Abstract Objectives: This project aimed to develop an approach to evaluating information contained in the premodern Traditional Chinese Medicine (TCM) literature that was (1) comprehensive, systematic, and replicable and (2) able to produce quantifiable output that could be used to answer specific research questions in order to identify natural products for clinical and experimental research. Methods: The project involved two stages. In stage 1, 14 TCM collections and compendia were evaluated for suitability as sources for searching; 8 of these were compared in detail. The results were published in the Journal of Alternative and Complementary Medicine. Stage 2 developed a text-mining approach for two of these sources. Results: The text-mining approach was developed for Zhong Hua Yi Dian; Encyclopaedia of Traditional Chinese Medicine, 4th edition) and Zhong Yi Fang Ji Da Ci Dian; Great Compendium of Chinese Medical Formulae). This approach developed procedures for search term selection; methods for screening, classifying, and scoring data; procedures for systematic searching and data extraction; data checking procedures; and approaches for analyzing results. Examples are provided for studies of memory impairment and diabetic nephropathy, and issues relating to data interpretation are discussed. Conclusions: This approach to the analysis of large collections of the premodern TCM literature uses widely available sources and provides a text-mining approach that is systematic, replicable, and adaptable to the requirements of the particular project. Researchers can use these methods to explore changes in the names and conceptions of a disease over time, to identify which therapeutic methods have been more or less frequently used in different eras for particular disorders, and to assist in the selection of natural products for research efforts.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) regulates blood pressure and is important for the development of inflammation, oxidative stress and autophagy. We posited that LOX-1 via NADPH oxidase activation may affect autophagy and Toll-like receptor (TLR)4 expression in the brains of hypertensive mice.
The anatomic variation of Circle of Willis (CoW) has great impact on its compensatory capacity during stroke and cerebral ischemia. In the present study, a series of lumped parameter models were developed and used to simulate the effect of postural changes on the cerebral blood flow in ICA stenosis patients with different anatomic variants of the CoW. The results showed that the asymmetric distribution of cerebral blood flow caused by stenosis was attenuated in standing position in complete and half-complete CoW. However, in incomplete CoW, the decrease in blood flow in the ipsilateral cerebral arteries caused by unilateral ICA stenosis was dramatic in both supine and standing positions, a likely result of inadequate collateral circulation within the CoW. In conclusion, the anatomic variation of CoW plays a significant role in maintaining the balance of cerebral blood supply in patients with ICA stenosis, especially during postural change.
Polydimethylsiloxane (PDMS) and hydroxyapatite (HA) were combined in our laboratory to fabricate an elastic porous cell scaffold with pore-forming agent, and then the scaffold was used as culture media for rat bone marrow derived mesenchymal stem cells (rBMSCs). Different porous materials (square and circular in shape) were prepared by different pore-forming agents (NaCl or paraffin spheres) with adjustable porosity (62%-76%). The HA crystals grew on the wall of hole when the material was exposed to SBF solutions, showing its biocompatibility and ability to support the cells to attach on the materials.
This paper is to report our study in which the differences between prosthetic restoration and surgical reconstruction using traditional clasp retention technology were analyzed based on three-dimensional finite element methods in our laboratory. Firstly, the maxillary unilateral defect model was developed using medical image processing software MIMICS. Secondly, the prosthesis was generated by mirroring technology. The clasp was designed according to the methods raised by Aramany. Then, the stress distribution of maxilla was calculated by simulating occlusion. According to the results, after osseointegration of surgical reconstruction, stresses of unaffected abutments were reduced significantly, and less stress of junction occurred near zygoma of affected side, which were all less than stresses of prosthesis restoration. Thus, removing the clasp of surgical reconstruction increased the stresses of unaffected abutments. The stress trends of maxillary components were different between prosthetic restoration and surgical reconstruction. Surgical reconstruction is better than prosthesis restoration in protection of the abutments. Clasp can alleviate the occlusal burden of maxilla. Varieties of retentive technologies can be considered in prosthesis restoration. The surgical reconstruction is more conducive to rehabilitate unilateral maxilla biomechanically in clinic.
Helical flow in the human aorta is possibly a typical example of 'form follows function' in the vascular system. The helical blood flow may provide guaranties for the inner surface of the ascending aortic wall to get smooth and even washing by the blood so that atherosclerotic plaques can hardly form in the area of the ascending aorta. It has been documented that the phenomenon of helical flow of blood is not just localized in the ascending aorta, it also exists in several large arteries and veins as well. Preliminary studies demonstrated the widely existing helical flow might play positive physiological roles in facilitating blood flow transport, suppressing disturbed blood flow, preventing the accumulation of atherogenic low density lipoproteins on the luminal surfaces of arteries, enhancing oxygen transport from the blood to the arterial wall and reducing the adhesion of blood cells on the arterial surface. These roles of helical blood flow may lessen the burden of arteries and protect the arteries from the pathology of atherosclerosis, thrombosis, and intimal hyperplasia. The great development of time-resolved three-dimensional phase contrast MRI (flow-sensitive 4D-MRI) and the advent of dimensionless indices such as helical flow index proposed to characterize helical flow make clinic quantification of the helical flow in the human large arteries possible. Moreover, researchers probed into the possibility to apply the mechanism of helical flow to the design of vascular interventions to reduce thrombus formation and intimal hyperplasia caused by abnormal flow conditions.
Patellofemoral (PF) maltracking is a critical factor predisposing to PF pain syndrome. Many novel techniques of measuring patellar tracking remain research tools. This study aimed to develop a method to measure the in vivo patellar tracking and finite helical axis (FHA) by using a static magnetic resonance (MR) based methodology. The geometrical models of PF joint at 0°, 45°, 60°, 90°, and 120° of knee flexion were developed from MR images. The approximate patellar tracking was derived from the discrete PF models with a spline interpolation algorithm. The patellar tracking was validated with the previous in vitro and in vivo experiments. The patellar FHA throughout knee flexion was calculated. In the present case, the FHA drew an "L-shaped" curve in the sagittal section. This methodology could advance the examination of PF kinematics in clinics, and may also provide preliminary knowledge on patellar FHA study.
Previous studies have suggested that amnestic mild cognitive impairment (aMCI) is associated with changes in cortical morphological features, such as cortical thickness, sulcal depth, surface area, gray matter volume, metric distortion, and mean curvature. These features have been proven to have specific neuropathological and genetic underpinnings. However, most studies primarily focused on mass-univariate methods, and cortical features were generally explored in isolation. Here, we used a multivariate method to characterize the complex and subtle structural changing pattern of cortical anatomy in 24 aMCI human participants and 26 normal human controls. Six cortical features were extracted for each participant, and the spatial patterns of brain abnormities in aMCI were identified by high classification weights using a support vector machine method. The classification accuracy in discriminating the two groups was 76% in the left hemisphere and 80% in the right hemisphere when all six cortical features were used. Regions showing high weights were subtle, spatially complex, and predominately located in the left medial temporal lobe and the supramarginal and right inferior parietal lobes. In addition, we also found that the six morphological features had different contributions in discriminating the two groups even for the same region. Our results indicated that the neuroanatomical patterns that discriminated individuals with aMCI from controls were truly multidimensional and had different effects on the morphological features. Furthermore, the regions identified by our method could potentially be useful for clinical diagnosis.
