Histotripsy and Catheter-Directed Lytic: Efficacy in Highly Retracted Porcine Clots In Vitro.

OBJECTIVE: Standard treatment for deep vein thrombosis (DVT) involves catheter-directed anticoagulants or thrombolytics, but the chronic thrombi present in many DVT cases are often resistant to this therapy. Histotripsy has been found to be a promising adjuvant treatment, using the mechanical action of cavitating bubble clouds to enhance thrombolytic activity. The objective of this study was to determine if histotripsy enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis in highly retracted porcine clots in vitro in a flow model of occlusive DVT. METHODS: Highly retracted porcine whole blood clots were treated for 1 h with either catheter-directed saline (negative control), rt-PA (lytic control), histotripsy, DEFINITY and histotripsy or the combination of rt-PA and histotripsy with or without DEFINITY. Five-cycle, 1.5 MHz histotripsy pulses with a peak negative pressure of 33.2 MPa and pulse repetition frequency of 40 Hz were applied along the clot. B-Mode and passive cavitation images were acquired during histotripsy insonation to monitor bubble activity. RESULTS: Clots subjected to histotripsy with and without rt-PA exhibited greater thrombolytic efficacy than controls (7.0% flow recovery or lower), and histotripsy with rt-PA was more efficacious than histotripsy with saline (86.1 ± 10.2% compared with 61.7 ± 19.8% flow recovery). The addition of DEFINITY to histotripsy with or without rt-PA did not enhance either thrombolytic efficacy or cavitation dose. Cavitation dose generally did not correlate with thrombolytic efficacy. CONCLUSION: Enhancement of thrombolytic efficacy was achieved using histotripsy, with and without catheter-directed rt-PA, in the presence of physiologic flow. This suggests these treatments may be effective as therapy for DVT.

Ankle and hindfoot motion of healthy adults during running revealed by dynamic biplane radiography: Side-to-side symmetry, sex-specific differences, and comparison with walking.

This study aimed to characterize ankle and hindfoot kinematics of healthy men and women during overground running using biplane radiography, and to compare these data to those previously obtained in the same cohort during overground walking. Participants ran across an elevated platform at a self-selected pace while synchronized biplane radiographs of their ankle and hindfoot were acquired. Motion of the tibia, talus, and calcaneus was tracked using a validated volumetric model-based tracking process. Tibiotalar and subtalar 6DOF kinematics were obtained. Absolute side-to-side differences in ROM and kinematics waveforms were calculated. Side-to-side and sex-specific differences were evaluated at 10 % increments of stance phase with mixed model analysis. Pearson correlation coefficients were used to assess the relationship between stance-phase running and walking kinematics. 20 participants comprised the study cohort (10 men, mean age 30.8 ± 6.3 years, mean BMI 24.1 ± 3.1). Average absolute side-to-side differences in running kinematics waveforms were 5.6°/2.0 mm or less at the tibiotalar joint and 5.2°/3.2 mm or less at the subtalar joint. No differences in running kinematics waveforms between sides or between men and women were detected. Correlations were stronger at the tibiotalar joint (42/66 [64 %] of correlations were p < 0.05), than at the tibiotalar joint (38/66 [58 %] of correlations were p < 0.05). These results provide a normative reference for evaluating native ankle and hindfoot kinematics which may be informative in surgical or rehabilitation contexts. Sex-specific differences in ankle kinematics during overground running are likely not clinically or etiologically significant. Associations seen between walking and running kinematics suggest one could be used to predict the other.

Ankle and subtalar joint axes of rotation and center of rotation during walking and running in healthy individuals measured using dynamic biplane radiography.

The goal of this study was to determine how foot type and activity level affect ankle and hindfoot motion. Dynamic biplane radiography and a validated volumetric registration process was used to measure ankle and hindfoot motion of 20 healthy adults during walking and running. The helical axes of motion (HAM) during stance were calculated at the tibiotalar and subtalar joints. The intersection of each HAM and the rotation plane of interest defined the tibiotalar and subtalar centers of rotation (COR). Correlations between foot type and hindfoot kinematics were calculated using Pearson's correlations. The effect of activity, phase of gait, and dominant vs. non-dominant limb on HAM and COR were evaluated using linear mixed effects models. Activity and phase of gait influenced the superior location of the tibiotalar (p < 0.041) and subtalar (p < 0.044) CORs. Activity and gait phase affected tibiotalar (p < 0.049) and subtalar (p < 0.044) HAM direction during gait. Both HAM orientation and COR location changed with activity and phase of gait. These ankle and hindfoot kinematics have implications for total ankle replacement design and musculoskeletal models that estimate force and moment generating capabilities of muscles.

Controlled Synthesis and Enhanced Gas Sensing Performance of Zinc-Doped Indium Oxide Nanowires.

