scholarly journals Targeted Cancer Therapy Using Compounds Activated by Light

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3237
Author(s):  
Petra Dunkel ◽  
Janez Ilaš
Keyword(s):  
Rapid Development ◽  
Targeted Cancer Therapy ◽  
Light Activation ◽  
Pharmacological Interventions ◽  
Experimental Phase ◽  
Anticancer Compounds ◽  
Selective Agents ◽  
Photoremovable Protecting Groups ◽  
Immense Potential

Cancer chemotherapy is affected by a modest selectivity and toxic side effects of pharmacological interventions. Among novel approaches to overcome this limitation and to bring to therapy more potent and selective agents is the use of light for selective activation of anticancer compounds. In this review, we focus on the anticancer applications of two light-activated approaches still in the experimental phase: photoremovable protecting groups (“photocages”) and photoswitches. We describe the structural considerations behind the development of novel compounds and the plethora of assays used to confirm whether the photochemical and pharmacological properties are meeting the stringent criteria for an efficient in vivo light-dependent activation. Despite its immense potential, light activation brings many challenges, and the complexity of the task is very demanding. Currently, we are still deeply in the phase of pharmacological tools, but the vivid research and rapid development bring the light of hope for potential clinical use.

The Synergy between CRISPR and Chemical Engineering

2019 ◽  
Vol 19 (3) ◽  
pp. 147-171
Author(s):  
Cia-Hin Lau ◽  
Chung Tin
Keyword(s):  
Viral Vectors ◽  
Chemical Engineering ◽  
Target Genes ◽  
New Technologies ◽  
Rapid Development ◽  
Genetic Circuits ◽  
Viral Packaging ◽  
Conditional Control ◽  
Logic Operations

Gene therapy and transgenic research have advanced quickly in recent years due to the development of CRISPR technology. The rapid development of CRISPR technology has been largely benefited by chemical engineering. Firstly, chemical or synthetic substance enables spatiotemporal and conditional control of Cas9 or dCas9 activities. It prevents the leaky expression of CRISPR components, as well as minimizes toxicity and off-target effects. Multi-input logic operations and complex genetic circuits can also be implemented via multiplexed and orthogonal regulation of target genes. Secondly, rational chemical modifications to the sgRNA enhance gene editing efficiency and specificity by improving sgRNA stability and binding affinity to on-target genomic loci, and hence reducing off-target mismatches and systemic immunogenicity. Chemically-modified Cas9 mRNA is also more active and less immunogenic than the native mRNA. Thirdly, nonviral vehicles can circumvent the challenges associated with viral packaging and production through the delivery of Cas9-sgRNA ribonucleoprotein complex or large Cas9 expression plasmids. Multi-functional nanovectors enhance genome editing in vivo by overcoming multiple physiological barriers, enabling ligand-targeted cellular uptake, and blood-brain barrier crossing. Chemical engineering can also facilitate viral-based delivery by improving vector internalization, allowing tissue-specific transgene expression, and preventing inactivation of the viral vectors in vivo. This review aims to discuss how chemical engineering has helped improve existing CRISPR applications and enable new technologies for biomedical research. The usefulness, advantages, and molecular action for each chemical engineering approach are also highlighted.

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

scholarly journals Characterization of the SARS-CoV-2 coronavirus X4-like accessory protein

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Nkwachukwu Oziamara Okoro ◽  
Arome Solomon Odiba
Keyword(s):  
Rapid Development ◽  
Protein A ◽  
The Novel ◽  
Quality Model ◽  
A Value ◽  
Model Protein ◽  
Novel Coronavirus ◽  
Global Threat

Abstract Background The novel coronavirus SARS-CoV-2 is currently a global threat to health and economies. Therapeutics and vaccines are in rapid development; however, none of these therapeutics are considered as absolute cure, and the potential to mutate makes it necessary to find therapeutics that target a highly conserved regions of the viral structure. Results In this study, we characterized an essential but poorly understood coronavirus accessory X4 protein, a core and stable component of the SARS-CoV family. Sequence analysis shows a conserved ~ 90% identity between the SARS-CoV-2 and previously characterized X4 protein in the database. QMEAN Z score of the model protein shows a value of around 0.5, within the acceptable range 0–1. A MolProbity score of 2.96 was obtained for the model protein and indicates a good quality model. The model has Ramachandran values of φ = − 57o and ψ = − 47o for α-helices and values of φ = − 130o and ψ = + 140o for twisted sheets. Conclusions The protein data obtained from this study provides robust information for further in vitro and in vivo experiment, targeted at devising therapeutics against the virus. Phylogenetic analysis further supports previous evidence that the SARS-CoV-2 is positioned with the SL-CoVZC45, BtRs-BetaCoV/YN2018B and the RS4231 Bat SARS-like corona viruses.