Fixation and vascularity after bone fracture are two critical factors for successful healing, and their influences on bone healing have been studied by many researchers. This research aims to obtain three-dimensional (3D) reconstruction images of neovascularization of the soft tissues surrounding the fracture with vascular perfusion and micro-computer tomography (micro-CT) imaging, and to investigate the effect of stable fixation on neovascularization and the pattern of vascularity during the process of bone healing. To accomplish this, 36 Sprague-Dawley (SD) rats underwent mid-shaft transverse osteotomy of the right tibia. Half of them received stable fixation with a newly custom-designed external fixator (FSF, the group of fracture with stable fixation), while the rest received no fixation (FNF, the group of fracture with no fixation). The results indicated that FNF samples had more transversal vascular distribution than FSF samples; FSF samples had more longitudinal vascular distribution than FNF samples; and the spatio-temporal pattern of vascularity in FSF samples was more similar to that in the control group (CON, the group without fracture) than that in FNF samples. At the time of 2 and 4 weeks postoperatively, FNF samples had significantly higher vessel volume ratio (VV/TV), larger vessel number (VN) and higher vessel surface density (VS/TV) than CON samples. At all sacrifice times, FSF samples contained significantly higher VV/TV, VN and VS/TV values compared with FNF samples. In summary, neovascularization and its pattern are obviously influenced by the mechanical fixation. Stable fixation can promote longitudinal vascularity pattern formation, which tends to be similar to the natural vascularity pattern, and this benefits the inter-fragmentary blood fluid connectivity during bone healing process.
Circle of Willis (CoW) plays a significant role in maintaining the blood supply for the brain. Specifically, when the stenosis occurs in the internal carotid artery (ICA), abnormal structures of CoW would decrease the compensatory capacity, leading to the local insufficiency of cerebral blood supply. The present paper built a series of lumped parameter models for CoW, and simulated the blood redistribution caused by the unilateral ICA stenosis with different severities in cerebral arteries in the normal and abnormal CoW respectively. The results showed that when unilateral ICA stenosis occurred, the collateral circulation was built through the anterior communicating artery and the ipsilateral posterior communicating artery, maintaining the flow in cerebral arteries. The absence of the two communicating arteries would cause an obvious decrease of flow in local cerebral arteries in the anterior circulation. In conclusion, the two arteries play a significant role in maintaining the balance of cerebral blood supply in the development of ICA stenosis.
To test the hypothesis that the venous graft when implanted in an arterial bypass might endure a significantly elevated water filtration rate, leading to fast infiltration/accumulation of low-density lipoproteins (LDLs) within the graft wall and hence the accelerated atherogenesis.
This paper proposed a mobile vital-signs monitoring system based on ZigBee localization and wireless transmission technology for the elderly in nursing home. The system can monitor the vital-signs (pulse, ECG and blood oxygen), localize human body and warn in emergency. The validity and accuracy of this system were testified by the experiments of mobile acquisition and storage of pulse. In these experiments, the measurement of pulse ranged from 50 to 170 time a minute, the mean error of which was less than 3%. The mean error of localizing was less than 4 m. And the data transmission rate was 250 kbps. The system, which effectively conducts the real-time monitoring of the health and safety situation for the elderly, has a great significance for protecting the elderly's life safety.
Eighty-five percentage of the population has ever experienced low back pain (LBP), which would result in decreasing of muscle strength and endurance, functional capacity of the spine and so on. Traction and vibration were commonly used to relieve the low back pain. It was investigated that the effect of the combing traction and vibration on back muscles, heart rate (HR) and blood pressure (BP) in this study. Thirty healthy subjects participated in 12 trials lying supine on the spine combing bed with different tilt angle (0°, 10°, 20° and 30°) and vibration modes (along with the sagittal and coronal axis with 0Hz, 2Hz and 12Hz separately). EMG was recorded during each trial. Power spectral frequency analysis was applied to evaluate muscle fatigue by the shift of median power frequency (MPF). Pulse pressure (PP) was calculated from BP. HR and PP were used to estimate the effect of the combination of traction and vibration on cardio-vascular system. It was shown that vibration could increase HR and decrease PP. The combination of traction and vibration (2Hz vibration along Z-axis and 12Hz vibration along Y-axis) might have no significant effect on cardio-vascular system. The MPF of LES and UT decreased significantly when the angle reached 20° under the condition of 2Hz vibration along Z-axis compared with it of 0°. What's more, the MPF also decreased significantly compared with it of static mode at 20° for LES and at 30° for UT. However at 12Hz vibration along Y-axis, the MPF had significant increase when the angle reached 20° in LES and 30° in UT compared to it of 0°. For LES, the MPF also had significant difference when the angle was added from 10° to 20°. Therefore, when the 2Hz vibration along Z-axis and traction (tilt angles that less than 20°) were combined, it was helpful to reduce muscle fatigue both for LES and UT compared with only vibration or traction. When the 12Hz vibration along Y-axis and traction (tilt angles that more than 10° for LES and more than 20° for UT) were combined, it could provide good treatment with lower muscle fatigue for back pain compared with only vibration or traction. It is helpful to provide biomechanical quantitative basis for the selection of the clinical treatment methods.
The calcification initiation and progression of bioprosthetic heart valve were investigated in a rat model by enhanced micro-computed tomography, together with histologic study and scanning electron microscope analysis. The implantation data at early stage showed apparent dendritic patterns in the radiographic images for the glutaraldehyde-treated bovine pericardium and this dendritic pattern was verified to be associated with the vessel distribution in the tissue. Histologic study and scanning electron microscope analysis both indicated that the calcium deposits in the pericardium vessels regions were more grievous than those scattered in the collagen fibers in the first two weeks after implantation. Subsequently, calcification spreaded and the entire sample was severely calcified in 60 days.
Immediate loading (IL) increases the risk of marginal bone loss. The present study investigated the biomechanical response of peri-implant bone in rabbits after IL, aiming at optimizing load management. Ninety-six implants were installed bilaterally into femurs of 48 rabbits. Test implants on the left side created the maximal initial stress of 6.9 and 13.4 MPa in peri-implant bone and unloaded implants on the contralateral side were controls. Bone morphology and bone-implant interface strength were measured with histological examination and push-out testing during a 12-week observation period. Additionally, the animal data were incorporated into finite element (FE) models to calculate the bone stress distribution at different levels of osseointegration. Results showed that the stress was concentrated in the bone margin and the bone stress gradually decreased as osseointegration proceeded. A stress of about 2.0 MPa in peri-implant bone had a positive effect on new bone formation, osseointegration and bone-implant interface strength. Bone loss was observed in some specimens with stress exceeding 4.0 MPa. Data indicate that IL significantly increases bone stress during the early postoperative period, but the load-bearing capacity of peri-implant bone increases rapidly with an increase of bone-implant contact. Favorable bone responses may be continually promoted when the stress in peri-implant bone is maintained at a definite level. Accordingly, the progressive loading mode is recommended for IL implants.
