Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes.
Early development of liver cancer is usually asymptomatic. The overall survival rate of patients is relatively low due to late diagnosis, despite hepatocellular carcinoma being a common diagnosis. The high mortality rate of liver cancer was due to its overactivated cellular mitochondrial activities, namely thioredoxin reductase enzymatic activities and its downstream activation of nuclear factor kappa B (NF-κB) signaling pathways for cancer cell migration. Our previous study on this candidate compound on A2780 ovarian cancer cells and MCF-7 breast cancer cells, through modulation of cell-cycle checkpoints and respective targeted apoptosis pathways. The current study used HepG2 hepatocellular carcinoma cell lines as a representative in vitro liver cancer cell model. The half maximal inhibitory concentration (IC50) value was obtained via incubation of PTZ compound for 24 h yield of 37.03 μM, whereby it was three-fold more potent than the standard control tested, cisplatin (109.23 μM). The subsequent application of IC50 dosage of PTZ onto HepG2 cells illustrated a growth-static effect via activation of S-phase cell-cycle checkpoints, immediately followed by regulation of apoptosis. Increased cellular concentration of reactive oxygen species eventually generated oxidative damages on mitochondria, hence resulting in the release of cytochrome c protein and suppression of TrxR enzymatic activity, in conjunction with the suppression on invasion of cancer cells via Matrigel invasion chamber. In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research.
Metastasis contributes to the escalating mortality rate among cancer patients worldwide. The search for novel and more effective anti-metastatic agent is crucial owing to the lack of anticancer drugs that can successfully combat metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4-Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion assays, the number of cells permeating across a Matrigel barrier was found to be decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 μM). In wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell migration in which significant reduction in the zone of closure was observed as compared to untreated controls. Furthermore, the proteolytic activity of a pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also downregulated by MNQ as determined by gelatin zymography. This study reports for the first time, the ability of MNQ to inhibit the invasion and migration characteristics of a highly metastatic MDA-MB-231 cancer cell line.
Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line.
Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
Transparent object detection and reconstruction are significant, due to their practical applications. The appearance and characteristics of light in these objects make reconstruction methods tailored for Lambertian surfaces fail disgracefully. In this paper, we introduce a fixed multi-viewpoint approach to ascertain the shape of transparent objects, thereby avoiding the rotation or movement of the object during imaging. In addition, a simple and cost-effective experimental setup is presented, which employs two single-pixel detectors and a digital micromirror device, for imaging transparent objects by projecting binary patterns. In the system setup, a dark framework is implemented around the object, to create shades at the boundaries of the object. By triangulating the light path from the object, the surface shape is recovered, neither considering the reflections nor the number of refractions. It can, therefore, handle transparent objects with a relatively complex shape with the unknown refractive index. The implementation of compressive sensing in this technique further simplifies the acquisition process, by reducing the number of measurements. The experimental results show that 2D images obtained from the single-pixel detectors are better in quality with a resolution of 32×32. Additionally, the obtained disparity and error map indicate the feasibility and accuracy of the proposed method. This work provides a new insight into 3D transparent object detection and reconstruction, based on single-pixel imaging at an affordable cost, with the implementation of a few numbers of detectors.
We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient's disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.
Cell adhesion is essential in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues. The mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. The essential function of cell adhesion has created tremendous interests in developing methods for measuring and studying cell adhesion properties. The study of cell adhesion could be categorized into cell adhesion attachment and detachment events. The study of cell adhesion has been widely explored via both events for many important purposes in cellular biology, biomedical, and engineering fields. Cell adhesion attachment and detachment events could be further grouped into the cell population and single cell approach. Various techniques to measure cell adhesion have been applied to many fields of study in order to gain understanding of cell signaling pathways, biomaterial studies for implantable sensors, artificial bone and tooth replacement, the development of tissue-on-a-chip and organ-on-a-chip in tissue engineering, the effects of biochemical treatments and environmental stimuli to the cell adhesion, the potential of drug treatments, cancer metastasis study, and the determination of the adhesion properties of normal and cancerous cells. This review discussed the overview of the available methods to study cell adhesion through attachment and detachment events.
Loss of the ability to speak or hear exerts psychological and social impacts on the affected persons due to the lack of proper communication. Multiple and systematic scholarly interventions that vary according to context have been implemented to overcome disability-related difficulties. Sign language recognition (SLR) systems based on sensory gloves are significant innovations that aim to procure data on the shape or movement of the human hand. Innovative technology for this matter is mainly restricted and dispersed. The available trends and gaps should be explored in this research approach to provide valuable insights into technological environments. Thus, a review is conducted to create a coherent taxonomy to describe the latest research divided into four main categories: development, framework, other hand gesture recognition, and reviews and surveys. Then, we conduct analyses of the glove systems for SLR device characteristics, develop a roadmap for technology evolution, discuss its limitations, and provide valuable insights into technological environments. This will help researchers to understand the current options and gaps in this area, thus contributing to this line of research.
