scholarly journals Manipulation of Axonal Outgrowth via Exogenous Low Forces

2020 ◽  
Vol 21 (21) ◽  
pp. 8009
Author(s):  
Sara De Vincentiis ◽  
Alessandro Falconieri ◽  
Vincenzo Scribano ◽  
Samuele Ghignoli ◽  
Vittoria Raffa
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Special Focus ◽  
Axonal Outgrowth ◽  
Non Invasive ◽  
Neurite Initiation ◽  
Applied Forces ◽  
And Control ◽  
Regenerative Therapies

Neurons are mechanosensitive cells. The role of mechanical force in the process of neurite initiation, elongation and sprouting; nerve fasciculation; and neuron maturation continues to attract considerable interest among scientists. Force is an endogenous signal that stimulates all these processes in vivo. The axon is able to sense force, generate force and, ultimately, transduce the force in a signal for growth. This opens up fascinating scenarios. How are forces generated and sensed in vivo? Which molecular mechanisms are responsible for this mechanotransduction signal? Can we exploit exogenously applied forces to mimic and control this process? How can these extremely low forces be generated in vivo in a non-invasive manner? Can these methodologies for force generation be used in regenerative therapies? This review addresses these questions, providing a general overview of current knowledge on the applications of exogenous forces to manipulate axonal outgrowth, with a special focus on forces whose magnitude is similar to those generated in vivo. We also review the principal methodologies for applying these forces, providing new inspiration and insights into the potential of this approach for future regenerative therapies.

scholarly journals Apoptosis-reactivating agents for targeted anticancer therapy

2013 ◽  
Vol 59 (2) ◽  
pp. 119-143 ◽  
Author(s):  
A.A. Philchenkov
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Chemotherapeutic Drugs ◽  
Promising Candidate ◽  
Non Invasive ◽  
Key Factor ◽  
Apoptotic Pathways

The current knowledge on molecular mechanisms of apoptosis is presented focusing on the key elements of the extrinsic death receptor pathway as well as the intrinsic mitochondrial pathway. Disregulation of apoptotic pathways is considered as a key factor in the survival of cancer cells in response to conventional chemotherapeutic drugs or radiation therapy. Substances that selectively reactivate apoptosis in malignant cells are the promising candidate anticancer drugs, which have now entered various phases of clinical trials. The up-to-date techniques allowing for non-invasive in vivo visualization of apoptotic cells with special reference to therapy-induced cell death are briefly surveyed.

scholarly journals Rho GTPases as Key Molecular Players within Intestinal Mucosa and GI Diseases

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 66
Author(s):  
Rashmita Pradhan ◽  
Phuong A. Ngo ◽  
Luz d. C. Martínez-Sánchez ◽  
Markus F. Neurath ◽  
Rocío López-Posadas
Keyword(s):  
Intestinal Mucosa ◽  
Rho Gtpases ◽  
Current Knowledge ◽  
Cell Types ◽  
Effector Proteins ◽  
Special Focus ◽  
Specific Cell ◽  
Rho Proteins

Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.

scholarly journals In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2348
Author(s):  
Leon Riehakainen ◽  
Chiara Cavallini ◽  
Paolo Armanetti ◽  
Daniele Panetta ◽  
Davide Caramella ◽  
...  
Keyword(s):  
Imaging Modality ◽  
Imaging Techniques ◽  
Special Focus ◽  
Tissue Remodelling ◽  
Biodegradable Implant ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Positron Emission ◽  
Longitudinal Imaging

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.

scholarly journals Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lingyu Yang ◽  
Dehai Xian ◽  
Xia Xiong ◽  
Rui Lai ◽  
Jing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Cost ◽  
Natural Agents ◽  
Molecular Damage ◽  
And Control

Proanthocyanidins (PCs) are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerousin vitroandin vivostudies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, anti-inflammation, immunomodulation, DNA repair, and antitumor activity. Accumulation of prooxidants such as reactive oxygen species (ROS) exceeding cellular antioxidant capacity results in oxidative stress (OS), which can damage macromolecules (DNA, lipids, and proteins), organelles (membranes and mitochondria), and whole tissues. OS is implicated in the pathogenesis and exacerbation of many cardiovascular, neurodegenerative, dermatological, and metabolic diseases, both through direct molecular damage and secondary activation of stress-associated signaling pathways. PCs are promising natural agents to safely prevent acute damage and control chronic diseases at relatively low cost. In this review, we summarize the molecules and signaling pathways involved in OS and the corresponding therapeutic mechanisms of PCs.

scholarly journals Recent Advances in Surface Nanoengineering for Biofilm Prevention and Control. Part I: Molecular Basis of Biofilm Recalcitrance. Passive Anti-Biofouling Nanocoatings