Lectin-like ox-LDL scavenger receptor-1 (LOX-1) and mitochondrial DNA (mtDNA) damage play a key role in a variety of cardiovascular diseases, including atherosclerosis, hypertension, and inflammation. We posited that damaged mtDNA could trigger autophagy and NLRP3 inflammasome activation, and LOX-1 may play a critical role in this process.
Previous animal studies by using tail-suspended hindlimb-unloaded rat model have shown that simulated microgravity-induced vessel structural and functional remodeling may be anatomic region dependent. However, little care has been taken to assess the structural adaptation of the endothelial glycocalyx, the apical surface of the endothelium, the key mechanosensor mediating nitric oxide (NO) production, and the natural protective barrier of the vasculature. Therefore, the present study extended simulated microgravity-induced vessel remodeling to the endothelial glycocalyx level. The percents of bone mineral density (BMD) change from both control and tail-suspended (TS) rats were measured by micro-computed tomography (Micro-CT). Structural parameters such as the luminal diameter (D), the thickness of each layer, the ratio of intima to media (IMR), the cross-sectional areas of the intima (CSAI) and media (CSAM) of vessels from three different regions (the common carotid artery, abdominal aorta, and femoral artery) were assessed by hematoxylin and eosin staining. Dimensions of the glycocalyx above, below, and away from the endothelial cell nucleus were examined by fluorescein isothiocyanate-labeled wheat germ agglutinin (WGA-FITC) binding to the cryosection of vessels. Our results show that 3-week tail suspension of rats increases the thickness and CSA of the abdominal aortic endothelium by 23.7 and 21.1 %, respectively, thickens the media layer of the common carotid artery by 34.0 %, and increases the luminal diameter, the CSA of the intima and media of the femoral artery by 75.7, 93, and 61.2 %, respectively. Correspondingly, the dimension of the glycocalyx away from the common carotid arterial and the abdominal aortic endothelial cell nucleus from tail-suspended rats shows a 1.66- and 1.64-fold increase respectively, while it shows a 0.79-fold reduction on the top of the femoral endothelial cells. These results suggest that simulated microgravity induces vascular endothelial glycocalyx remodeling in a regional-dependent manner. The perturbation of the endothelial glycocalyx at the lower body artery may be the first event of vascular remodeling initiating endothelial dysfunction, contributing to postspaceflight orthostatic intolerance.
A series of thienopyridinone derivatives was designed and synthesized as inhibitors of checkpoint kinase 1 (Chk1). Most of them exhibited moderate to good Chk1 inhibitory activities. Among them, compounds 8q, 8t, and 8w with excellent Chk1 inhibitory activities (IC50 values of 4.05, 6.23, and 2.33nM, respectively) displayed strong synergistic effects with melphalan, a DNA-damaging agent in the cell-based assay. Further kinase profiling indicated that compound 8t was highly selective against CDK2/cyclinA, Aurora A, and PKC.
The paper discussed the protective effect of zinc pretreatment on renal ischemia-reperfusion injury (RIRI) and its mechanism. 50 male ICR mice were randomly divided into five groups: sham-operated group, model group, high-dose group with zinc sulfate pretreatment (60mg/kg body weight), medium-dose group with zinc sulfate pretreatment (30mg/kg body weight) and low-dose group with zinc sulfate pretreatment (15mg/kg body weight). The mice were administrated with zinc sulfate once a day for two weeks, subsequently the RIRI animal models were prepared by ligation of the left renal pedicle 30 minutes. 24h after reperfusion, the kidney tissue was removed and pathological results by HE staining showed that in the model group, kidney surface covered with a large number of red exudates, renal tubular dilatated, disorganized, renal tubular epithelial cell vacuolar degenerated, nuclear pyknosis and necrosis appeared; congestive and necrosis were visible in medullary junction. The pathological changes of renal ischemia- reperfusion were obviously relieved in the animals with medium and low-dose zinc pretreatment. The superoxide dismutase (SOD) activity in the lowdose zinc sulfate pretreatment group was significantly higher than that in the model and high-dose groups (P <0.05). The malondialdehyde (MDA) content of renal tissue, the apoptotic cells percentage in the medium and low dose groups were significantly lower than those in the model group (P <0.05), and MDA content in the low-dose group was significantly lower than that in the medium dose group (P <0.05). The ratio of BCL-2/BAX protein expression in the medium and low dose groups was significantly higher than that in the model group (P<0.05), the ratio in the low groups was significantly higher than that in the medium dose and high dose group by double immunofluorescence staining (P <0.05). In conclusion, zinc has a protective effect on the renal ischemia-reperfusion injury by antioxidant capacity and inhibition of apoptosis in the kidney.
Heat generated during bone drilling could cause irreversible thermal damage, which can lead to bone necrosis or even osteomyelitis. In this study, vibrational drilling was applied to fresh bovine bones to investigate the cutting heat in comparison with conventional drilling through experimental investigation and finite element analysis (FEA). The influence of vibrational frequency and amplitude on cutting heat generation and conduction were studied. The experimental results showed that, compared with the conventional drilling, vibrational drilling could significantly reduce the cutting temperature in drilling of cortical bone (P<0.05): the cutting temperature tended to decrease with increasing vibrational frequency and amplitude. The FEA results also showed that the vibrational amplitude holds a significant effect on the cutting heat conduction.
The optimal surgical technique for multilevel cervical degenerative disc diseases (DDD) remains controversial. Hybrid surgery (HS) incorporating anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) is increasingly performed for cervical DDD. This study aims to evaluate the biomechanical and clinical evidence available for HS and to provide a systematic review of current understanding of HS.
Although a human eye comprises less than 0.1% of the frontal body surface area, injuries to the eye are found to be disproportionally common in survivors of explosions. This study aimed to introduce a Lagrangian-Eulerian coupling model to predict globe rupture resulting from primary blast effect. A finite element model of a human eye was created using Lagrangian mesh. An explosive and its surrounding air domain were modelled using Eulerian mesh. Coupling the two models allowed simulating the blast wave generation, propagation and interaction with the eye. The results showed that the peak overpressures caused by blast wave on the corneal apex are 2080, 932.1 and 487.3 kPa for the victim distances of 0.75, 1.0 and 1.25 m, respectively. Higher stress occurred at the limbus, where the peaks for the three victim distances are 25.5, 14.1 and 6.4 MPa. The overpressure threshold of globe rupture was determined as 2000 kPa in a small-scale explosion. The findings would provide insights into the mechanism of primary blast-induced ocular injuries.
Burn wound dressings have played significant roles in daily clinical practice. An "ideal" burn wound dressing is non-adhesion, absorbency and antimicrobial activity. However, such a dressing is currently not available. A novel composite hydrogel was based on poly (vinyl alcohol) (PVA) containing lysine (Lys) and vanillin (V) using freezing-thawing method. The properties of this hydrogel were characterized by environmental scanning electron microscope (ESEM), attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR), tensile testing, differential scanning calorimetry (DSC) and water vapour transmission rate (WVTR). Then the antibacterial activity of PVA/Lys/V composite hydrogel was examined by bacteriolytic plate. In vivo experiment, a burn rat model was used to evaluate the histological analysis of this hydrogel. In results, the Schiff base formed in the three-phase system. It improved the tensile strength and crystallization of the PVA/Lys/V composite hydrogel. Meanwhile, this hydrogel showed excellent bactericidal activities to both gram-negative bacteria (E. coli) and gram-positive bacteria (S. aureus) due to the Schiff base. And the antibacterial activity toward gram-negative bacteria was better than another. On Day 7, 95-100% of the surface areas of PVA/Lys/V composite treated burns were covered with regenerating epidermis. And the new tissue and capillary vessel formed around the wounds after treatment. Therefore, it is suggested that treatment with PVA/Lys/V composite hydrogel will be effective also in patients with burns and other skin wounds.