The compound with R=CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R=CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes.
Human motion is a daily and rhythmic activity. The exoskeleton concept is a very positive scientific approach for human rehabilitation in case of lower limb impairment. Although the exoskeleton shows potential, it is not yet applied extensively in clinical rehabilitation. In this research, a fuzzy based control algorithm is proposed for lower limb exoskeletons during sit-to-stand and stand-to-sit movements. Surface electromyograms (EMGs) are acquired from the vastus lateralis muscle using a wearable EMG sensor. The resultant acceleration angle along the z-axis is determined from a kinematics sensor. Twenty volunteers were chosen to perform the experiments. The whole experiment was accomplished in two phases. In the first phase, acceleration angles and EMG data were acquired from the volunteers during both sit-to-stand and stand-to-sit motions. During sit-to-stand movements, the average acceleration angle at activation was 11°-48° and the EMG varied from -0.19 mV to +0.19 mV. On the other hand, during stand-to-sit movements, the average acceleration angle was found to be 57.5°-108° at the activation point and the EMG varied from -0.32 mV to +0.32 mV. In the second phase, a fuzzy controller was designed from the experimental data. The controller was tested and validated with both offline and real time data using LabVIEW.
Autonomous agents are being widely used in many systems, such as ambient assisted-living systems, to perform tasks on behalf of humans. However, these systems usually operate in complex environments that entail uncertain, highly dynamic, or irregular workload. In such environments, autonomous agents tend to make decisions that lead to undesirable outcomes. In this paper, we propose a fuzzy-logic-based adjustable autonomy (FLAA) model to manage the autonomy of multi-agent systems that are operating in complex environments. This model aims to facilitate the autonomy management of agents and help them make competent autonomous decisions. The FLAA model employs fuzzy logic to quantitatively measure and distribute autonomy among several agents based on their performance. We implement and test this model in the Automated Elderly Movements Monitoring (AEMM-Care) system, which uses agents to monitor the daily movement activities of elderly users and perform fall detection and prevention tasks in a complex environment. The test results show that the FLAA model improves the accuracy and performance of these agents in detecting and preventing falls.
The phonetic properties of six Malay vowels are investigated using magnetic resonance imaging (MRI) to visualize the vocal tract in order to obtain dynamic articulatory parameters during speech production. To resolve image blurring due to the tongue movement during the scanning process, a method based on active contour extraction is used to track tongue contours. The proposed method efficiently tracks tongue contours despite the partial blurring of MRI images. Consequently, the articulatory parameters that are effectively measured as tongue movement is observed, and the specific shape of the tongue and its position for all six uttered Malay vowels are determined.Speech rehabilitation procedure demands some kind of visual perceivable prototype of speech articulation. To investigate the validity of the measured articulatory parameters based on acoustic theory of speech production, an acoustic analysis based on the uttered vowels by subjects has been performed. As the acoustic speech and articulatory parameters of uttered speech were examined, a correlation between formant frequencies and articulatory parameters was observed. The experiments reported a positive correlation between the constriction location of the tongue body and the first formant frequency, as well as a negative correlation between the constriction location of the tongue tip and the second formant frequency. The results demonstrate that the proposed method is an effective tool for the dynamic study of speech production.
Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts.
A prior screening programme carried out using MTT assay by our group identified a series of novel benzimidazole derivatives, among which Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) showed highest anticancer efficacy compared to that of chemotherapeutic agent, cisplatin. In the present study, we found that MBIC inhibited cell viability in different hepatocellular carcinoma (HCC) cell lines without exerting significant cytotoxic effects on normal liver cells. Annexin V-FITC/PI flow cytometry analysis and Western blotting results indicated that MBIC can induce apoptosis in HCC cells, which was found to be mediated through mitochondria associated proteins ultimately leading to the activation of caspase-3. The exposure to MBIC also resulted in remarkable impairment of HCC cell migration and invasion. In addition, treatment with MBIC led to a rapid generation of reactive oxygen species (ROS) and substantial activation of c-Jun-N-terminal kinase (JNK). The depletion of ROS by N-Acetyl cysteine (NAC) partially blocked MBIC-induced apoptosis and JNK activation in HCC cells. Finally, MBIC significantly inhibited tumor growth at a dose of 25 mg/kg in an orthotopic HCC mouse model. Taken together, these results demonstrate that MBIC may inhibit cell proliferation via ROS-mediated activation of the JNK signaling cascade in HCC cells.
