Enzyme-Instructed Self-assembly in Biological Milieu for Theranostics Purpose

2019 ◽  
Vol 26 (8) ◽  
pp. 1351-1365 ◽  
Author(s):  
Zhentao Huang ◽  
Qingxin Yao ◽  
Simin Wei ◽  
Jiali Chen ◽  
Yuan Gao
Keyword(s):  
Small Molecules ◽  
Precision Medicine ◽  
Self Assembly ◽  
Public Healthcare ◽  
Enzymatic Conversion ◽  
Vaccine Adjuvants ◽  
New Paradigm ◽  
Cancer Treatments ◽  
The Past ◽  
Biological Milieu

Precision medicine is in an urgent need for public healthcare. Among the past several decades, the flourishing development in nanotechnology significantly advances the realization of precision nanomedicine. Comparing to well-documented nanoparticlebased strategy, in this review, we focus on the strategy using enzyme instructed selfassembly (EISA) in biological milieu for theranostics purpose. In principle, the design of small molecules for EISA requires two aspects: (1) the substrate of enzyme of interest; and (2) self-assembly potency after enzymatic conversion. This strategy has shown its irreplaceable advantages in nanomedicne, specifically for cancer treatments and Vaccine Adjuvants. Interestingly, all the reported examples rely on only one kind of enzymehydrolase. Therefore, we envision that the application of EISA strategy just begins and will lead to a new paradigm in nanomedicine.

Video real-time imaging of artificial membranes during freeze-drying by cryo-electron microscopy

1988 ◽  
Vol 46 ◽  
pp. 16-17
Author(s):  
Alan S. Rudolph ◽  
Ronald R. Price
Keyword(s):  
Real Time ◽  
Self Assembly ◽  
Freeze Drying ◽  
Video Capture ◽  
Drying Process ◽  
Artificial Membranes ◽  
The Past ◽  
Cryo Electron Microscopy ◽  
Spherical Structures ◽  
Capture Techniques

We have employed cryoelectron microscopy to visualize events that occur during the freeze-drying of artificial membranes by employing real time video capture techniques. Artificial membranes or liposomes which are spherical structures within internal aqueous space are stabilized by water which provides the driving force for spontaneous self-assembly of these structures. Previous assays of damage to these structures which are induced by freeze drying reveal that the two principal deleterious events that occur are 1) fusion of liposomes and 2) leakage of contents trapped within the liposome [1]. In the past the only way to access these events was to examine the liposomes following the dehydration event. This technique allows the event to be monitored in real time as the liposomes destabilize and as water is sublimed at cryo temperatures in the vacuum of the microscope. The method by which liposomes are compromised by freeze-drying are largely unknown. This technique has shown that cryo-protectants such as glycerol and carbohydrates are able to maintain liposomal structure throughout the drying process.

On the formation of a New Paradigm of fiscal Policy

2013 ◽  
pp. 152-158 ◽  
Author(s):  
V. Senchagov
Keyword(s):  
Public Finance ◽  
Fiscal Policy ◽  
Financial Crisis ◽  
Global Financial Crisis ◽  
Domestic Demand ◽  
Real Economy ◽  
New Paradigm ◽  
Monetary Aggregate ◽  
The Past ◽  
The Global Financial Crisis

Due to Russia’s exit from the global financial crisis, the fiscal policy of withdrawing windfall spending has exhausted its potential. It is important to refocus public finance to the real economy and the expansion of domestic demand. For this goal there is sufficient, but not realized financial potential. The increase in fiscal spending in these areas is unlikely to lead to higher inflation, given its actual trend in the past decade relative to M2 monetary aggregate, but will directly affect the investment component of many underdeveloped sectors, as well as the volume of domestic production and consumer demand.

Periodontopathogens: a new view. Systematic review. Part 2

2020 ◽  
Vol 20 (2) ◽  
pp. 160-167
Author(s):  
E. S. Slazhneva ◽  
E. A. Tikhomirova ◽  
V. G. Atrushkevich
Keyword(s):  
Systematic Review ◽  
Periodontal Disease ◽  
Pathogenic Bacteria ◽  
Periodontal Diseases ◽  
Oral Microbiome ◽  
Controlled Trials ◽  
New Paradigm ◽  
Microbial Composition ◽  
Randomized Controlled ◽  
The Past

Relevance. The modern view of periodontitis as a dysbiotic disease that occurs as a result of changes in the microbial composition of the subgingival region is considered in a systematic review.Purpose. To study a new paradigm of development of generalized periodontitis.Materials and methods. Randomized controlled trials (RCTS) were selected for the study, including cluster RCTS, controlled (non-randomized) microbiological and clinical studies of the oral microbiome in adult patients with generalized periodontitis over the past 10 years.Results. The transition from a symbiotic microflora to a dysbiotic pathogenic community triggers the host's inflammatory response, which contributes to the development of periodontal diseases. Modern ideas about periodontal pathogenic bacteria dictate new requirements for the treatment of periodontal diseases. The second part of the review examines the microbial profiles of periodontal disease in various nosological forms, the mechanisms of the immune response and approaches to the treatment of periodontal disease from the perspective of biofilm infection.Conclusions. As follows from modern literature periodontitis is to a certain extent caused by the transition from a harmonious symbiotic bacterial community to a dysbiotic one. Recent scientific studies have shown that not single microorganism is not able to cause disease but the microbial community as a whole leads to the development of pathology.