Indium oxide (In2O3) is a widely used n-type semiconductor for detection of pollutant gases; however, its gas selectivity and sensitivity have been suboptimal in previous studies. In this work, zinc-doped indium oxide nanowires with appropriate morphologies and high crystallinity were synthesized using chemical vapor deposition (CVD). An accurate method for electrical measurement was attained using a single nanowire microdevice, showing that electrical resistivity increased after doping with zinc. This is attributed to the lower valence of the dopant, which acts as an acceptor, leading to the decrease in electrical conductivity. X-ray photoelectron spectroscopy (XPS) analysis confirms the increased oxygen vacancies due to doping a suitable number of atoms, which altered oxygen adsorption on the nanowires and contributed to improved gas sensing performance. The sensing performance was evaluated using reducing gases, including carbon monoxide, acetone, and ethanol. Overall, the response of the doped nanowires was found to be higher than that of undoped nanowires at a low concentration (5 ppm) and low operating temperatures. At 300 °C, the gas sensing response of zinc-doped In2O3 nanowires was 13 times higher than that of undoped In2O3 nanowires. The study concludes that higher zinc doping concentration in In2O3 nanowires improves gas sensing properties by increasing oxygen vacancies after doping and enhancing gas molecule adsorption. With better response to reducing gases, zinc-doped In2O3 nanowires will be applicable in environmental detection and life science.

Synthesis and Physical Characteristics of Undoped and Potassium-Doped Cubic Tungsten Trioxide Nanowires through Thermal Evaporation.

We report an efficient method to synthesize undoped and K-doped rare cubic tungsten trioxide nanowires through the thermal evaporation of WO3 powder without a catalyst. The WO3 nanowires are reproducible and stable with a low-cost growth process. The thermal evaporation processing was conducted in a three-zone horizontal tube furnace over a temperature range of 550-850 °C, where multiple substrates were placed at different temperature zones. The processing parameters, including pressure, temperature, type of gas, and flow rate, were varied and studied in terms of their influence on the morphology, aspect ratio and density of the nanowires. The morphologies of the products were observed with scanning electron microscopy. High resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction studies were conducted to further identify the chemical composition, crystal structure and growth direction of the nanostructures. Additionally, the growth mechanism has been proposed. Furthermore, we investigated the potassium doping effect on the physical properties of the nanostructures. Photoluminescence measurements show that there were shorter emission bands at 360 nm and 410 nm. Field emission measurements show that the doping effect significantly reduced the turn-on electric field and increased the enhancement factor. Furthermore, as compared with related previous research, the K-doped WO3 nanowires synthesized in this study exhibited excellent field emission properties, including a superior field enhancement factor and turn-on electric field. The study reveals the potential of WO3 nanowires in promising applications for sensors, field emitters and light-emitting diodes.

Fabrication and Photocatalytic Properties of Zinc Tin Oxide Nanowires Decorated with Silver Nanoparticles.

With the continuous advancement of high-tech industries, how to properly handle pollutants has become urgent. Photocatalysis is a solution that may effectively degrade pollutants into harmless molecules. In this study, we synthesized single crystalline Zn2SnO4 (ZTO) nanowires through chemical vapor deposition and selective etching. The chemical bath redox method was used to modify the ZTO nanowires with Ag nanoparticles to explore the photocatalytic properties of the nanoheterostructures. The combination of the materials here is rare. Optical measurements by photoluminescence (PL) and UV-Vis show that the PL spectrum of ZTO nanowires was mainly in the visible light region and attributed to oxygen vacancies. The luminescence intensity of the nanowires was significantly reduced after modification, demonstrating that the heterojunction could effectively reduce the electron-hole pair recombination. The reduction increased with the increase in Ag decoration. The conversion from the UV-Vis absorption spectrum to the Tauc Plot shows that the band gap of the nanowire was 4.05 eV. With 10 ppm methylene blue (MB) as the degradation solution, ZTO nanowires exhibit excellent photodegradation efficiency. Reusability and stability in photodegradation of the nanowires were demonstrated. Photocatalytic efficiency increases with the number of Ag nanoparticles. The main reaction mechanism was confirmed by photocatalytic inhibitors. This study enriches our understanding of ZTO-based nanostructures and facilitates their applications in water splitting, sewage treatment and air purification.

Chemical Vapor Deposition-Fabricated Manganese-Doped and Potassium-Doped Hexagonal Tungsten Trioxide Nanowires with Enhanced Gas Sensing and Photocatalytic Properties.

