ABSTRACT
Every year, almost 4 million patients received medical care for knee osteoarthritis. Osteoarthritis involves progressive deterioration or degenerative changes in the cartilage, leading to inflammation and pain as the bones and ligaments are affected. To enhance treatment and surgical outcomes, various studies analyzing the biomechanics of the human skeletal system by fabricating simulated bones, particularly those reflecting the characteristics of patients with knee osteoarthritis, are underway. In this study, we fabricated replicated bones that mirror the bone characteristics of patients with knee osteoarthritis and developed a skeletal model that mimics the actual movement of the knee. To create patient-specific replicated bones, models were extracted from computerized tomography (CT) scans of knee osteoarthritis patients. Utilizing 3D printing technology, we replicated the femur and tibia, which bear the weight of the body and support movement, and manufactured cartilage capable of absorbing and dispersing the impact of knee joint loads using flexible polymers. Furthermore, to implement knee movement in the skeletal model, we developed artificial muscles based on shape memory alloys (SMAs) and used them to mimic the rolling, sliding, and spinning motions of knee flexion. The knee movement was investigated by changing the SMA spring's position, the number of coils, and the applied voltage. Additionally, we developed a knee-joint-mimicking system to analyze the movement of the femur. The proposed artificial-skeletal-model-based knee-joint-mimicking system appears to be applicable for analyzing skeletal models of knee patients and developing surgical simulation equipment for artificial joint replacement surgery.
ABSTRACT
A Dielectric Elastomer Actuator (DEA) consists of electrodes with a dielectric layer between them. By controlling the design of the electrodes, voltage, and frequency, the operating range and speed of the DEA can be adjusted. These DEAs find applications in biomimetic robots, artificial muscles, and similar fields. When voltage is applied to the DEA, the dielectric layer undergoes compression and expansion due to electrostatic forces, which can lead to electrical breakdown. This phenomenon is closely related to the performance and lifespan of the DEA. To enhance stability and improve dielectric properties, a DEA Reservoir layer is introduced. Here, stability refers to the ability of the DEA to perform its functions even as the applied voltage increases. The Reservoir layer delays electrical breakdown and enhances stability due to its enhanced thickness. The proposed DEA in this paper is composed of a Reservoir layer and electrode layer. The Reservoir layer is placed between the electrode layers and is independently configured, not subjected to applied voltage like the electrode layers. The performance of the DEA was evaluated by varying the number of polymer layers in the Reservoir and electrode designs. Introducing the Reservoir layer improved the dielectric properties of the DEA and delayed electrical breakdown. Increasing the dielectric constant through the DEA Reservoir can enhance output characteristics in response to electrical signals. This approach can be utilized in various applications in wearable devices, artificial muscles, and other fields.
ABSTRACT
BACKGROUND/AIM: Macropinocytosis is a non-selective form of endocytosis that facilitates the uptake of extracellular substances, such as nutrients and macromolecules, into the cells. In KRAS-driven cancers, including pancreatic ductal adenocarcinoma, macropinocytosis and subsequent lysosomal utilization are known to be enhanced to overcome metabolic stress. In this study, we investigated the role of Casein Kinase 2 (CK2) inhibition in macropinocytosis and subsequent metabolic processes in KRAS mutant cholangiocarcinoma (CCA) cell lines. MATERIALS AND METHODS: The bovine serum albumin (BSA) uptake indicating macropinocytosis was performed by flow cytometry using the HuCCT1 KRAS mutant CCA cell line. To validate macropinosome, the Rab7 and LAMP2 were labeled and analyzed via immunocytochemistry and western blot. The CX-4945 (Silmitasertib), CK2 inhibitor, was used to investigate the role of CK2 in macropinocytosis and subsequent lysosomal metabolism. RESULTS: The TFK-1, a KRAS wild-type CCA cell line, showed only apoptotic morphological changes. However, the HuCCT1 cell line showed macropinocytosis. Although CX-4945 induced morphological changes accompanied by the accumulation of intracellular vacuoles and cell death, the level of macropinocytosis did not change. These intracellular vacuoles were identified as late macropinosomes, representing Rab7+ vesicles before fusion with lysosomes. In addition, CX-4945 suppressed LAMP2 expression following the inhibition of the Akt-mTOR signaling pathway, which interrupts mature macropinosome and lysosomal metabolic utilization. CONCLUSION: Macropinocytosis is used as an energy source in the KRAS mutant CCA cell line HuCCT1. The inhibition of CK2 by CX-4945 leads to cell death in HuCCT1 cells through alteration of the lysosome-dependent metabolism.