A new approach for fabrication of a long-term and recoverable antimicrobial nanostructure/textile hybrid without increasing the antimicrobial resistance is demonstrated. Using in situ synthesized Ag nanoparticles (NPs) anchored on ZnO nanowires (NWs) grown on textiles by a 'dip-in and light-irradiation' green chemical method, we obtained ZnONW@AgNP nanocomposites with small-size and uniform Ag NPs, which have shown superior performance for antibacterial applications. These new Ag/ZnO/textile antimicrobial composites can be used for wound dressings and medical textiles for topical and prophylactic antibacterial treatments, point-of-use water treatment to improve the cleanliness of water and antimicrobial air filters to prevent bioaerosols accumulating in ventilation, heating, and air-conditioning systems.
It has been stated clearly that nanofillers could make an enhancement on the mechanical performances of dental composites. In order to address current shortage of traditional dental composites, fillers in forms of nanofibers or nanotubes are broadly regarded as ideal candidates to greatly increase mechanical performances of dental composites with low content of fillers. In this review, the efforts using nanofibers and nanotubes to reinforce mechanical performances of dental composites, including polymeric nanofibers, metallic nanofibers or nanotubes, and inorganic nanofibers or nanotubes, as well as their researches related, are demonstrated in sequence. The first purpose of current paper was to confirm the enhancement of nanofibers or nanotubes' reinforcement on the mechanical performances of dental restorative composite. The second purpose was to make a general description about the reinforcement mechanism of nanofibers and nanotubes, especially, the impact of formation of interphase boundary interaction and nanofibers themselves on the advanced mechanical behaviors of the dental composites. By means of the formation of interface interaction and poststretching nanofibers, reinforced effect of dental composites by sorts of nanofibers/nanotubes has been successfully obtained.
Although the mammalian IRE1?-XBP1 branch of the cellular unfolded protein response has been implicated in glucose and lipid metabolism, the exact metabolic role of IRE1? signalling in vivo remains poorly understood. Here we show that hepatic IRE1? functions as a nutrient sensor that regulates the metabolic adaptation to fasting. We find that prolonged deprivation of food or consumption of a ketogenic diet activates the IRE1?-XBP1 pathway in mouse livers. Hepatocyte-specific abrogation of Ire1? results in impairment of fatty acid ?-oxidation and ketogenesis in the liver under chronic fasting or ketogenic conditions, leading to hepatosteatosis; liver-specific restoration of XBP1s reverses the defects in IRE1? null mice. XBP1s directly binds to and activates the promoter of PPAR?, the master regulator of starvation responses. Hence, our results demonstrate that hepatic IRE1? promotes the adaptive shift of fuel utilization during starvation by stimulating mitochondrial ?-oxidation and ketogenesis through the XBP1s-PPAR? axis.
Toll-like receptors (TLRs) play an essential role in innate immune response. Expression of TLRs has also been linked to autophagy. As the main receptor for oxidized low-density lipoprotein (ox-LDL) on the cell surface, lectin-like ox-LDL receptor-1 (LOX-1) is upregulated by proinflammatory cytokines and has been linked to the development of autophagy. However, the relationship between LOX-1, autophagy, and TLR4 in neurons has not been defined. Here, we show that Angiotensin II (Ang II) treatment of CATH.a differentiated neuronal cells resulted in the expression of TLR4 (and associated signals MyD88 and Toll/interleukin-1 receptor domain-containing adapter-inducing interferon (TRIF)), LOX-1 autophagy. LOX-1 knockdown (transfection with specific small interfering RNA (siRNA)) resulted in reduced expression of TLR4 (and associated signals MyD88 and TRIF) and P-P38 mitogen-activated protein kinase (MAPK) and autophagy. TLR4 knockdown with siRNA resulted in reduced LOX-1 expression and autophagy, indicating a positive feedback between LOX-1 and TLR4. Knockdown of TRIF as well as MyD88 or inhibition of P38 MAPK also inhibited the expression of LOX-1 and TLR4 and autophagy. Importantly, pretreatment with 3-methyladenine (autophagy inhibitor) enhanced while rapamycin (autophagy inducer) decreased the expression of LOX-1, TLR4, and P-P38 MAPK. These studies suggest the presence of a bidirectional link between LOX-1and TLR4 in cultured CATH.a differentiated cells exposed to Ang II with an important role for autophagy in this link.
A series of novel di- and tripeptidyl epoxyketone derivatives composed of ?-amino acids were designed, synthesized and evaluated for their proteasome inhibitory activities and anti-proliferation activities against two multiple myeloma cell lines RPMI 8226 and NCI-H929 and normal cells (peripheral blood mononucleated cells). Among these tested compounds, tripeptidyl analogues showed much more potent activities than dipeptides, and four tripeptidyl compounds exhibited proteasome inhibitory activities with IC50 values ranging from 0.97 ± 0.05 to 1.85 ± 0.11 ?m. In addition, all the four compounds showed anti-proliferation activities with IC50 values at low micromolar levels against two multiple myeloma cell lines and weak activities against normal cells. Furthermore, Western blot analysis was performed to verify the proteasome inhibition induced by compounds 21d and 21e. All the experimental results validated that the ?-amino acid building block has the potential for the development of proteasome inhibitors.
A series of novel tripeptidyl epoxyketone derivatives constructed from ?-amino acid were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome inhibitory activities and selected compounds were tested for their anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and NCI-H929. Among them, eleven compounds exhibited proteasome inhibitory rates of more than 50% at the concentration of 1 ?g/mL and nine compounds showed anti-proliferation activities with IC50 values at low micromolar level. Compound 20h displayed the most potent proteasome inhibitory activities (IC50: 0.11 ± 0.01 ?M) and anti-proliferation activities with IC50 values at 0.23 ± 0.01 and 0.17 ± 0.02 ?M against two tested cell lines. Additionally, the poly-ubiquitin accumulation in the western blot analysis supported that proteasome inhibition in a cellular system was induced by compound 20h. All these experimental results confirmed that ?-amino acid can be introduced as a building block for the development of proteasome inhibitors.
A good knowledge of midfoot biomechanics is important in understanding the biomechanics of the entire foot, but it has never been investigated thoroughly in the literature. This study carried out in vitro experiments and finite element analysis to investigate the midfoot biomechanics. A foot-ankle finite element model simulating the mid-stance phase of the normal gait was developed and the model validated in in vitro experimental tests. Experiments used seven in vitro samples of fresh human cadavers. The simulation found that the first principal stress peaks of all midfoot bones occurred at the navicular bone and that the tensile force of the spring ligament was greater than that of any other ligament. The experiments showed that the longitudinal strain acting on the medial cuneiform bone was -26.2±10.8 ?-strain, and the navicular strain was -240.0±169.1 ?-strain along the longitudinal direction and 65.1±25.8 ?-strain along the transverse direction. The anatomical position and the spring ligament both result in higher shear stress in the navicular bone. The load from the ankle joint to five branches of the forefoot is redistributed among the cuneiforms and cuboid bones. Further studies on the mechanism of loading redistribution will be helpful in understanding the biomechanics of the entire foot.
