Modeling and Analysis of a Soft Endoluminal Inchworm Robot Propelled by a Rotating Magnetic Dipole Field

2021 ◽  
pp. 1-13
Author(s):  
Jake A. Steiner ◽  
Lan N. Pham ◽  
Jake J. Abbott ◽  
Kam K. Leang
Keyword(s):  
Human Body ◽  
Ex Vivo ◽  
Circulatory System ◽  
The Body ◽  
Modeling And Analysis ◽  
Gait Characteristics ◽  
Physical Experiments ◽  
Design Variables ◽  
Magnetic Dipole Field

Abstract In clinical practice, therapeutic and diagnostic endoluminal procedures of the human body often use a scope, catheter, or passive pill-shaped camera. Unfortunately, such procedures in the circulatory system and gastrointestinal tract are often uncomfortable, invasive, and require the patient to be sedated. With current methods, regions of the body are often inaccessible to the clinician. Herein, a magnetically-actuated soft endoluminal inchworm robot that may extend clinicians' ability to reach further into the human body and practice new procedures is described, modeled, and analyzed. A detailed locomotion model is proposed that takes into account the elastic deformation of the robot and its interactions with the environment. The model is validated with in vitro and ex vivo physical experiments and is shown to capture the robot's gait characteristics through a lumen. Utilizing dimensional analysis, the effects of the mechanical properties and design variables on the robot's motion are investigated further to advance the understanding of this endoluminal robot concept.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

scholarly journals Extracellular vesicles engineered with valency-controlled DNA nanostructures deliver CRISPR/Cas9 system for gene therapy

2020 ◽  
Vol 48 (16) ◽  
pp. 8870-8882 ◽  
Author(s):  
Jialang Zhuang ◽  
Jizhou Tan ◽  
Chenglin Wu ◽  
Jie Zhang ◽  
Ting Liu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Ex Vivo ◽  
Primary Liver Cancer ◽  
The Body ◽  
Dna Aptamer ◽  
Great Promise ◽  
Tumor Growth Inhibition ◽  
Specific Cell ◽  
Dna Nanostructures

Abstract Extracellular vesicles (EVs) hold great promise for transporting CRISPR–Cas9 RNA-guided endonucleases (RNP) throughout the body. However, the cell-selective delivery of EVs is still a challenge. Here, we designed valency-controlled tetrahedral DNA nanostructures (TDNs) conjugated with DNA aptamer, and loaded the valency-controlled TDNs on EV surface via cholesterol anchoring for specific cell targeting. The targeting efficacy of different ratios of aptamer/cholesterol from 1:3 to 3:1 in TDNs on decorating EVs was investigated. TDNs with one aptamer and three cholesterol anchors (TDN1) efficiently facilitated the tumor-specific accumulation of the EVs in cultured HepG2 cells and human primary liver cancer-derived organoids, as well as xenograft tumor models. The intracellular delivery of RNP by TDN1-EVs successfully realized its subsequent genome editing, leading to the downregulation of GFP or WNT10B in specific cells. This system was ultimately applied to reduce the protein expression of WNT10B, which presented remarkable tumor growth inhibition in vitro, ex vivo and in vivo, and could be extended to other therapeutic targets. The present study provides a platform for the directional display of aptamer on surface labeling and the EVs-based Cas9 delivery, which provides a meaningful idea for future cell-selective gene editing.

scholarly journals Zinc-containing bioactive glasses for bone regeneration, dental and orthopedic applications

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Preethi Balasubramanian ◽  
Leonie A. Strobel ◽  
Ulrich Kneser ◽  
Aldo R. Boccaccini
Keyword(s):  
Mechanical Properties ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Human Body ◽  
Relevant Literature ◽  
The Body ◽  
Biological Behavior ◽  
Bioactive Glasses ◽  
Immune System Cell

