeza ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Sodium Selenite ◽  
Molecular Mechanisms ◽  
Combined Therapy ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
C57bl Mice ◽  
Migration Capacity

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.

scholarly journals Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms

2016 ◽  
Vol 7 ◽  
pp. 645-654 ◽  
Author(s):  
Bin Song ◽  
Yanli Zhang ◽  
Jia Liu ◽  
Xiaoli Feng ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Titanium Dioxide ◽  
Molecular Mechanisms ◽  
Titanium Dioxide Nanoparticles ◽  
Brain Dysfunction ◽  
In Vivo Studies ◽  
Cell Components ◽  
New Perspective ◽  
The Brain

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

Role of the ligand in intracellular receptor function: receptor affinity determines activation in vitro of the latent dioxin receptor to a DNA-binding form

1991 ◽  
Vol 11 (1) ◽  
pp. 401-411
Author(s):  
S Cuthill ◽  
A Wilhelmsson ◽  
L Poellinger
Keyword(s):  
Dna Binding ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Rank Order ◽  
Receptor Ligands ◽  
Free System ◽  
Dioxin Receptor

To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits signal- (dioxin-)induced activation of the latent cytosolic dioxin receptor to an active DNA-binding species. The DNA-binding properties of the in vitro-activated form were qualitatively indistinguishable from those of in vivo-activated nuclear receptor extracted from dioxin-treated cells. In vitro activation of the receptor by dioxin was dose dependent and was mimicked by other dioxin receptor ligands in a manner that followed the rank order of their relative affinities for the receptor in vitro and their relative potencies to induce target gene transcription in vivo. Thus, in addition to triggering the initial release of inhibition of DNA binding and presumably allowing nuclear translocation, the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.

scholarly journals An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 916 ◽  
Author(s):  
Salman Ul Islam ◽  
Muhammad Bilal Ahmed ◽  
Haseeb Ahsan ◽  
Mazharul Islam ◽  
Adeeb Shehzad ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Human Skin ◽  
Cancer Progression ◽  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
In Vivo Studies ◽  
Skin Malignancy ◽  
Dietary Phytochemicals

Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the advantages of key dietary phytochemicals in whole fruits and vegetables, their bioavailability, and underlying molecular mechanisms for preventing skin cancer. Current challenges and future prospects for research are also reviewed. To date, most of the chemoprevention investigations have been conducted preclinically, and additional clinical trials are required to conform and validate the preclinical results in humans.

scholarly journals Genetically Altered Mouse Models: the Good, the Bad, and the Ugly

2003 ◽  
Vol 14 (3) ◽  
pp. 154-174 ◽  
Author(s):  
Tamizchelvi Thyagarajan ◽  
Satish Totey ◽  
Mary Jo S. Danton ◽  
Ashok B. Kulkarni
Keyword(s):  
Gene Targeting ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Genetically Engineered ◽  
Murine Models ◽  
Functional Roles ◽  
Targeted Gene Disruption ◽  
Gene Knockout Mouse

Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment.

Cellular and molecular mechanisms of hypoxia-inducible factor driven vascular remodeling

2007 ◽  
Vol 97 (05) ◽  
pp. 774-787 ◽  
Author(s):  
Norbert Weissmann ◽  
Friedrich Grimminger ◽  
Werner Seeger ◽  
Frank Rose ◽  
Jörg Hänze
Keyword(s):  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Genetic Manipulation ◽  
Hypoxia Inducible Factor ◽  
Ischemic Disease ◽  
Hypoxic Conditions ◽  
Concomitant Reduction ◽  
Adaptive Processes

SummaryHypoxia-inducible factor (HIF) is an oxygen-dependent transcription factor that activates a diverse set of target genes, the products of which are involved in adaptive processes to hypoxia. Employing genetic manipulation of HIF expression, in-vivo and cellular studies have focused on HIF as a crucial factor affecting hypoxia-induced vascular remodeling.Vascular remodeling comprises processes which establish and improve blood vessel supply such as vasculogenesis, angiogenesis and arteriogenesis. These processes are observed during ontogenesis, tumor progression, ischemic disease or physical training. Furthermore, under hypoxic conditions, a pulmonary-specific type of vascular remodeling called pulmonary arterial remodeling occurs that is characterized by thickening of the vessel wall with a concomitant reduction in the vessel lumen area, thereby limiting blood flow.This response results in pulmonary hypertension with right ventricular hypertrophy, a lethal disease. In this review, we summarize and discuss mechanisms by which HIF interferes with the different vascular remodeling processes.