Many studies have demonstrated that in vitro shear stress conditioning of endothelial cell-seeded small-diameter vascular grafts can improve cell retention and function. However, the laminar flow and pulsatile flow conditions which are commonly used in vascular tissue engineering and hemodynamic studies are quite different from the actual physiological pulsatile flow which is pulsatile in nature with typical pressure and flow waveforms. The actual physiological pulsatile flow leading to temporal and spatial variations of the wall shear stress may result in different phenotypes and functions of ECs. Thus, the aim of this study is to find out the best in vitro dynamic culture conditions to generate functional endothelium on sulfated silk fibroin nanofibrous scaffolds for small-diameter vascular tissue engineering. Rat aortic endothelial cells (RAECs) were seeded on sulfated silk fibroin nanofibrous scaffolds and cultured under three different patterns of flow conditioning, e.g., steady laminar flow (SLF), sinusoidal flow (SF), or physiological pulsatile flow (PPF) representative of a typical femoral distal pulse wave in vivo for up to 24 h. Cell morphology, cytoskeleton alignment, fibronectin assembly, apoptosis, and retention on the scaffolds were investigated and were compared between three different patterns of flow conditioning. The results showed that ECs responded differentially to different exposure time and different flow patterns. The actual PPF conditioning demonstrated excellent EC retention on sulfated silk fibroin scaffolds in comparison with SLF and SF, in addition to the alignment of cells in the direction of fluid flow, the formation of denser and regular F-actin microfilament bundles in the same direction, the assembly of thicker and highly crosslinked fibronectin, and the significant inhibition of cell apoptosis. Therefore, the actual PPF conditioning might contribute importantly to the generation of functional endothelium on a sulfated silk fibroin nanofibrous scaffold and thereby yield a thromboresistant luminal surface.
Mechano growth factor (MGF) and its C-terminal E-peptide with 24 amino acids, MGF-Ct24E, have superiority in resolving the delayed or failed bone repair derived from shortness of suitable biomechanical stimulation. The chitosan/tripolyphosphate microspheres encapsulated with MGF-Ct24E (CS/TPP/MGF-Ct24E) are prepared using emulsion-ionic cross-linking method in order to achieve the sustained release and preserve the bioactivity of MGF-Ct24E. The microspheres are micron-sized and spherical in shape with smooth surface morphology. The TPP component disintegrates in advance of CS matrix and the MGF-Ct24E maintains sustained delivery during in vitro hydrolytic degradation. With the disappearance of TPP, the total weight loss of CS/TPP/MGF-Ct24E is 32% and the release amount of MGF-Ct24E reaches 84.6% after degrading for 2 weeks. In vitro bioactivity assays reveal that the MGF-Ct24E can accelerate MC3T3-E1 cells proliferation and delay their differentiation as well. The encapsulated MGF-Ct24E shows long-term effects after being loaded in the CS/TPP microspheres and the cells exhibit excellent morphology on the surface of microspheres. The continuous delivery of MGF-Ct24E provides a new perspective on resolving the unsatisfactory bone reconstruction associated with microgravity and stress shielding.
The tibial drill-guide angle in anterior cruciate ligament (ACL) reconstruction influences the tunnel placement and graft-tunnel force, and is potentially associated with post-operative tunnel widening. This study aimed to examine the effect of the drill-guide angle on the stress redistribution at the tibial tunnel aperture after anatomic single-bundle ACL reconstruction.
Kneeling is a common activity required for both occupational and cultural reasons and has been shown to be associated with an increased risk of knee disorders. While excessive contact pressure is considered to be a possible aggressor, it is not clear whether and to what extent stress on the cartilage during kneeling is different from that while standing. In this study, finite element models of the knee joint for both kneeling and standing positions were constructed. The results indicated differences in high-stress regions between kneeling and standing. And both the peak von-Mises stress and contact pressure on the cartilage were larger in kneeling. During kneeling, the contact pressure reached 4.25 MPa under a 300 N compressive load. It then increased to 4.66 MPa at 600 N and 5.15 MPa at 1000 N. Changing the Poisson's ratio of the cartilage, which represents changes in compressibility caused by different loading rates, was found to have an influence on the magnitude of stress.
Studies on in vitro bioaccessibility and safety assessment of 6 elements namely Fe, Zn, Cu, Mn, As and Cd in decoction of eight commonly consumed "Zhebawei" herbal medicines were carried out. The method was based on simulation of human digestion in the gastrointestinal tract. Total content and content in extracts from gastrointestinal phases were analyzed for these elements by inductively coupled plasma atomic emission spectrometer (ICP-AES). In decoction of all 8 herbal medicines, it was found that the total content and bioaccessible concentration of these elements varied considerably among the types of herb, and the total content of each element did not show linearity with their bioaccessible content of the corresponding element. There is no risk of adverse health effects resulting from overdose of Fe, Zn, Cu, and Mn for almost all individuals by ingesting recommended maximum daily dose of these eight herbal medicines. In terms of Cd only Ophitopogin japonicum had higher total concentration and bioaccessible content than the value of suggested limit (5.4?g/d). For total As content, only Scrophularia ningpoensis and Corydalis yanhusuo did not meet the safety standard. However, regarding bioaccessible As contents, none of the eight herbal medicines exceeded the value of the daily permissible intake of As (0.12mg). The risk of toxicity from an element in herbal medicine might be overestimated when the total concentration but not the bioaccessible content is taken into account. In vitro digestion method is rapid, relatively simple and inexpensive, which could be helpful in conducting experiments about safety assessment of an element in herbal medicines.
Despite the crucial role of nitric oxide (NO) in the homeostasis of the vasculature, little quantitative information exists concerning NO transport and distribution in medium and large-sized arteries where atherosclerosis and aneurysm occur and hemodynamics is complex. We hypothesized that local hemodynamics in arteries may govern NO transport and affect the distribution of NO in the arteries, hence playing an important role in the localization of vascular diseases. To substantiate this hypothesis, we presented a lumen/wall model of the human aorta based on its MRI images to simulate the production, transport and consumption of NO in the arterial lumen and within the aortic wall. The results demonstrated that the distribution of NO in the aorta was quite uneven with remarkably reduced NO bioavailability in regions of disturbed flow, and local hemodynamics could affect NO distribution mainly via flow dependent NO production rate of endothelium. In addition, erythrocytes in the blood could moderately modulate NO concentration in the aorta, especially at the endothelial surface. However, the reaction of NO within the wall could only slightly affect NO concentration on the luminal surface, but strongly reduce NO concentration within the aortic wall. A strong positive correlation was revealed between wall shear stress and NO concentration, which was affected by local hemodynamics and NO reaction rate. In conclusion, the distribution of NO in the aorta may be determined by local hemodynamics and modulated differently by NO scavengers in the lumen and within the wall.