Subject(s)
Bile Duct Neoplasms , Casein Kinase II , Cholangiocarcinoma , Lysosomes , Mutation , Naphthyridines , Phenazines , Pinocytosis , Piperazines , Proto-Oncogene Proteins p21(ras) , Humans , Lysosomes/metabolism , Cell Line, Tumor , Cholangiocarcinoma/pathology , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/genetics , Pinocytosis/drug effects , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Casein Kinase II/metabolism , Casein Kinase II/genetics , Casein Kinase II/antagonists & inhibitors , Piperazines/pharmacology , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/genetics , rab7 GTP-Binding Proteins/metabolism , Cell Death/drug effects , Apoptosis/drug effects , Lysosomal-Associated Membrane Protein 2/metabolism , Lysosomal-Associated Membrane Protein 2/genetics , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/geneticsABSTRACT
Knee osteoarthritis (OA), also known as degenerative arthritis, is a disease characterized by irreversible changes in the cartilage and bones comprising the joints, resulting in pain, impaired function, and deformity. Furthermore, independent of natural aging, the rate of change in joint cartilage has increased in recent years, which is mainly attributed to environmental factors. The rising incidence of knee-related disorders emphasizes the importance of analyzing the morphology and kinematics of knee structure. This study introduces a knee measurement system designed to replicate the motions of knee using 3D-printing technology, providing insights into knee mechanics with OA level. The research explores the stages of OA using the Kellgren-Lawrence (KL) grade scale, highlighting the variations in the force applied to the knee bone according to movement. The developed knee-simulation system, utilizing the four-bar-link theory, presents a novel approach to studying OA levels 0 to 4. As OA progresses, the cartilage deteriorates, affecting the movement of OA. The OA-based knee measurement system that incorporates soft tissues and skeletons can assist in developing a personalized diagnostic approach for knee disease. This will also help to enhance surgical effectiveness by facilitating the creation of personalized prosthetic joints for individual patients and offering a customized surgical simulation.
ABSTRACT
Textiles composed of fibers can have their mechanical properties adjusted by changing the arrangement of the fibers, such as strength and flexibility. Particularly, in the case of smart textiles incorporating active materials, various deformations could be created based on fiber patterns that determine the directivity of active materials. In this study, we design a smart fiber-based textile actuator with a chain structure and evaluate its actuation characteristics. Smart fiber composed of shape memory alloy (SMA) generates deformation when the electric current is applied, causing the phase transformation of SMA. We fabricated the smart chain column and evaluated its actuating mechanism based on the size of the chain and the number of rows. In addition, a crochet textile actuator was designed using interlooping smart chains and developed into a soft gripper that can grab objects. With experimental verifications, this study provides an investigation of the relationship between the chain actuator's deformation, actuating force, actuator temperature, and strain. The results of this study are expected to be relevant to textile applications, wearable devices, and other technical fields that require coordination with the human body. Additionally, it is expected that it can be utilized to configure a system capable of flexible operation by combining rigid elements such as batteries and sensors with textiles.