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1230 ◽  
Author(s):  
Paul Cătălin Balaure ◽  
Alexandru Mihai Grumezescu
Keyword(s):  
Life Cycle ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Current Knowledge ◽  
Emergent Properties ◽  
Bacterial Cells ◽  
Life Cycle Stages ◽  
Fouling Release ◽  
Biofilm Development ◽  
And Control

Medical device-associated infections are becoming a leading cause of morbidity and mortality worldwide, prompting researchers to find new, more effective ways to control the bacterial colonisation of surfaces and biofilm development. Bacteria in biofilms exhibit a set of “emergent properties”, meaning those properties that are not predictable from the study of free-living bacterial cells. The social coordinated behaviour in the biofilm lifestyle involves intricate signaling pathways and molecular mechanisms underlying the gain in resistance and tolerance (recalcitrance) towards antimicrobial agents as compared to free-floating bacteria. Nanotechnology provides powerful tools to disrupt the processes responsible for recalcitrance development in all stages of the biofilm life cycle. The present paper is a state-of-the-art review of the surface nanoengineering strategies currently used to design antibiofilm coatings. The review is structurally organised in two parts according to the targeted biofilm life cycle stages and molecular mechanisms intervening in recalcitrance development. Therefore, in the present first part, we begin with a presentation of the current knowledge of the molecular mechanisms responsible for increased recalcitrance that have to be disrupted. Further, we deal with passive surface nanoengineering strategies that aim to prevent bacterial cells from settling onto a biotic or abiotic surface. Both “fouling-resistant” and “fouling release” strategies are addressed as well as their synergic combination in a single unique nanoplatform.

scholarly journals Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 193 ◽  
Author(s):  
Yasuyoshi Miyata ◽  
Yohei Shida ◽  
Tomoaki Hakariya ◽  
Hideki Sakai
Keyword(s):  
Prostate Cancer ◽  
Green Tea ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tea Polyphenols ◽  
Green Tea Polyphenols ◽  
Anti Cancer ◽  
Prevention And Treatment

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.

scholarly journals Heavily Armed Ancestors: CRISPR Immunity and Applications in Archaea with a Comparative Analysis of CRISPR Types in Sulfolobales

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1523
Author(s):  
Isabelle Anna Zink ◽  
Erika Wimmer ◽  
Christa Schleper
Keyword(s):  
Comparative Analysis ◽  
Molecular Mechanisms ◽  
Model Organisms ◽  
Special Focus ◽  
Natural Environments ◽  
Type I ◽  
Accessory Proteins ◽  
Type Iii

Prokaryotes are constantly coping with attacks by viruses in their natural environments and therefore have evolved an impressive array of defense systems. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is an adaptive immune system found in the majority of archaea and about half of bacteria which stores pieces of infecting viral DNA as spacers in genomic CRISPR arrays to reuse them for specific virus destruction upon a second wave of infection. In detail, small CRISPR RNAs (crRNAs) are transcribed from CRISPR arrays and incorporated into type-specific CRISPR effector complexes which further degrade foreign nucleic acids complementary to the crRNA. This review gives an overview of CRISPR immunity to newcomers in the field and an update on CRISPR literature in archaea by comparing the functional mechanisms and abundances of the diverse CRISPR types. A bigger fraction is dedicated to the versatile and prevalent CRISPR type III systems, as tremendous progress has been made recently using archaeal models in discerning the controlled molecular mechanisms of their unique tripartite mode of action including RNA interference, DNA interference and the unique cyclic-oligoadenylate signaling that induces promiscuous RNA shredding by CARF-domain ribonucleases. The second half of the review spotlights CRISPR in archaea outlining seminal in vivo and in vitro studies in model organisms of the euryarchaeal and crenarchaeal phyla, including the application of CRISPR-Cas for genome editing and gene silencing. In the last section, a special focus is laid on members of the crenarchaeal hyperthermophilic order Sulfolobales by presenting a thorough comparative analysis about the distribution and abundance of CRISPR-Cas systems, including arrays and spacers as well as CRISPR-accessory proteins in all 53 genomes available to date. Interestingly, we find that CRISPR type III and the DNA-degrading CRISPR type I complexes co-exist in more than two thirds of these genomes. Furthermore, we identified ring nuclease candidates in all but two genomes and found that they generally co-exist with the above-mentioned CARF domain ribonucleases Csx1/Csm6. These observations, together with published literature allowed us to draft a working model of how CRISPR-Cas systems and accessory proteins cross talk to establish native CRISPR anti-virus immunity in a Sulfolobales cell.

scholarly journals Mecanismos Moleculares de Adesão e Colonização da Mucosa Gástrica pela Helicobacter pylori e suas Implicações Clínicas