AbstractZinc is a vital and beneficial trace element found in the human body. Though found in small proportions, zinc performs a variety of functions in relation to the immune system, cell division, fertility and the body growth and maintenance. In particular, zinc is proven to be a necessary element for the formation, mineralization, development and maintenance of healthy bones. Considering this attractive attributes of zinc, recent research has widely focused on using zinc along with silicate-based bioactive glasses for bone tissue engineering applications. This paper reviews relevant literature discussing the significance of zinc in the human body, along with its ability to enhance antibacterial effects, bioactivity and distinct physical, structural and mechanical properties of bioactive glasses. In this context, even if the present analysis is not meant to be exhaustive and only representative studies are discussed, literature results confirm that it is essential to understand the properties of zinc-containing bioactive glasses with respect to their in vitro biological behavior, possible cytotoxic effects and degradation characteristics to be able to effectively apply these glasses in bone regeneration strategies. Topics attracting increasing research efforts in this field are elaborated in detail in this review, including a summary of the structural, physical, biological and mechanical properties of zinc-containing bioactive glasses. This paper also presents an overview of the various applications in which zinc-containing bioactive glasses are considered for use as bone tissue scaffolds, bone filling granules, bioactive coatings and bone cements, and advances and remaining challenges are highlighted.

Biomechanical Analysis on the Foot under Normal and Abnormal Gait for Orthotics Design

2007 ◽  
Vol 353-358 ◽  
pp. 2179-2182 ◽  
Author(s):  
Jae Ok Lee ◽  
Young Shin Lee ◽  
Se Hoon Lee ◽  
Young Jin Choi ◽  
Soung Ha Park
Keyword(s):  
Gait Analysis ◽  
Human Body ◽  
Center Of Pressure ◽  
Reaction Force ◽  
The Body ◽  
Biomechanical Analysis ◽  
Gait Characteristics ◽  
Abnormal Gait ◽  
Experimental Apparatus ◽  
Analysis System

The foot plays an important role in supporting the body and keeping body balance. An abnormal walking habit breaks the balance of the human body as well as the function of the foot. The foot orthotics which is designed to consider biomechanics effectively distributes the load of the human body on the sole of the foot. In this paper, gait analysis is performed for subjects wearing the orthotics. In this study, three male subjects were selected. The experimental apparatus consists of a plantar pressure analysis system and digital EMG system. The gait characteristics are simulated by ADAMS/LifeMOD. The COP (Center of Pressure), EMG and ground reaction force were investigated. As a result of gait analysis, the path of COP was improved and muscle activities were decreased with orthotics on the abnormal walking subjects.

scholarly journals [68Ga]ABY-028: an albumin-binding domain (ABD) protein-based imaging tracer for positron emission tomography (PET) studies of altered vascular permeability and predictions of albumin-drug conjugate transport

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Emma Jussing ◽  
Li Lu ◽  
Jonas Grafström ◽  
Tetyana Tegnebratt ◽  
Fabian Arnberg ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Vascular Permeability ◽  
Ex Vivo ◽  
Circulatory System ◽  
Binding Domain ◽  
The Body ◽  
Emission Tomography ◽  
Albumin Binding ◽  
Positron Emission

Abstract Background Albumin is commonly used as a carrier platform for drugs to extend their circulatory half-lives and influence their uptake into tissues that have altered permeability to the plasma protein. The albumin-binding domain (ABD) protein, which binds in vivo to serum albumin with high affinity, has proven to be a versatile scaffold for engineering biopharmaceuticals with a range of binding capabilities. In this study, the ABD protein equipped with a mal-DOTA chelator (denoted ABY-028) was radiolabeled with gallium-68 (68Ga). This novel radiotracer was then used together with positron emission tomography (PET) imaging to examine variations in the uptake of the ABD-albumin conjugate with variations in endothelial permeability. Results ABY-028, produced by peptide synthesis in excellent purity and stored at − 20 °C, was stable for 24 months (end of study). [68Ga]ABY-028 could be obtained with labeling yields of > 80% and approximately 95% radiochemical purity. [68Ga]ABY-028 distributed in vivo with the plasma pool, with highest radioactivity in the heart ventricles and major vessels of the body, a gradual transport over time from the circulatory system into tissues and elimination via the kidneys. Early [68Ga]ABY-028 uptake differed in xenografts with different vascular properties: mean standard uptake values (SUVmean) were initially 5 times larger in FaDu than in A431 xenografts, but the difference decreased to 3 after 1 h. Cutaneously administered, vasoactive nitroglycerin increased radioactivity in the A431 xenografts. Heterogeneity in the levels and rates of increases of radioactivity uptake was observed in sub-regions of individual MMTV-PyMT mammary tumors and in FaDu xenografts. Higher uptake early after tracer administration could be observed in lower metabolic regions. Fluctuations in the increased permeability for the tracer across the blood-brain-barrier (BBB) direct after experimentally induced stroke were monitored by PET and the increased uptake was confirmed by ex vivo phosphorimaging. Conclusions [68Ga]ABY-028 is a promising new tracer for visualization of changes in albumin uptake due to disease- and pharmacologically altered vascular permeability and their potential effects on the passive uptake of targeting therapeutics based on the ABD protein technology.