In this study the novel caryophyllene type sesquiterpene lactone (aspfalcolide) has been isolated from the leaves of Asparagus falcatus (Linn.) and characterized by IR, 1D NMR, 2D NMR, EI-MS, HR-ESI-MS and X-ray single crystal diffraction analysis. The aspfalcolide crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 6.37360(10), b = 7.6890(2), c = 27.3281(6) Å, α = β = γ = 90(°) and Z = 4. One intermolecular O-H⋯O hydrogen bond enforces these natural molecules to form infinite chains through the crystal. Aspfalcolide was screened for its anti-angiogenic activity in human umbilical vein endothelial cells (HUVECs) and the result showed the remarkable inhibitory effect of aspfalcolide on the proliferation (IC(50) 1.82 μM), migration and tube formation of HUVECs.
Functional Electrical Stimulation (FES) can be used to revive movement
functions of the human body to a certain degree which was lost due to
occurrences of the nervous system disorders resulting from accidents or
diseases. It can also be employed for gait rehabilitation as well as therapy.
Control systems could be employed to improve on the FES-induced motion,
and the closed-loop was targeted due to its advantages. Based on the papers
reviewed, studies have shown that the linear control schemes are popular for
movement restoration in the lower limb, but mostly for continuous standing
contributing to mainly the stance phase. Therefore, a myriad of limitations
was observed which include: the need for using improved sensors, re-tuning
for every subject, tests conducted using patient with more straightforward
ailments, complexity in implementation and most importantly is the issue of
stability. The swing phase of gait movement and the full walking motion have
more complex dynamics and coupled with the nature of the plant (human with
nervous system disorder and the neuromuscular structure) could render the
linear control method obsolete or unsuitable. Hence, there is a need to
investigate other techniques such as the nonlinear and intelligent control
methods.
The transwell migration assay is commonly used for assessing cell migration. It involves the enumeration of cells that
have migrated across a pore-containing membrane. We describe a randomised approach to quantifying migrated
cells and compare it to a conventional full cell count. We used ATP as a chemoattractant and automatic cell quantification performed on all fields (Full count; FC) or 10 randomly selected fields (Randomised count; RC). The two
methods were compared by evaluating standard deviations (SD), coefficient of variation (CV) and using the Bland-Altman analysis. The dispersion of data is higher with the RC approach (3.77-6.66% CV for control; 3.89-4.48% CV
for ATP-treated wells) compared to FC (0.27-0.46% CV for control; 0.05-0.09% CV for ATP-treated wells), but are
acceptable considering that the number of migrated cells are in the thousands. Both methods verified that an ATP
migration assay for BV2 microglia was established, demonstrating that the RC approach is reliable and comparable
to a full count.
Good badminton lunge skills have been quantitatively described using biomechanical attributes at both static and dynamic phases. The measurement of badminton lunge attributes has often been complicated by various experimental protocols used. No review article has considered or critically reviewed the attributes that align with badminton lunge performance. This paper, hence, presents a review of badminton lunge postures governed by various determinant attributes. This review was performed by involving a number of relevant search engines. A total of 21 articles that fulfilled the predefined inclusion criteria were analysed. The lunge determinant attributes, such as time, lunge distance, plantar, ground reaction force, joint, dynamic balance and muscle attributes, had been examined. Contradictory findings in the dynamic balance attributes, specifically the relative displacement between the centre of mass and the centre of pressure, are presented in this paper. The findings showed that time, lunge distance and ground reaction force determined lunge performance. On the other hand, plantar, joint, dynamic balance and muscle attributes appeared useful in minimising injuries to ensure efficient lunge performance.
A fracture, which mostly results from a fall, is fatal for the elderly. A fall occurred when a person cannot maintain the
body position. Most falls occurred when a person walks on a slippery surface or trips over an object on the ground during
a gait. Most people try to avoid falls instinctively and fall when their attempt fails. As such, this study investigated the
difference between two movements- a movement to avoid falls and a forward-falling movement without a fall-avoiding
movement- by analyzing the body movements of the subjects. A fast-moving fall-guiding device with a pneumatic actuator
was used to guide falls. The movement of the device could simulate a foot slip that may happen during daily activities.
A three-axis acceleration sensor and a Bluetooth module were used to avoid disturbing the body movement during a fall
as a wire sensor or a movement analysis system does.