References to anatomical entities in medical records consist not only of explicit references to anatomical locations, but also other diverse types of expressions, such as specific diseases, clinical tests, clinical treatments, which constitute implicit references to anatomical entities. In order to identify these implicit anatomical entities, we propose a hierarchical framework, in which two layers of named entity recognizers (NERs) work in a cooperative manner. Each of the NERs is implemented using the Conditional Random Fields (CRF) model, which use a range of external resources to generate features. We constructed a dictionary of anatomical entity expressions by exploiting four existing resources, i.e., UMLS, MeSH, RadLex and BodyPart3D, and supplemented information from two external knowledge bases, i.e., Wikipedia and WordNet, to improve inference of anatomical entities from implicit expressions. Experiments conducted on 300 discharge summaries showed a micro-averaged performance of 0.8509 Precision, 0.7796 Recall and 0.8137 F1 for explicit anatomical entity recognition, and 0.8695 Precision, 0.6893 Recall and 0.7690 F1 for implicit anatomical entity recognition. The use of the hierarchical framework, which combines the recognition of named entities of various types (diseases, clinical tests, treatments) with information embedded in external knowledge bases, resulted in a 5.08% increment in F1. The resources constructed for this research will be made publicly available.
Fluorescence molecular tomography in the near-infrared region is becoming a powerful modality for mapping the three-dimensional quantitative distributions of fluorochromes in live small animals. However, wider application of fluorescence molecular tomography still requires more accurate and stable reconstruction tools. We propose a shape-based reconstruction method that uses spherical harmonics parameterization, where fluorophores are assumed to be distributed as piecewise constants inside disjointed subdomains and the remaining background. The inverse problem is then formulated as a constrained nonlinear least-squares problem with respect to shape parameters, which decreases ill-posedness because of the significantly reduced number of unknowns. Since different shape parameters contribute differently to the boundary measurements, a two-step and modified block coordinate descent optimization algorithm is introduced to stabilize the reconstruction. We first evaluated our method using numerical simulations under various conditions for the noise level and fluorescent background; it showed significant superiority over conventional voxel-based methods in terms of the spatial resolution, reconstruction accuracy with regard to the morphology and intensity, and robustness against the initial estimated distribution. In our phantom experiment, our method again showed better spatial resolution and more accurate intensity reconstruction. Finally, the results of an in vivo experiment demonstrated its applicability to the imaging of mice.
Cell migration is of vital importance in many biological processes, including organismal development, immune response and development of vascular diseases. For instance, migration of vascular smooth muscle cells from the media to intima is an essential part of the development of atherosclerosis and restenosis after stent deployment. While it is well characterized that cells use actin polymerization at the leading edge to propel themselves to move on two-dimensional substrates, the migration modes of cells in three-dimensional matrices relevant to in vivo environments remain unclear. Intracellular tension, which is created by myosin II activity, fulfils a vital role in regulating cell migration. We note that there is compelling evidence from theoretical and experimental work that myosin II accumulates at the cell rear, either isoform-dependent or -independent, leading to three-dimensional migration modes driven by posterior myosin II tension. The scenario is not limited to amoeboid migration, and it is also seen in mesenchymal migration in which a two-dimensional-like migration mode based on front protrusions is often expected, suggesting that there may exist universal underlying mechanisms. In this review, we aim to shed some light on how anisotropic myosin II localization induces cell motility in three-dimensional environments from a biomechanical view. We demonstrate an interesting mechanism where an interplay between mechanical myosin II recruitment and biochemical myosin II activation triggers directional migration in three-dimensional matrices. In the case of amoeboid three-dimensional migration, myosin II first accumulates at the cell rear to induce a slight polarization displayed as a uropod-like structure under the action of a tension-dependent mechanism. Subsequent biochemical signalling pathways initiate actomyosin contractility, producing traction forces on the adhesion system or creating prominent motile forces through blebbing activity, to drive cells to move. In mesenchymal three-dimensional migration, cells can also take advantage of the elastic properties of three-dimensional matrices to move. A minor myosin isoform, myosin IIB, is retained by relatively stiff three-dimensional matrices at the posterior side, then activated by signalling cascades, facilitating prominent cell polarization by establishing front-back polarity and creating cell rear. Myosin IIB initiates cell polarization and coordinates with the major isoform myosin IIA-assembled stress fibres, to power the directional migration of cells in the three-dimensional matrix.
Evidence from ground-based animal studies using tail-suspended hindlimb unloaded rats model has clearly demonstrated that simulated microgravity-induced smooth muscle cell phenotype conversion, a characteristic vascular structural and functional remodeling, may be one of the key contributors to postspaceflight orthostatic intolerance. However, the rats model involves multiple collective effects of microgravity including cephalic fluid shift and postural muscle unloading on smooth muscle cells (SMCs). It cannot isolate a single factor from the collective ones and therefore is not ideal to study the effects of gravitational vector alteration alone on SMCs. To test the hypothesis that gravitational vector alteration per se might affect smooth muscle cell phenotype, a roller culture apparatus was employed to expose cultured rat aortic smooth muscle cells (RASMCs) to simulated microgravity. Cell proliferation, cell cycle distribution, apoptosis, migration, and nitric oxide production rates were measured and compared between the control and the simulated microgravity groups. Cell cytoskeleton reorganization induced by simulated microgravity was observed by confocal microscopy. Specific contractile and synthetic Gene expression at the mRNA level was quantified by reverse transcriptional polymerase chain reaction. It was observed that simulated microgravity suppressed RASMC proliferation and migration, enhanced cell apoptosis, stimulated NO release, and destroyed the original well-organized cytoskeleton. Moreover, at the mRNA level, long-time exposure (? 72 h) to simulated microgravity induced a contractile phenotype tendency by up-regulating smMHC expression. All these findings suggest that the phenotype modulation of vascular smooth muscle cells may be gravity dependent.
Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the three-dimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.
A new type of signaling network element, called cancer signaling bridges (CSB), has been shown to have the potential for systematic and fast-tracked drug repositioning. On the basis of CSBs, we developed a computational model to derive specific downstream signaling pathways that reveal previously unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available patient gene expression data. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by the maximal number of enriched signaling pathways specific to a given metastasis, and (ii) CSB proteins are involved in the most differential expressed coding genes specific to each breast cancer metastasis. The identified signaling networks for the three types of breast cancer metastases contain 31, 15, and 18 proteins and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases. We conducted both in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Of special note, we found that the Food and Drug Administration-approved drugs, sunitinib and dasatinib, prohibit brain metastases derived from breast cancer, addressing one particularly challenging aspect of this disease.
Imidazolinylidene, imidazolylidine, benzimidazolylidene complexes 1a-c were prepared and tested in asymmetric hydrogenations of a series of largely unfunctionalized alkenes. Similarities and differences in the catalytic performance of these complexes were rationalized in terms of the predicted mechanisms of these reactions, and their relative tendencies to generate protons under the hydrogenation conditions.