Computational and Experimental Binding Mechanism of DNA-drug Interactions

2019 ◽  
Vol 24 (32) ◽  
pp. 3739-3757 ◽  
Author(s):  
Chandrabose Selvaraj ◽  
Sanjeev K. Singh
Keyword(s):  
Small Molecules ◽  
Self Assembly ◽  
Genetic Material ◽  
Dna Interaction ◽  
Significant Feature ◽  
Drug Molecules ◽  
Potential Applications ◽  
Novel Drug ◽  
Groove Binders ◽  
Molecular Docking And Dynamics

Nucleic acid is the key unit and a predominant genetic material for interpreting the fundamental basis of genetic information in an organism and now it is used for the evolution of a novel group of therapeutics. To identify the potential impact on the biological science, it receives high recognition in therapeutic applications. Due to its selective recognition of molecular targets and pathways, DNA significantly imparts tremendous specificity of action. Examining the properties of DNA holds numerous advantages in assembly, interconnects, computational elements, along with potential applications of DNA self-assembly and scaffolding include nanoelectronics, biosensors, and programmable/autonomous molecular machines. The interaction of low molecular weight, small molecules with DNA is a significant feature in pharmacology. Based on the mode of binding mechanisms, small molecules are categorized as intercalators and groove binders having a significant role in target-based drug development. The understanding mechanism of drug-DNA interaction plays an important role in the development of novel drug molecules with more effective and lesser side effects. This article attempts to outline those interactions of drug-DNA with both experimental and computational advances, including ultraviolet (UV) -visible spectroscopy, fluorescent spectroscopy, circular dichroism, nuclear magnetic resonance (NMR), molecular docking and dynamics, and quantum mechanical applications.

Current Studies of Aspirin as an Anticancer Agent and Strategies to Strengthen its Therapeutic Application in Cancer

2020 ◽  
Vol 26 ◽  
Author(s):  
Phuong H.L. Tran ◽  
Beom-Jin Lee ◽  
Thao T.D. Tran
Keyword(s):  
Anticancer Agent ◽  
Mechanisms Of Action ◽  
Aspirin Therapy ◽  
Therapeutic Application ◽  
Cancer Treatments ◽  
Anticancer Properties ◽  
Cancer Management ◽  
Risk Of Bleeding ◽  
The Past ◽  
Inflammatory Drugs

: Aspirin has emerged as a promising intervention in cancer in the past decade. However, there are existing controversies regarding the anticancer properties of aspirin as its mechanism of action has not been clearly defined. In addition, the risk of bleeding in the gastrointestinal tract from aspirin is another consideration that requires medical and pharmaceutical scientists to work together to develop more potent and safe aspirin therapy in cancer. This review presents the most recent studies of aspirin with regard to its role in cancer prevention and treatment demonstrated by highlighted clinical trials, mechanisms of action as well as approaches to develop aspirin therapy best beneficial to cancer patients. Hence, this review provides readers with an overview of aspirin research in cancer that covers not only the unique features of aspirin, which differentiates aspirin from other non-steroidal anti-inflammatory drugs (NSAIDs), but also strategies that can be used in the development of drug delivery systems carrying aspirin for cancer management. These studies convey optimistic messages on continuing efforts of scientist on the way of developing an effective therapy for even patients with a low response to current cancer treatments.

scholarly journals Alternative approaches to target Myc for cancer treatment

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chen Wang ◽  
Jiawei Zhang ◽  
Jie Yin ◽  
Yichao Gan ◽  
Senlin Xu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Small Molecules ◽  
Drug Target ◽  
The Past ◽  
Physiological Processes ◽  
Alternative Approaches ◽  
Global Transcriptome ◽  
Factor C ◽  
Signaling Modules ◽  
Druggable Targets

AbstractThe Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL, which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc, respectively. Myc protein orchestrates diverse physiological processes, including cell proliferation, differentiation, survival, and apoptosis. Myc modulates about 15% of the global transcriptome, and its deregulation rewires the cellular signaling modules inside tumor cells, thereby acquiring selective advantages. The deregulation of Myc occurs in >70% of human cancers, and is related to poor prognosis; hence, hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades. Nevertheless, no specific drug is currently available to directly target Myc, mainly because of its “undruggable” properties: lack of enzymatic pocket for conventional small molecules to bind; inaccessibility for antibody due to the predominant nucleus localization of Myc. Although the topic of targeting Myc has actively been reviewed in the past decades, exciting new progresses in this field keep emerging. In this review, after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer, we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.