ABSTRACT
Shape memory alloys (SMAs) are smart materials that are widely used to create intelligent devices because of their high energy density, actuation strain, and biocompatibility characteristics. Given their unique properties, SMAs are found to have significant potential for implementation in many emerging applications in mobile robots, robotic hands, wearable devices, aerospace/automotive components, and biomedical devices. Here, the state-of-the-art of thermal and magnetic SMA actuators in terms of their constituent materials, form, and scaling effects are summarized, including their surface treatments and functionalities. The motion performance of various SMA architectures (wires, springs, smart soft composites, and knitted/woven actuators) is also analyzed. Based on the assessment, current challenges of SMAs that need to be addressed for their practical application are emphasized. Finally, how to advance SMAs by synergistically considering the effects of material, form, and scale is suggested.
ABSTRACT
Soft actuators that execute diverse motions have recently been proposed to improve the usability of soft robots. Nature-inspired actuators, in particular, are emerging as a means of accomplishing efficient motions based on the flexibility of natural creatures. In this research, we present an actuator capable of executing multi-degree-of-freedom motions that mimics the movement of an elephant's trunk. Shape memory alloys (SMAs) that actively react to external stimuli were integrated into actuators constructed of soft polymers to imitate the flexible body and muscles of an elephant's trunk. The amount of electrical current provided to each SMA was adjusted for each channel to achieve the curving motion of the elephant's trunk, and the deformation characteristics were observed by varying the quantity of current supplied to each SMA. It was feasible to stably lift and lower a cup filled with water by using the operation of wrapping and lifting objects, as well as effectively performing the lifting task of surrounding household items of varying weights and forms. The designed actuator is a soft gripper that incorporates a flexible polymer and an SMA to imitate the flexible and efficient gripping action of an elephant trunk, and its fundamental technology is expected to be used as a safety-enhancing gripper that requires environmental adaptation.
ABSTRACT
In recent years, many researchers have aimed to construct robotic soft grippers that can handle fragile or unusually shaped objects without causing damage. This study proposes a smart textile-composite actuator and its application to a soft robotic gripper. An active fiber and an inactive fiber are combined together using knitting techniques to manufacture a textile actuator. The active fiber is a shape memory alloy (SMA) that is wire-wrapped with conventional fibers, and the inactive fiber is a knitting yarn. A knitted textile structure is flexible, with an excellent structure retention ability and high compliance, which is suitable for developing soft grippers. A driving source of the actuator is the SMA wire, which deforms under heating due to the shape memory effect. Through experiments, the course-to-wale ratio, the number of bundling SMA wires, and the driving current value needed to achieve the maximum deformation of the actuator were investigated. Three actuators were stitched together to make up each finger of the gripper, and layer placement research was completed to find the fingers' suitable bending angle for object grasping. Finally, the gripping performance was evaluated through a test of grasping various object shapes, which demonstrated that the gripper could successfully lift flat/spherical/uniquely shaped objects.
ABSTRACT
As the use of drones grows, so too does the demand for physical protection against drone damage resulting from collisions and falls. In addition, as the flight environment becomes more complicated, a shock absorption system is required, in which the protective structure can be deformed based on the circumstances. Here, we present an origami- and kirigami-based structure that provides protection from various directions. This research adds a deformation capacity to existing fixed-shape guards; by using shape memory alloys, the diameter and height of the protective structure are controlled. We present three protective modes (1: large diameter/low height; 2: small diameter/large height; and 3: lotus shaped) that mitigate drone falls and side collisions. From the result of the drop impact test, mode 2 showed a 78.2% reduction in the maximum impact force at side impact. We incorporated kirigami patterns into the origami structures in order to investigate the aerodynamic effects of the hollow patterns. Airflow experiments yielded a macro understanding of flow-through behaviors on each kirigami pattern. In the wind speed experiment, the change in airflow velocity induced by the penetration of the kirigami pattern was measured, and in the force measurement experiment, the air force applied to the structure was determined.