Multivalency is a powerful strategy for achieving high-affinity molecular binding of compounds to increase their therapeutic potency or imaging potential. In our study, multivalent non-peptide integrin ?v?3 antagonists (IA) were designed for antitumor therapy. Docking and molecular dynamics were employed to explore the binding modes of IA monomer, dimer, and trimer. In silico, one IA unit binds tightly in the active site with similar pose to native ligand RGD and other parts of dimer and trimer contribute extra binding affinities by interacting with residues in vicinity of the original site. In vitro studies demonstrated that increasing valency results in increasing antiproliferative and antiorganizational effects against endothelial cells (HUVECs), and a much weaker effect on melanoma B16F10 cells. The antitumor efficacies of the IA multivalent compounds were evaluated in subcutaneous B16F10 melanoma tumor-bearing mice. At 30 mg/kg dose, the mean masses of tumors harvested 18 days after inoculation were significantly reduced (p<10(-7)) by 36±9%, 49±8%, and 71±7% for the IA monomer, dimer, and trimer groups, relative to control. The importance of multivalency was demonstrated to be highly significant beyond the additive effect of the extra pharmacological sites (p=0.00011). These results suggest that the major target of these anti-?v?3 compounds is the neovasculature rather than the cancer cells, and the success of a multivalent strategy depends on the details of the components and linker. This is the first integrin ?v?3 multivalent ligand showing clear enhancement in antitumor effectiveness.
Polypyrrole (PPy), as an electrical conductive polymer, has been widely investigated in biomedical fields. In this study, PPy membrane at nanoscale was electrically deposited on indium-tin oxide glass slide with sodium p-toluenesulfonate as supporting electrolyte. Electropolymerization of PPy was performed under a constant 800 mV voltage for 10 seconds. Chemical compositions and morphology were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The results showed that the nanoscaled PPy particles distributed uniformly and the average diameter of PPy particles was 62 nm. Since bone cells can respond to both electrical and mechanical stimulation in vivo, pre-osteoblasts MC3T3-E1 cells were cultured ort nanostructured PPy membrane under the combined electrical and mechanical stimulation. The nano-PPy membrane was conducive to transferring uniform electrical stimulation and applying steady mechanical stimulation. It is suggested that the combined stimulation did not affect cells morphologies significantly. However, cell proliferation tested by MTT, alkaline phosphatase activities, and gene expression of Collagen-I indicated that combined stimulation can enhance the proliferation and differentiation of MC3T3-E1 cells more efficiently than single electrical stimulation or single mechanical stimulation. The combined stimulation through a nano-PPy membrane may provide a highly potential stimulated method in bone tissue engineering.
Stem cell therapy may provide a therapeutic method for the replacement and regeneration of damaged neurons of the central nervous system. However, neural stem cells (NSCs) and neural precursor cells (NPCs) are especially vulnerable after transplantation due to a lack of sufficient growth factors at the transplant site. Electrical stimulation (ES) has recently been found to participate in the regulation of cell proliferation, growth, differentiation, and migration, but its underlying anti-apoptotic effects remain unclear. This study investigated the protective effects of biphasic electrical stimulation (BES) on olfactory bulb NPCs against growth factor-deprived apoptosis, examining the survival and apoptotic features of the cells. Differentiation was assessed by neuronal and glial markers. Brain-derived neurotrophic factor-phosphatidylinositol 3-kinase (BDNF)-PI3K/Akt pathway activation was determined by enzyme-linked immunosorbent assay and Western blot. The chemical inhibitor wortmannin was used to inhibit the PI3K/Akt pathway. BES exerts a protective effect against growth factor-deprived apoptosis in the NPCs. BES enhanced cell survival and decreased the apoptotic/necrotic rate. Expression of phosphorylated Akt and BDNF secretion increased with BES for 12?h. Furthermore, the protective effects of BES were inhibited by blocking PI3K/AKT signalling. These results suggest that BES prevents growth factor-deprived apoptosis through the BDNF-PI3K/Akt signalling. This work strengthens the opinion that BES may be used as an auxiliary strategy for improving cell survival and preventing cell apoptosis in stem cell-based transplantation therapy.
In this paper, we focus on three aspects: (1) to annotate a set of standard corpus in Chinese discharge summaries; (2) to perform word segmentation and named entity recognition in the above corpus; (3) to build a joint model that performs word segmentation and named entity recognition.
Colon cancer classification has a significant guidance value in clinical diagnoses and medical prognoses. The classification of colon cancers with high accuracy is the premise of efficient treatment. Our task is to build a system for colon cancer detection and classification based on slide histopathological images. Some former researches focus on single label classification. Through analyzing large amount of colon cancer images, we found that one image may contain cancer regions of multiple types. Therefore, we reformulated the task as multi-label problem. Four kinds of features (Color Histogram, Gray-Level Co-occurrence Matrix, Histogram of Oriented Gradients and Euler number) were introduced to compose our discriminative feature set, extracted from our dataset that includes six single categories and four multi-label categories. In order to evaluate the performance and make comparison with our multi-label model, three commonly used multi-classification methods were designed in our experiment including one-against-all SVM (OAA), one-against-one SVM (OAO) and multi-structure SVM. Four indicators (Precision, Recall, F-measure, and Accuracy) under 3-fold cross-validation were used to validate the performance of our approach. Experiment results show that the precision, recall and F-measure of multi-label method as 73.7%, 68.2%, and 70.8% with all features, which are higher than the other three classifiers. These results demonstrate the effectiveness and efficiency of our method on colon histopathological images analysis.
Owing to the high risk of abscess drainage by craniotomy, imaging-guided stereotactic aspiration is considered an ideal choice in the management of brain abscesses. Interventional magnetic resonance imaging (MRI) represents a valuable technique for the treatment of brain abscess as a guiding modality.
The prevalence of osteoarthritis of the atlanto-odontoid joint has been reported by radiology, autopsy, and conventional computed tomography (CT), but the prevalence has not yet been assessed by multidetector computed tomography (MDCT).
Nanoscale materials (such as TiO2, hydroxyapatite nanoparticles) have gained much concern in the coating of implants for cell adhesion and growth to improve the osteoconductivity. However, due to attrition and corrosion, the wear particles would be generated from the joint in living organism, and influence the physiological function of synovial membranes in joint cavity. In this study, the potential cytotoxicity of anatase TiO2 nanoparticles (TiO2 NPs) on rat synovial cell line 364 (RSC-364) was investigated. After treatment with different concentrations of TiO2 NPs (0, 3, 30, 300 microg/ml), the viability of RSC-364 cells were decreased in a dose-dependent manner. TiO2 NPs exposure could disrupt the integrity of cell plasma membrane, leading to the increased leakage of lactate dehydrogenase (LDH) into the culture medium. TiO2 NPs were uptaken by RSC-364 cells. The ultrastructure of RSC-364 cells was changed such as nuclear shrinkage and mitochondrial swelling. The reactive oxygen species (ROS) was over-produced especially in the cells exposed to 30 and 300 microg/ml TiO2 NPs. The activities of endogeneous antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were significantly decreased. The increased lipid peroxidation product (malondialdehyde, MDA) suggests the oxidative damage in cells. The flow cytometry detected that the cell cycle was blocked in G0/G1 phase, inhibiting the cell proliferation. These preliminary results indicate the oxidative stress injury and cytotoxicity of anatase TiO2 NPs on rat synovial cells. The reasonable and safe application of nanomaterials in artificial implants needs further study.