scholarly journals The emerging technology of biohybrid micro-robots: a review

2021 ◽  
Author(s):  
Zening Lin ◽  
Tao Jiang ◽  
Jianzhong Shang
Keyword(s):  
Self Assembly ◽  
Degrees Of Freedom ◽  
High Energy ◽  
Living Cells ◽  
Multiple Degrees Of Freedom ◽  
The Past ◽  
Great Prevalence ◽  
Performance Decline ◽  
High Energy Efficiency ◽  
Living Tissues

Abstract In the past few decades, robotics research has witnessed an increasingly high interest in miniaturized, intelligent, and integrated robots. The imperative component of a robot is the actuator that determines its performance. Although traditional rigid drives such as motors and gas engines have shown great prevalence in most macroscale circumstances, the reduction of these drives to the millimeter or even lower scale results in a significant increase in manufacturing difficulty accompanied by a remarkable performance decline. Biohybrid robots driven by living cells can be a potential solution to overcome these drawbacks by benefiting from the intrinsic microscale self-assembly of living tissues and high energy efficiency, which, among other unprecedented properties, also feature flexibility, self-repair, and even multiple degrees of freedom. This paper systematically reviews the development of biohybrid robots. First, the development of biological flexible drivers is introduced while emphasizing on their advantages over traditional drivers. Second, up-to-date works regarding biohybrid robots are reviewed in detail from three aspects: biological driving sources, actuator materials, and structures with associated control methodologies. Finally, the potential future applications and major challenges of biohybrid robots are explored. Graphic abstract

scholarly journals SpheroidPicker for automated 3D cell culture manipulation using deep learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Istvan Grexa ◽  
Akos Diosdi ◽  
Maria Harmati ◽  
Andras Kriston ◽  
Nikita Moshkov ◽  
...  
Keyword(s):  
Cell Culture ◽  
Precision Medicine ◽  
High Throughput Screening ◽  
Standard Sample ◽  
Ex Vivo ◽  
Low Cost ◽  
3D Cell Culture ◽  
Syringe Pump ◽  
Experimental Conditions ◽  
The Past

AbstractRecent statistics report that more than 3.7 million new cases of cancer occur in Europe yearly, and the disease accounts for approximately 20% of all deaths. High-throughput screening of cancer cell cultures has dominated the search for novel, effective anticancer therapies in the past decades. Recently, functional assays with patient-derived ex vivo 3D cell culture have gained importance for drug discovery and precision medicine. We recently evaluated the major advancements and needs for the 3D cell culture screening, and concluded that strictly standardized and robust sample preparation is the most desired development. Here we propose an artificial intelligence-guided low-cost 3D cell culture delivery system. It consists of a light microscope, a micromanipulator, a syringe pump, and a controller computer. The system performs morphology-based feature analysis on spheroids and can select uniform sized or shaped spheroids to transfer them between various sample holders. It can select the samples from standard sample holders, including Petri dishes and microwell plates, and then transfer them to a variety of holders up to 384 well plates. The device performs reliable semi- and fully automated spheroid transfer. This results in highly controlled experimental conditions and eliminates non-trivial side effects of sample variability that is a key aspect towards next-generation precision medicine.

Shock or Design: What Drives Fiscal De/Centralization? A Comparative Analysis of Twenty-Nine OECD Countries, 1995–2017

2020 ◽  
Vol 51 (1) ◽  
pp. 1-26
Author(s):  
Tobias Arnold ◽  
Sean Mueller ◽  
Adrian Vatter
Keyword(s):  
Crisis Management ◽  
Great Recession ◽  
Political System ◽  
Multidimensional Approach ◽  
New Paradigm ◽  
The Great Recession ◽  
The Past ◽  
Fiscal Centralization ◽  
The Impact ◽  
Active Policy

Abstract Over the past decades, decentralization has become the new paradigm in how states should organize power territorially. Carefully planned institutional re-designs are the most visible expression thereof. Yet the Great Recession of 2007–2009 has pushed governments into the opposite direction, i.e., towards centralization, to better weather the fiscal drought. Given these contradictory developments, this article compares the effects of twenty-three separate state reforms with the impact of the Great Recession on fiscal centralization in twenty-nine countries over more than two decades. In the main, our analyses attribute a larger effect to design, i.e., pro-active policy making through reforms, than reactive crisis management after a great shock. However, this difference is only apparent once we consider a state’s institutional structure, that is whether a political system is unitary or federal. Our findings thus highlight the need for a multidimensional approach to better understand the drivers of fiscal de/centralization.

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