scholarly journals Zebrafish Models of Autosomal Recessive Ataxias

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 836
Author(s):  
Ana Quelle-Regaldie ◽  
Daniel Sobrido-Cameán ◽  
Antón Barreiro-Iglesias ◽  
María Jesús Sobrido ◽  
Laura Sánchez
Keyword(s):  
Animal Models ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
System Development ◽  
Rapid Development ◽  
Nervous System Development ◽  
Central Nervous System Development ◽  
Cellular Processes ◽  
Recessive Disorders

Autosomal recessive ataxias are much less well studied than autosomal dominant ataxias and there are no clearly defined systems to classify them. Autosomal recessive ataxias, which are characterized by neuronal and multisystemic features, have significant overlapping symptoms with other complex multisystemic recessive disorders. The generation of animal models of neurodegenerative disorders increases our knowledge of their cellular and molecular mechanisms and helps in the search for new therapies. Among animal models, the zebrafish, which shares 70% of its genome with humans, offer the advantages of being small in size and demonstrating rapid development, making them optimal for high throughput drug and genetic screening. Furthermore, embryo and larval transparency allows to visualize cellular processes and central nervous system development in vivo. In this review, we discuss the contributions of zebrafish models to the study of autosomal recessive ataxias characteristic phenotypes, behavior, and gene function, in addition to commenting on possible treatments found in these models. Most of the zebrafish models generated to date recapitulate the main features of recessive ataxias.

scholarly journals Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1125
Author(s):  
Raluca Nicu ◽  
Florin Ciolacu ◽  
Diana E. Ciolacu
Keyword(s):  
Rapid Development ◽  
Cellulose Nanofibrils ◽  
Functional Materials ◽  
Medical Applications ◽  
Bacterial Nanocellulose ◽  
Green Materials ◽  
Wide Range ◽  
In Vivo Cytotoxicity

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

A brief overview on role of graphene based material in therapeutic management of inflammatory response signalling cascades

2020 ◽  
Vol 21 ◽  
pp. 25-36
Author(s):  
Ruchira Das ◽  
◽  
Priyanka Sow ◽  
Sudatta Dey ◽  
Asmita Samadder ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Water Solubility ◽  
Biomedical Application ◽  
Rapid Development ◽  
Graphene Quantum Dots ◽  
Biological Response ◽  
Vital Role ◽  
Therapeutic Management ◽  
In Vivo Models

Graphene is a novel, sp2 carbon atoms bonded, two-dimensional nano-material. Due to their favorable electronic, thermal, optical, and mechanical property, graphene and its derivatives, like graphene oxide (GO) and graphene quantum dots (GQDs) are used in widespread applications. The outstanding potentials of these compounds in the field of nanoelectronics, composite materials, sensors, energy technology etc helped in the rapid development in their functionalization, modulatory effects on various systems of our body. GQDs has been suggested as a new nanomaterial with improved biocompatibility, biodegradability, water solubility and considerably low cytotoxic effects in in vivo models, and are applicable for altering immune responses based on quantum confinement and edge effect properties. The review particularly elucidates the mechanistic approach by which graphene and/ or its derivatives and/ or their nano-compound aid in therapeutic management against myriads of immunological perspectives. GQDs have unique physiochemical properties with carbon sheets showcases out-standing biological response against immunological interventions by altering the activities of t-cell lymphocytes. On the contrary GO plays a vital role in eliciting inflammatory signaling factors by controlling proinflammation and an anti-inflammatory response. Therefore, this review shall help the readers to have an overview of the biomedical application of graphene and its derivatives to design target specific drugs to regulate the immune response based prognosis andcure.

scholarly journals Tissue-informed engineering strategies for modeling human pulmonary diseases

2019 ◽  
Vol 316 (2) ◽  
pp. L303-L320 ◽  
Author(s):  
Kolene E. Bailey ◽  
Michael L. Floren ◽  
Tyler J. D’Ovidio ◽  
Steven R. Lammers ◽  
Kurt R. Stenmark ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Rapid Development ◽  
Rapid Expansion ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Management Options ◽  
Dynamic Changes ◽  
Human Pathology ◽  
Chronic Pulmonary Diseases

Chronic pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), and chronic obstructive pulmonary disease (COPD), account for staggering morbidity and mortality worldwide but have limited clinical management options available. Although great progress has been made to elucidate the cellular and molecular pathways underlying these diseases, there remains a significant disparity between basic research endeavors and clinical outcomes. This discrepancy is due in part to the failure of many current disease models to recapitulate the dynamic changes that occur during pathogenesis in vivo. As a result, pulmonary medicine has recently experienced a rapid expansion in the application of engineering principles to characterize changes in human tissues in vivo and model the resulting pathogenic alterations in vitro. We envision that engineering strategies using precision biomaterials and advanced biomanufacturing will revolutionize current approaches to disease modeling and accelerate the development and validation of personalized therapies. This review highlights how advances in lung tissue characterization reveal dynamic changes in the structure, mechanics, and composition of the extracellular matrix in chronic pulmonary diseases and how this information paves the way for tissue-informed engineering of more organotypic models of human pathology. Current translational challenges are discussed as well as opportunities to overcome these barriers with precision biomaterial design and advanced biomanufacturing techniques that embody the principles of personalized medicine to facilitate the rapid development of novel therapeutics for this devastating group of chronic diseases.