Previously, we have shown that vascular smooth muscle cells (VSMCs) exhibit varied physiological responses when exposed to altered gravitational conditions. In the present study, we focused on elucidating whether the cell surface glycocalyx could be a potential gravity sensor. For this purpose, a roller culture apparatus was used with the intent to provide altered gravitational conditions to cultured rat aortic smooth muscle cells (RASMCs). Heparinase III (Hep.III) was applied to degrade cell surface heparan sulfate proteoglycans (HSPG) selectively. Sodium chlorate was used to suppress new synthesis of HSPG. Glycocalyx remodeling, nitric oxide synthase (NOS) activation, and F-actin expression induced by gravity alteration were assessed by flow cytometry, reverse transcription polymerase chain reaction (RT-PCR), and Western blot. Results indicate that the exposure of cultured RASMCs to altered gravitational conditions led to a reduction in cell surface HSPG content and the activation of NOS. It also down-regulated the expression of glypican-1, constitutive NOS (NOSI and NOSIII), and F-actin. On the other hand, Hep.III followed by sodium chlorate treatment of HSPG attenuated the aforementioned NOS and F-actin modulation under altered gravitational conditions. All these findings suggest that the glycocalyx, and HSPG in particular, may be an important sensor of gravitational changes. This may play an important role in the regulation of NOS activation, F-actin modulation, and HSPG remodeling in VSMCs.
The current study aims to evaluate and compare the bony biomechanical response and possible long-term restorative consequences stemming from the use of two-unit fixed partial dentures (FPDs) with or without cantilever configuration. The numerical simulations of bone remodeling were performed using an adaptive strain energy density algorithm, which incorporates an overloading bone resorption process. A patient specific 3D finite element model of a maxillary bone with two absent central incisors was constructed on the basis of clinical computed tomography data. Two different implant-supported two-unit FPD models were developed. The simulated remodeling results were visualized by examining the variation of apparent bone density. Different bone responses under normal and overload conditions were compared quantitatively and qualitatively between the cantilever and non-cantilever models. The mechanical stress/strain distributions were also examined. Furthermore, the simulation results were compared with a similar clinical X-ray image of the implant site. This study revealed that bone resorption due to overloading was more severe in the cortical neck around the implant-supported cantilever FPD, as compared with the non-cantilever configuration, which is better for maintaining the overall health of bone tissue. It is expected that such simulation methodology can be helpful in improving longevity and reliability of future dental implants.
Three-dimensional (3D) morphometric analysis of cellular and subcellular structures provides an effective method for spatial cell biology. Here, 3D cellular and nuclear morphologies are reconstructed to quantify and compare morphometric differences between normal and apoptotic endothelial cells. Human umbilical vein endothelial cells (HUVECs) are treated with 60 ?M H2 O2 to get apoptotic cell model and then a series of sectional images are acquired from laser scanning confocal microscopy. The 3D cell model containing plasma membrane and cell nucleus is reconstructed and fused utilizing three sequential softwares or packages (Mimics, Geomagic, and VTK). The results reveal that H2 O2 can induce apoptosis effectively by regulating the activity of apoptosis-related biomolecules, including pro-apoptotic factors p53 and Bax, and anti-apoptotic factor Bcl-2. Compared with the normal HUVECs, the apoptotic cells exhibit significant 3D morphometric parameters (height, volume and nucleus-to-cytoplasm ratio) variation. The present research provides a new perspective on comparative quantitative analysis associated with cell apoptosis and points to the value of LSCM as an objective tool for 3D cell reconstruction.
We hypothesize that after implantation the much elevated water filtration rate of venous grafts may cause aggravated concentration polarization of low density lipoproteins (LDLs), in turn lead to the accelerated atherogenesis of the grafts. To verify the hypothesis, we numerically simulated the transport of LDLs in various models of arterial bypasses with different grafts (veins or arteries) and geometrical configurations. The results showed that the venous grafts might endure abnormally high lipid infiltration/accumulation within the vessel wall due to severely elevated luminal surface LDL concentration. When compared to the conventional bypass models, the S-type bypass had the lowest luminal surface LDL concentration along its host artery floor, but the highest degree of risk to develop atherosclerotic lesions in its venous graft. Among the three conventional bypass models, the one with 30° anastomosis had the lowest risk to develop atherosclerosis in the venous graft. In conclusion, when compared with the bypass models with arterial grafts, the venous bypass models had rather high levels of LDL concentration polarization (cw) in the vein grafts, especially at the early stages of implantation. This might result in high infiltration/accumulation of LDLs within the walls of the venous grafts, leading to a fast genesis/development of atherosclerosis there.
In view of the shortage of medical equipment road transportation simulation platform, we put forward a road transportation simulation method based on 6-DOF parallel robots. A 3D road spectrum model was built by the improvement of the harmonic superposition method. The simulation model was then compared with the standard model to verify its performance. Taking the road spectrum as the excitation, we could get the robot motion data to control the parallel robot through the S-shaped linear interpolation of the absolute position. It can simulate the movement of vehicles with different speed under various road conditions efficiently and accurately.
The urgent needs of functional arterial replacements for curing the vascular system diseases have been proposed for many years. However, an ideal small-diameter vascular scaffold, which is nonthrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of natural vessels, and supports neovascular tissue reconstruction, is still in progress. For this purpose, we previously attempted dual-delivery of VEGF and PDGF by double-layered electrospun membranes. Here, a multilayered vascular scaffold in 1.5-mm diameter with sufficient mechanical properties was developed by electrospinning from poly(ethylene glycol)-b-poly(L-lactide-co-?-caprolactone) (PELCL), poly(L-lactide-co-glycolide) (PLGA), poly(?-caprolactone) (PCL) and gelatin. Spatio-temporal releases of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGF) were specially controlled by the inner PELCL and middle PLGA layers, respectively, and the outer PCL layer contributed to the mechanical stability. Introduction of gelatin improved vascular endothelial cells adhesion at first, and loosen membrane after its degradation facilitated vascular smooth muscle cells (VSMCs) ingrowth. Cell activities indicated dual release of growth factors promoted endothelialization and inhibited VSMCs hyperproliferation. The small-diameter vascular scaffold dual-loading VEGF and PDGF could maintain patency in rabbit left common carotid artery for 8 weeks. It is concluded that the specially prepared fibrous scaffold in multilayer could benefit blood vessel reconstruction.
A series of 7-azaindazolyl-indolyl-maleimides were designed, synthesized and evaluated for their GSK-3? inhibitory activity. Most compounds exhibited potent activity against GSK-3?. Among them, compounds 17a, 17b, 17g, 17i, 29a and 30 significantly reduced A?-induced Tau hyperphosphorylation, showin;g the inhibition of GSK-3? at the cell level. Preliminary structure-activity relationships were discussed based on the experimental data obtained.
A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3? inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3?. Among them, compound 7j with an IC?? value of 0.73 nM was the most promising GSK-3? inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N¹-position of the indole ring had varying degrees of influence on the GSK-3? inhibitory potency. Compounds 7c, 7f, 7j-l and 7o-q could obviously reduce A?-induced Tau hyperphosphorylation by inhibiting GSK-3? in a cell-based functional assay.
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.