scholarly journals Platelet generation from circulating megakaryocytes is triggered in the lung vasculature

2021 ◽  
Author(s):  
Xiaojuan Zhao ◽  
Dominic Alibhai ◽  
Tony G. Walsh ◽  
Nathalie Tarassova ◽  
Semra Z. Birol ◽  
...  
Keyword(s):  
Blood Cells ◽  
Ex Vivo ◽  
Critical Role ◽  
The Body ◽  
Mouse Lung ◽  
Generation Process ◽  
Large Size ◽  
Large Numbers ◽  
Microfluidic Chamber

Platelets, small hemostatic blood cells, are derived from megakaryocytes, although the generation process is not clear. Only small numbers of platelets have been produced in systems outside the body, where bone marrow and lung are proposed as sites of platelet generation. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates very large numbers of platelets, up to 3,000 per megakaryocyte. Despite their large size, megakaryocytes were able repeatedly to passage through the lung vasculature, leading to enucleation and fragmentation to generate platelets intravascularly. Using the ex vivo lung and a novel in vitro microfluidic chamber we determined the contributions of oxygenation, ventilation and endothelial cell health to platelet generation, and showed a critical role for the actin regulator TPM4.

Embryonic development—the first few weeks

2013 ◽  
Author(s):  
Martin E. Atkinson
Keyword(s):  
Embryonic Development ◽  
Human Body ◽  
Circulatory System ◽  
Building Blocks ◽  
The Body ◽  
The Other ◽  
Developmental Anatomy ◽  
Fetal Period ◽  
Embryonic Period ◽  
Degree Of Overlap

Embryology is a fascinating subject and is the foundation of the development, growth, and maturation of all the cells, organs, and tissues of the body. Strictly, embryology is the study of the early processes of development beginning at fertilization and following the processes that turn a single cell into a multicellular organism. It is all about generation of the building blocks required to make a human body. Developmental anatomy is the study of how these building blocks are turned into specific cells, tissues, and organs as well as the general growth of the body. As you will soon appreciate in the following paragraphs, all organs and systems do not develop at the same rate so there is a degree of overlap between embryology and developmental anatomy. For example, the heart and circulatory system must develop and be functioning very early in development to ensure adequate supplies of nutrients to the developing fetal tissues. Teeth, on the other hand, are not going to be used until about six months after birth at the earliest; while the heart is already beating away, each developing tooth is merely a tiny group of cells bearing little resemblance to a fully formed tooth. Human gestation is considered to take nine months; more accurately, it usually lasts for 38 to 39 weeks from fertilization to birth. Clinically, it is divided into three trimesters of three months each. In this chapter, we will focus on events in the first few weeks. During the first two and a half weeks after fertilization, the very basic building blocks are formed from the single fertilized cell; this is the pre-embryonic period. The embryonic period covers the next five and half weeks during which these basic building blocks develop into the cells, tissues, and organs. As already indicated, some of these may be in a very rudimentary state at the end of the embryonic period. The remaining 30 or so weeks is the fetal period when the tissues and organs of the body grow and develop and the fetus grows considerably. We are not fully mature organisms at birth and have another 20 years a-growing.