The Infection of the ventriculus of the adult honeybee by Nosema apis (Zander)

Parasitology ◽  
1955 ◽  
Vol 45 (1-2) ◽  
pp. 86-94 ◽  
Author(s):  
L. Bailey
Keyword(s):  
Calcium Phosphate ◽  
Central Region ◽  
Polar Filament ◽  
Rapid Development ◽  
Nosema Apis ◽  
Anaerobic Conditions ◽  
Free Living ◽  
Initial Infection ◽  
High Level

1. Spores of Nosema apis nearly all germinate within 30 min. after entering the ventriculus of the honeybee.2. The cause of germination in vivo remains unknown, but is probably not a change of osmotic pressure or pH and is probably not due to anaerobic conditions or an enzyme. The agent causing germination is probably unstable and is destroyed when removed from the bee.3. The anterior end of the ventriculus receives an initial heavy infection and the circumstantial evidence which this provides supports the theory that a free living ‘planont’ stage does not exist but that the parasite is injected directly into the host cell from the spore via the hollow polar filament.4. The central region of the ventriculus which contains many granules of calcium phosphate receives the lowest initial infection. It is considered possible that the granules inhibit the initial rapid development of the parasite by maintaining an unfavourably high level of pH until they are eventually dissolved by the slowly developing organism.

scholarly journals Non-invasive imaging of the coronary arteries

2018 ◽  
Vol 40 (29) ◽  
pp. 2444-2454 ◽  
Author(s):  
Philip D Adamson ◽  
David E Newby
Keyword(s):  
Coronary Arteries ◽  
Randomized Clinical Trials ◽  
Rapid Development ◽  
Current Status ◽  
Future Research ◽  
Research Perspective ◽  
Non Invasive ◽  
Positron Emission ◽  
Prognostic Stratification

Abstract Non-invasive imaging of the coronary arteries is an enterprise in rapid development. From the research perspective, there is great demand for in vivo techniques that can reliably identify features of high-risk plaque that may offer insight into pathophysiological processes and act as surrogate indicators of response to therapeutic intervention. Meanwhile, there is clear clinical need for greater accuracy in diagnosis and prognostic stratification. Fortunately, ongoing technological improvements and emerging data from randomized clinical trials are helping make these elusive goals a reality. This review provides an update on the current status of non-invasive coronary imaging with computed tomography, magnetic resonance, and positron emission tomography with a focus on current clinical applications and future research directions.

scholarly journals Current and Future Advancements of Raman Spectroscopy Techniques in Cancer Nanomedicine

2021 ◽  
Vol 22 (23) ◽  
pp. 13141
Author(s):  
Elisabetta Canetta
Keyword(s):  
Raman Spectroscopy ◽  
Imaging Techniques ◽  
Rapid Development ◽  
Surface Enhanced Raman Spectroscopy ◽  
Cancer Diagnostics ◽  
Raman Signal ◽  
Therapeutic Effects ◽  
Cancer Nanomedicine

Raman scattering is one of the most used spectroscopy and imaging techniques in cancer nanomedicine due to its high spatial resolution, high chemical specificity, and multiplexity modalities. The flexibility of Raman techniques has led, in the past few years, to the rapid development of Raman spectroscopy and imaging for nanodiagnostics, nanotherapy, and nanotheranostics. This review focuses on the applications of spontaneous Raman spectroscopy and bioimaging to cancer nanotheranostics and their coupling to a variety of diagnostic/therapy methods to create nanoparticle-free theranostic systems for cancer diagnostics and therapy. Recent implementations of confocal Raman spectroscopy that led to the development of platforms for monitoring the therapeutic effects of anticancer drugs in vitro and in vivo are also reviewed. Another Raman technique that is largely employed in cancer nanomedicine, due to its ability to enhance the Raman signal, is surface-enhanced Raman spectroscopy (SERS). This review also explores the applications of the different types of SERS, such as SERRS and SORS, to cancer diagnosis through SERS nanoprobes and the detection of small-size biomarkers, such as exosomes. SERS cancer immunotherapy and immuno-SERS (iSERS) microscopy are reviewed.

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