ABSTRACT
Several composite materials are being investigated as reinforcement fillers for surgery simulations. This study presents an artificial composite material with properties similar to those of the human bone, which may be used in surgery simulations. Moreover, considering the potential toxicity of debris generated during sawing, a safe epoxy-based composite material was synthesized using cellulose nanocrystals (CNCs) and bioceramics (i.e., hydroxyapatite, Yttria stabilized zirconia oxide, Zirconia oxide), which were used to mimic the stiffness of human bone. To examine the change in mechanical properties according to the composition, 1, 3, and 5 wt% of CNCs were mixed with 5 wt% of the bioceramics. When CNCs were added at 1 wt%, there was a confirmed change in the non-linear stiffness and ductility. The CNC-added specimen fractured when forming a nano-network around the local CNCs during curing. In contrast, the specimen without CNCs was more densely structured, and combined to form a network of all specimens such that a plastic region could exist. Thus, this study successfully manufactured a material that could mimic longitudinal and transverse characteristics similar to those of real human bone, as well as exhibit mechanical properties such as strength and stiffness. Bioceramics are harmless to the human body, and can be used by controlling the added quantity of CNCs. We expect that this material will be suitable for use in surgery simulations.
ABSTRACT
Cachexia, which is characterised by the wasting of fat and skeletal muscles, is the most common risk factor for increased mortality rates among patients with advanced lung cancer. PTHLH (parathyroid hormone-like hormone) is reported to be involved in the pathogenesis of cancer cachexia. However, the molecular mechanisms underlying the regulation of PTHLH expression and the inhibitors of PTHLH have not yet been identified. The PTHLH mRNA levels were measured using quantitative real-time polymerase chain reaction, while the PTHrP (parathyroid hormone-related protein) expression levels were measured using Western blotting and enzyme-linked immunosorbent assay. The interaction between TCF4 (Transcription Factor 4) and TWIST1 and the binding of the TCF4-TWIST1 complex to the PTHLH promoter were analysed using co-immunoprecipitation and chromatin immunoprecipitation. The results of the mammalian two-hybrid luciferase assay revealed that emodin inhibited TCF4-TWIST1 interaction. The effects of Polygonum cuspidatum extract (Pc-Ex), which contains emodin, on cachexia were investigated in vivo using A549 tumour-bearing mice. Ectopic expression of TCF4 upregulated PTHLH expression. Conversely, TCF4 knockdown downregulated PTHLH expression in lung cancer cells. The expression of PTHLH was upregulated in cells ectopically co-expressing TCF4 and TWIST1 when compared with that in cells expressing TCF4 or TWIST1 alone. Emodin inhibited the interaction between TCF4 and TWIST1 and consequently suppressed the TCF4/TWIST1 complex-induced upregulated mRNA and protein levels of PTHLH and PTHrP. Meanwhile, emodin-containing Pc-Ex significantly alleviated skeletal muscle atrophy and downregulated fat browning-related genes in A549 tumour-bearing mice. Emodin-containing Pc-Ex exerted therapeutic effects on lung cancer-associated cachexia by inhibiting TCF4/TWIST1 complex-induced PTHrP expression.
Subject(s)
Emodin , Fallopia japonica , Lung Neoplasms , Animals , Cachexia/drug therapy , Cachexia/etiology , Cachexia/prevention & control , Emodin/pharmacology , Emodin/therapeutic use , Humans , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Mammals/genetics , Mammals/metabolism , Mice , Nuclear Proteins/genetics , Parathyroid Hormone-Related Protein/genetics , Plant Extracts , RNA, Messenger/metabolism , Transcription Factor 4/genetics , Twist-Related Protein 1/geneticsABSTRACT
The one-dimensional deformation of shape memory alloy (SMA) wires and springs can be implemented into different types of functional structures with three-dimensional deformations. These structures can be classified based on the type of structure and how the SMA element has been implemented into the following categories: rigid mechanical joints, semi-rigid flexural hinges, SMA elements externally attached to a soft structure, and embedded into the soft structure. These structures have a wide range of properties and implementation requirements, and they have been used to produce a variety of robots with rigid and soft motions. The different research efforts to develop actuators and robots related to each type of structure are presented along with their respective strengths and weaknesses. A model is then developed to discuss the performance and applicability of SMA wires versus SMA springs for actuators with a polymeric matrix to see the effect of each type of SMA on the selection of design parameters. A comparison of the different types of structures and the applicability of different types of SMA elements for different types of structures is then presented.