Owing to its unique and variable lattice structure and stoichiometric ratio, tungsten oxide is suitable for material modification; for example, doping is expected to improve its catalytic properties. However, most of the doping experiments are conducted by hydrothermal or multi-step synthesis, which is not only time-consuming but also prone to solvent contamination, having little room for mass production. Here, without a catalyst, we report the formation of high-crystallinity manganese-doped and potassium-doped tungsten oxide nanowires through chemical vapor deposition (CVD) with interesting characterization, photocatalytic, and gas sensing properties. The structure and composition of the nanowires were characterized by transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDS), respectively, while the morphology and chemical valence were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively. Electrical measurements showed that the single nanowires doped with manganese and potassium had resistivities of 1.81 × 0-5 Ω·m and 1.93 × 10-5 Ω·m, respectively. The doping contributed to the phase transition from monoclinic to metastable hexagonal for the tungsten oxide nanowires, the structure of which is known for its hexagonal electron channels. The hexagonal structure provided efficient charge transfer and enhanced the catalytic efficiency of the tungsten oxide nanowires, resulting in a catalytic efficiency of 98.5% for the manganese-doped tungsten oxide nanowires and 97.73% for the potassium-doped tungsten oxide nanowires after four hours of degradation of methylene blue. Additionally, the gas sensing response for 20 ppm of ethanol showed a positive dependence of doping with the manganese-doped and potassium-doped responses being 14.4% and 29.7%, respectively, higher than the pure response at 250 °C. The manganese-doped and potassium-doped tungsten oxide nanowires are attractive candidates in gas sensing, photocatalytic, and energy storage applications, including water splitting, photochromism, and rechargeable batteries.

Synthesis and Characterization of Indium Tin Oxide Nanowires with Surface Modification of Silver Nanoparticles by Electrochemical Method.

In this study, indium tin oxide nanowires (ITO NWs) with high density and crystallinity were synthesized by chemical vapor deposition (CVD) via a vapor-liquid-solid (VLS) route; the NWs were decorated with 1 at% and 3 at% silver nanoparticles on the surface by a unique electrochemical method. The ITO NWs possessed great morphologies with lengths of 5~10 µm and an average diameter of 58.1 nm. Characterization was conducted through transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and X-ray photoelectron spectroscope (XPS) to identify the structure and composition of the ITO NWs. The room temperature photoluminescence (PL) studies show that the ITO NWs were of visible light-emitting properties, and there were a large number of oxygen vacancies on the surface. The successful modification of Ag was confirmed by TEM, XRD and XPS. PL analysis reveals that there was an extra Ag signal at around 1.895 eV, indicating the potential application of Ag-ITO NWs as nanoscale optical materials. Electrical measurements show that more Ag nanoparticles on the surface of ITO NWs contributed to higher resistivity, demonstrating the change in the electron transmission channel of the Ag-ITO NWs. ITO NWs and Ag-ITO NWs are expected to enhance the performance of electronic and optoelectronic devices.

Residual limb shear strain during gait is correlated with patient reported outcomes for persons with transfemoral amputation.

The purpose of this study was to measure residual limb skin strain and strain rate within the socket during gait in individuals with a transfemoral amputation and to determine if skin strain during gait is related to patient-reported comfort and function. It was hypothesized that greater skin strain and skin strain rate would correlate to worse patient-reported outcomes. It was also hypothesized that skin strain would progressively increase from the distal to the proximal end of the residuum and maximum strain would occur shortly after heel strike. Dynamic biplane radiography (DBR), combined with conventional motion capture, was used to measure skin deformation within the socket during treadmill walking for 10 persons with unilateral transfemoral amputation. The questionnaire for persons with a transfemoral amputation (Q-TFA) was administered to assess prosthetic use, mobility, health problems, and global health. Q-TFA Prosthetic Use score and Problem score were negatively correlated with the peak shear strains in the proximal and distal regions of the residuum, respectively. Maximum shear strain increased progressively from proximal to distal regions of the residual limb. Within-subject variability in shear strain waveforms during gait was 0.7% or less, but between-subject variability was 3.3% to 5.0% shear. This study demonstrates that skin shear within the socket of persons with transfemoral amputation can be measured during gait using DBR and the results suggest that greater skin shear in the proximal region of the socket is related to decreased prosthetic use.

Characterization of the complete mitochondrial genome of the Qiaoke sheep (Ovis aries).

Qiaoke sheep (Ovis aries) is a local sheep breed in Gansu province, China. It is a kind of Tibetan sheep that used for both meat and wool after long-term breeding. In this paper, the complete mitochondrial genome of Qiaoke sheep was sequenced. The total length of the mitochondrial genome is 16616 bp, and the base composition is 33.65% A, 13.14% G, 25.88% C and 27.33% T. The genome has a total of 37 genes, including 13 protein-coding genes, 22 tRNA genes, two ribosomal RNA genes and a control region (D-loop region). This complete sequence would enlarge useful genomic information for further studies.

Healthy ankle and hindfoot kinematics during gait: Sex differences, asymmetry and coupled motion revealed through dynamic biplane radiography.