Body-on-a chip: Using microfluidic systems to predict human responses to drugs

2010 ◽  
Vol 82 (8) ◽  
pp. 1635-1645 ◽  
Author(s):  
Michael L. Shuler ◽  
Mandy B. Esch
Keyword(s):  
Cell Culture ◽  
Human Body ◽  
Mammalian Cells ◽  
Circulatory System ◽  
Systemic Circulation ◽  
Multidrug Resistant ◽  
Toxicological Studies ◽  
In Vitro Systems ◽  
Barrier Tissues

Using an in vitro platform technology that combines microfabricated devices with cell culture, we seek to understand the response of the human body to pharmaceuticals and combinations of pharmaceuticals. Computer models of the human body guide the design of in vitro systems we call micro cell culture analogs (μCCAs) or “body-on-a-chip” devices. A μCCA device is a physical representation of a physiologically based pharmacokinetic (PBPK) model and contains mammalian cells cultured in interconnected microchambers to represent key organs linked through a circulatory system. μCCAs can provide inexpensive means for realistic, accurate, and rapid-throughput toxicological studies that do not require experimenting with animals and reveal toxic effects that can result from interactions between organs. As the natural length scale in biological systems is on the order of 10–100 μm, operating on the microscale allows us to mimic physiological relationships more accurately. We summarize proof-of-concept experiments using mixtures of drugs to treat multidrug-resistant (MDR) cancer and colon cancer. We discuss the extension of the μCCA concept to systems that connect barrier tissues with systemic circulation. Examples with models of the gastro-intestinal (GI) tract are provided.

scholarly journals Iodine-124 PET quantification of organ-specific delivery and expression of NIS-encoding RNA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthias Miederer ◽  
Stefanie Pektor ◽  
Isabelle Miederer ◽  
Nicole Bausbacher ◽  
Isabell Sofia Keil ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ex Vivo ◽  
Small Animal ◽  
Protein Translation ◽  
The Body ◽  
Small Animal Pet ◽  
Animal Pet ◽  
Organ Specific

Abstract Background RNA-based vaccination strategies tailoring immune response to specific reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. Here, we have investigated whether small animal PET/MRI can be employed to image the biodistribution of RNA-encoded protein. For this purpose, a reporter RNA coding for the sodium-iodide-symporter (NIS) was in vitro transcribed in cell lines and evaluated for expression. RNA-lipoplex nanoparticles were then assembled by complexing RNA with liposomes at different charge ratios, and functional NIS protein translation was imaged and quantified in vivo and ex vivo by Iodine-124 PET upon intravenous administration in mice. Results NIS expression was detected on the membrane of two cell lines as early as 6 h after transfection and gradually decreased over 48 h. In vivo and ex vivo PET/MRI of anionic spleen-targeting or cationic lung-targeting NIS-RNA lipoplexes revealed a visually detectable rapid increase of Iodine-124 uptake in the spleen or lung compared to control-RNA-lipoplexes, respectively, with minimal background in other organs except from thyroid, stomach and salivary gland. Conclusions The strong organ selectivity and high target-to-background acquisition of NIS-RNA lipoplexes indicate the feasibility of small animal PET/MRI to quantify organ-specific delivery of RNA.

scholarly journals The fate of methylmercury through the formation of bismethylmercury sulfide as an intermediate in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumi Abiko ◽  
Yusuke Katayama ◽  
Wenyang Zhao ◽  
Sawako Horai ◽  
Kenji Sakurai ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Intraperitoneal Administration ◽  
Distal Colon ◽  
The Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Dependent Manner ◽  
Free System ◽  
A Cell

AbstractA previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body. In the present study, we explored the transformation of MeHg to (MeHg)2S in the gut and the subsequent fate of (MeHg)2S in vitro and in vivo. An ex vivo experiment suggested the possibility of the extracellular transformation of MeHg to (MeHg)2S in the distal colon, and accordingly, the MeHg sulfur adduct was detected in the intestinal contents and feces of mice administered MeHg, suggesting that (MeHg)2S is formed through reactions between MeHg and RSS in the gut. In a cell-free system, we found that (MeHg)2S undergoes degradation in a time-dependent manner, resulting in the formation of mercury sulfide and dimethylmercury (DMeHg), as determined by X-ray diffraction and gas chromatography/mass spectrometry, respectively. We also identified DMeHg in the expiration after the intraperitoneal administration of (MeHg)2S to mice. Thus, our present study identified a new fate of MeHg through (MeHg)2S as an intermediate, which leads to conversion of volatile DMeHg in the body.

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