ABSTRACT
A loop-linked structure, which is capable of morphing in various modes, including volumetric transformation, is developed based on knitting methods. Morphing flowers (a lily-like, a daffodil-like, gamopetalous, and a calla-like flower) are fabricated using loop patterning, and their blooming motion is demonstrated by controlling a current that selectively actuates the flowers petals.
ABSTRACT
OBJECTIVES: The purpose of this study was to evaluate changes in the pharyngeal airway space and hyoid bone position after mandibular setback surgery with bilateral sagittal split ramus osteotomy (BSSRO) and to analyze the correlation between the amount of mandibular setback and the amount of change in pharyngeal airway space or hyoid bone position. MATERIALS AND METHODS: From January 2010 to February 2013, a total of 30 patients who were diagnosed with skeletal class III malocclusion and underwent the same surgery (BSSRO) and fixation method in the Division of Oral and Maxillofacial Surgery, Department of Dentistry at the Ajou University School of Medicine (Suwon, Korea) were included in this study. Lateral cephalograms of the 30 patients were assessed preoperatively (T1), immediately postoperatively (T2), and 6 months postoperatively (T3) to investigate the significance of changes by time and the correlation between the amount of mandibular setback and the amount of change in the airway space and hyoid bone position. RESULTS: Three regions of the nasopharynx, oropharynx, and hypopharynx were measured and only the oropharynx showed a statistically significant decrease (P<0.01). A significant posterior and inferior displacement of the hyoid bone was found 6 months after surgery (P<0.01). Analysis of the correlation between the amount of mandibular setback and the amount of final change in the airway space and hyoid bone position with Pearson's correlation showed no significant correlation. CONCLUSION: In this study, the oropharynx significantly decreased after mandibular setback surgery, and changes in the surrounding structures were identified through posteroinferior movement of the hyoid bone during long-term follow-up. Therefore, postoperative obstructive sleep apnea should be considered in patients who plan to undergo mandibular setback surgery, and necessary modifications to the treatment plan should also be considered.
ABSTRACT
Oxidative stress due to the over-production of reactive oxygen species (ROS) is associated with human skin aging. This study was designed to identify the bioactive phenolics in detoxified Rhus verniciflua Stokes (DRVS) that may protect human skin against oxidative stress. Under oxidative stress caused by H2O2, the 40% (v/v) aqueous methanol extract of DRVS protected human keratinocytes in a dose-dependent manner. The expression of matrix metalloproteinase-1 (MMP-1) was also inhibited by the DRVS extract in human dermal fibroblasts-neonatal cells exposed to ultraviolet A. The major bioactive phenolics of DRVS were tentatively identified by LC/Q-TOF-ESI-MS/MS, and included gallic acid, 2-(ethoxymethoxy)-3-hydroxyphenol, fustin, a fustin isomer, tetragalloyl glucose, pentagalloyl glucose, fisetin, sulfuretin, a sulfuretin isomer, and butein. The results suggest that a DRVS extract may be effective in slowing skin aging through its antioxidative properties and by down-regulating MMP-1 expression. Further studies are needed to examine whether this effect would be mediated by the phenolics identified in this study.