2016 ◽  
Vol 29 (7-8) ◽  
pp. 476 ◽  
Author(s):  
Elisabete Coelho ◽  
Ana Magalhães ◽  
Mário Dinis-Ribeiro ◽  
Celso A. Reis
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelium ◽  
Antibiotics Resistance ◽  
Gastric Disease ◽  
Preventive Strategy

Introduction: Helicobacter pylori infection is very prevalent worldwide and is associated with the progression of the gastriccarcinogenesis cascade, being one of the main risk factors for the development of gastric carcinoma. Several factors are determinant for the infection and for the development of gastric disease, including environmental factors, host genetic factors and virulence factors of the bacteria.Material and Methods: In this review, we present an overview of the current knowledge on the determinants of the infection and on the recently described molecular mechanisms of Helicobacter pylori adhesion to the gastric mucosa, as well as its possible future therapeutic application.Results: The adhesion of Helicobacter pylori to the gastric epithelium is critical for gastric pathogenesis, allowing bacterial access to nutrients and the action of bacterial virulence factors, promoting recurrence of the infection and the progression of the gastric carcinogenesis pathway.Discussion: Eradication of Helicobacter pylori infection is the best preventive strategy available against gastric cancer, mainly if it is achieved before the development of pre-neoplastic lesions. The increase in antibiotics resistance, together with the eradication failures in some patients, has promoted the development of alternative treatments.Conclusion: The new therapeutic strategies, focused on the molecular mechanism of Helicobacter pylori adhesion, are very promising; however, future studies are needed to evaluate its in vivo efficiency and toxicity.

scholarly journals Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1936 ◽  
Author(s):  
Aide Negri ◽  
Valeria Naponelli ◽  
Federica Rizzi ◽  
Saverio Bettuzzi
Keyword(s):  
Cell Proliferation ◽  
Green Tea ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Dna Methyltransferases ◽  
Biologically Active ◽  
Special Focus ◽  
Dependent Inhibition

Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are catechins, a family of polyphenols. Among them, epigallocatechin-gallate (EGCG) is the most abundant and biologically active. EGCG is widely studied for its anti-cancer properties. However, the cellular and molecular mechanisms explaining its action have not been completely understood, yet. EGCG is effective in vivo at micromolar concentrations, suggesting that its action is mediated by interaction with specific targets that are involved in the regulation of crucial steps of cell proliferation, survival, and metastatic spread. Recently, several proteins have been identified as EGCG direct interactors. Among them, the trans-membrane receptor 67LR has been identified as a high affinity EGCG receptor. 67LR is a master regulator of many pathways affecting cell proliferation or apoptosis, also regulating cancer stem cells (CSCs) activity. EGCG was also found to be interacting directly with Pin1, TGFR-II, and metalloproteinases (MMPs) (mainly MMP2 and MMP9), which respectively regulate EGCG-dependent inhibition of NF-kB, epithelial-mesenchimal transaction (EMT) and cellular invasion. EGCG interacts with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which modulates epigenetic changes. The bulk of this novel knowledge provides information about the mechanisms of action of EGCG and may explain its onco-suppressive function. The identification of crucial signalling pathways that are related to cancer onset and progression whose master regulators interacts with EGCG may disclose intriguing pharmacological targets, and eventually lead to novel combined treatments in which EGCG acts synergistically with known drugs.

scholarly journals Genetic Mouse Models as In Vivo Tools for Cholangiocarcinoma Research

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1868 ◽  
Author(s):  
Oihane Erice ◽  
Adrian Vallejo ◽  
Mariano Ponz-Sarvise ◽  
Michael Saborowski ◽  
Arndt Vogel ◽  
...  
Keyword(s):  
Mouse Models ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
In Vivo Model ◽  
In Vivo Models ◽  
Dismal Prognosis ◽  
Genetic Mouse Models

Cholangiocarcinoma (CCA) is a genetically and histologically complex disease with a highly dismal prognosis. A deeper understanding of the underlying cellular and molecular mechanisms of human CCA will increase our current knowledge of the disease and expedite the eventual development of novel therapeutic strategies for this fatal cancer. This endeavor is effectively supported by genetic mouse models, which serve as sophisticated tools to systematically investigate CCA pathobiology and treatment response. These in vivo models feature many of the genetic alterations found in humans, recapitulate multiple hallmarks of cholangiocarcinogenesis (encompassing cell transformation, preneoplastic lesions, established tumors and metastatic disease) and provide an ideal experimental setting to study the interplay between tumor cells and the surrounding stroma. This review is intended to serve as a compendium of CCA mouse models, including traditional transgenic models but also genetically flexible approaches based on either the direct introduction of DNA into liver cells or transplantation of pre-malignant cells, and is meant as a resource for CCA researchers to aid in the selection of the most appropriate in vivo model system.

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