scholarly journals Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 596 ◽  
Author(s):  
María del Carmen Villegas-Aguilar ◽  
Álvaro Fernández-Ochoa ◽  
María de la Luz Cádiz-Gurrea ◽  
Sandra Pimentel-Moral ◽  
Jesús Lozano-Sánchez ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Phenolic Compounds ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Wide Range ◽  
High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

scholarly journals Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals—Illustrated with Four Actin Cytoskeleton Proteins

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 672 ◽  
Author(s):  
Zain Akram ◽  
Ishtiaq Ahmed ◽  
Heike Mack ◽  
Ramandeep Kaur ◽  
Richard C. Silva ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Molecular Mechanisms ◽  
Budding Yeast ◽  
Animal Cell ◽  
Molecular Genetic ◽  
In Vivo Studies ◽  
Yeast Saccharomyces Cerevisiae ◽  
Higher Eukaryotes

The budding yeast Saccharomyces cerevisiae has an actin cytoskeleton that comprises a set of protein components analogous to those found in the actin cytoskeletons of higher eukaryotes. Furthermore, the actin cytoskeletons of S. cerevisiae and of higher eukaryotes have some similar physiological roles. The genetic tractability of budding yeast and the availability of a stable haploid cell type facilitates the application of molecular genetic approaches to assign functions to the various actin cytoskeleton components. This has provided information that is in general complementary to that provided by studies of the equivalent proteins of higher eukaryotes and hence has enabled a more complete view of the role of these proteins. Several human functional homologues of yeast actin effectors are implicated in diseases. A better understanding of the molecular mechanisms underpinning the functions of these proteins is critical to develop improved therapeutic strategies. In this article we chose as examples four evolutionarily conserved proteins that associate with the actin cytoskeleton: (1) yeast Hof1p/mammalian PSTPIP1, (2) yeast Rvs167p/mammalian BIN1, (3) yeast eEF1A/eEF1A1 and eEF1A2 and (4) yeast Yih1p/mammalian IMPACT. We compare the knowledge on the functions of these actin cytoskeleton-associated proteins that has arisen from studies of their homologues in yeast with information that has been obtained from in vivo studies using live animals or in vitro studies using cultured animal cell lines.

scholarly journals Nutraceuticals for the Treatment of Diabetic Retinopathy

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 771 ◽  
Author(s):  
Maria Grazia Rossino ◽  
Giovanni Casini
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Vitreoretinal Surgery ◽  
In Vivo Studies ◽  
Early Diabetes ◽  
Advanced Stages ◽  
Endothelial Growth Factor

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.

Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

2019 ◽  
pp. 1-11
Author(s):  
A. F. Ogori ◽  
A. T. Girgih ◽  
J. O. Abu ◽  
M. O. Eke
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Food Sources ◽  
In Vivo Studies ◽  
Future Research ◽  
Target Cells

The bioactive peptides produced by enzymatic hydrolysis, acid hydrolysis and fermentation approach have been identified and used widely in research. These methods are important in enhancement or prevention and management of chronic diseases that are ravaging the world such as type -2-diabetes, hypertension, oxidative stress, cancer, and obesity. Sources of bioactive peptides have been established ranging from plant to animal and marine foods that have pharmacological effects; however these effects are dependent on target cells and peptides structure and conformations.  Plants such as hemp and animal source such as milk among others validate the findings of In vitro and In-vivo studies and the efficiency of these bioactive peptides in the management of certain chronic diseases. This article reviews the literature on bioactive peptides with concern on food sources, production and bioactive peptides application in enhancement of health and management of hypertension, diabetes and oxidative stress.  Future research efforts on bioactive peptides should be directed towards elucidating specific sequenced bioactive peptides and their molecular mechanisms, through In-vivo and In-vitro studies for specific health condition in human using nutrigenomics and peptideomic approaches.

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