Subject(s)
Fibroblasts/drug effects , Keratinocytes/drug effects , Phenols/isolation & purification , Plant Extracts/pharmacology , Toxicodendron/chemistry , Cell Line , Fibroblasts/radiation effects , Gene Expression Regulation/drug effects , Humans , Hydrogen Peroxide/toxicity , Keratinocytes/radiation effects , Matrix Metalloproteinase 1/biosynthesis , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Phenols/chemistry , Phenols/pharmacology , Plant Extracts/chemistry , Reactive Oxygen Species , Tandem Mass Spectrometry , Ultraviolet RaysABSTRACT
Phenolics of the fresh ripe fruits of Rubus coreanus Miquel were extracted and separated into anthocyanin and the non-anthocyanin fractions, which were used for the evaluation for antioxidant capacity and neuroprotective effects. The anthocyanin fraction accounted for approximately 47-55% of the total antioxidant capacity of the whole extract and had significantly higher free radical-scavenging capacity than the non-anthocyanin fraction. Furthermore, the anthocyanins alleviated intracellular oxidative stress, as assayed by in vitro fluorescent measurements. The anthocyanins showed neuroprotective effects on PC-12 cells in vitro against oxidative stress in a dose-dependent manner. Triple quadrupole LC/MS and Q-TOF LC/MS analyses revealed four major anthocyanins; cyanidin 3-O-sambubioside, cyanidin 3-O-glucoside, cyanidin 3-O-xylosylrutinoside, and cyanidin 3-O-rutinoside in increasing order of amounts. These results demonstrated that anthocyanins are the major components and contributors to the antioxidant capacity of ripe R. coreanus Miquel fruits. Further studies are warranted to determine whether consumption of the fruits reduces oxidative stress in the brain and promotes health.
Subject(s)
Anthocyanins/pharmacology , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Rosaceae/chemistry , Animals , Anthocyanins/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Chromatography, High Pressure Liquid , Fruit/chemistry , Mass Spectrometry , Neurons/cytology , Neuroprotective Agents/chemistry , PC12 Cells , Plant Extracts/chemistry , RatsABSTRACT
Eotaxin is an important inflammatory chemokine in eosinophil chemotaxis and activation and, thus, is implicated in asthma. Recently, obesity was associated with an increased prevalence of asthma, but the relationship between obesity and eotaxin expression has only been partially understood in obese mice and human studies. Therefore, we studied the expression patterns of eotaxin in 3T3-L1 preadipocytes/adipocytes to determine whether eotaxin levels are influenced by body weight gain and/or reduction in diet-induced obese mice. First, we investigated eotaxin expression during differentiation in 3T3-L1 adipocytes. Then, we treated 3T3-L1 preadipocytes/adipocytes with tumor necrosis factor-alpha (TNF-α), eotaxin, interleukin (IL)-4, IL-5, or leptin. To examine the effects of weight loss in high-fat diet induced obese mice, we fed C57BL/6 mice a high-fat diet or a normal diet for 26 weeks. Then, half of the high-fat diet group were fed a normal diet until 30 weeks to reduce weight. Epididymal adipose tissue, visceral adipose tissue, serum, and bronchoalveolar fluid of mice were examined for eotaxin expression. The results showed that eotaxin expression levels increased with adipocyte differentiation and that more eotaxin was expressed when the cells were stimulated with TNF-α, eotaxin, IL-4, IL-5, or leptin. An in vivo study showed that eotaxin levels were reduced in visceral adipose tissues when high-fat diet fed mice underwent weight loss. Taken together, these results indicate a close relationship between eotaxin expression and obesity as well as weight loss, thus, they indirectly show a relation to asthma.
ABSTRACT
Repeated silica gel and octadecyl silica gel (ODS) column chromatography of the aerial parts of Artemisia princeps PAMPANINI (Sajabalssuk) led to the isolation of a new sesquiterpenoid, 3-((S)-2-methylbutyryloxy)-costu-1(10),4(5)-dien-12,6 alpha-olide (2), along with two previously reported sesquiterpenoids: 8 alpha-angeloyloxy-3beta,4 beta-epoxy-6 beta H,7 alpha H,8 beta H-guaia-1(10),11(13)-dien-12,6 alpha-olide (1, carlaolide B) and 3beta,4 beta-epoxy-8 alpha-isobutyryloxy-6 beta H,7 alpha H,8 beta H-guaia-1(10),11(13)-dien-12,6 alpha-olide (3, carlaolide A). The structure of compound 2 was elucidated by spectroscopic data analysis, including one dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) experiments. Of the isolates, compound 2 exhibited potent cytotoxicity against human cervix adenocarcinoma cells and induced apoptosis.