The aims of this study were to compare male versus female and dominant versus non-dominant kinematics in the ankle and hindfoot, and to characterize coupled motion between the subtalar and tibiotalar joints during the support phase of gait. Twenty healthy adults walked on a laboratory walkway while synchronized biplane radiographs of the ankle and hindfoot were collected at 100 frames/s. A validated tracking technique was used to measure tibiotalar and subtalar kinematics. Differences between male and female range of motion (ROM) were observed only in tibiotalar (AP and ML) and subtalar (ML) translation (all differences<1 mm and all p < 0.04). Statistical parametric mapping identified differences between kinematics waveforms of males and females in tibiotalar translation (AP and ML) and eversion, and subtalar ML translation. No differences between dominant and non-dominant sides were observed in ROM or kinematics waveforms. The average absolute side-to-side difference in the kinematics waveforms was 4.1° and 1.5 mm or less for all rotations and translations, respectively. Tibiotalar plantarflexion was coupled to subtalar inversion and eversion during the impact and push-off phases of stance (r = 0.90 and r = 0.87, respectively). This data may serve as a guide for evaluating ankle kinematics waveforms, ROM, symmetry, and restoration of healthy coupled motion after surgical intervention or rehabilitation. The observed kinematics differences between males and females may predispose females to higher rates of ankle and knee injury and suggest sex-dependent ankle reconstruction techniques may be beneficial.

Motion of the residual femur within the socket during gait is associated with patient-reported problems in transfemoral amputees.

The purpose of this study was to provide a quantitative description of residual femur motion within the socket during gait and to explore the relationship between residual femur motion and patient-reported comfort and function. It was hypothesized that increased residual bone movement would correlate to worse patient-reported comfort and function. The secondary goals were to assess within-subject step-to-step variability and between-subject variability in residual femur motion within the socket during gait. Dynamic biplane radiography, combined with conventional motion capture, was used to measure residual femur motion within the socket during treadmill walking for 10 unilateral transfemoral amputees. The questionnaire for persons with a transfemoral amputation (Q-TFA) was administered to assess prosthetic use, mobility, health problems, and global health. Increased femur pistoning (proximal-distal translation relative to the socket) correlated with worsening Q-TFA problem and global scores (ρ = 0.741, p = 0.04 and ρ = -0.783, p = 0.02, respectively). Average residual femur rotation ROMs were 7.3°±3.7°, 10.8°±4.4°, and 7.7°±4.8° for anterior tilt, internal-external rotation, and varus-valgus, respectively. Average residual femur translation ROMs were 8.6 mm ± 3.0 mm, 28.4 mm ± 13.9 mm, and 20.4 mm ± 7.2 mm for medial-lateral, pistoning, and anterior-posterior directions, respectively. Within-subject rotational and translational variability during gait averaged 2.8° and 2.0 mm or less, whereas the between-subject variability was up to 9.4° and 18.6 mm, which demonstrates residual femur motion relative to the socket is repeatable within subjects, but inconsistent across subjects during gait. The results suggest residual bone motion within the socket is a potential mechanism behind patient-reported problems and suggests a target for intervention aimed at improving transfemoral amputee quality of life.

Fabrication and Physical Properties of Single-Crystalline Βeta-FeSi2 Nanowires.

In this study, self-catalyzed ß-FeSi2 nanowires, having been wanted but seldom achieved in a furnace, were synthesized via chemical vapor deposition method where the fabrication of ß-FeSi2 nanowires occurred on Si (100) substrates through the decomposition of the single-source precursor of anhydrous FeCl3 powders at 750-950 °C. We carefully varied temperatures, duration time, and the flow rates of carrier gases to control and investigate the growth of the nanowires. The morphology of the ß-FeSi2 nanowires was observed with scanning electron microscopy (SEM), while the structure of them was analyzed with X-ray diffraction (XRD) and transmission electron microscopy (TEM). The growth mechanism has been proposed and the physical properties of the iron disilicide nanowires were measured as well. In terms of the magnetization of ß-FeSi2, nanowires were found to be different from bulk and thin film; additionally, longer ß-FeSi2 nanowires possessed better magnetic properties, showing the room-temperature ferromagnetic behavior. Field emission measurements demonstrate that ß-FeSi2 nanowires can be applied in field emitters.

Synthesis of High-Density Indium Oxide Nanowires with Low Electrical Resistivity.

In this study, indium oxide nanowires of high-density were synthesized by chemical vapor deposition (CVD) through a vapor-liquid-solid (VLS) mechanism without carrier gas. The indium oxide nanowires possess great morphology with an aspect ratio of over 400 and an average diameter of 50 nm; the length of the nanowires could be over 30 µm, confirmed by field-emission scanning electron microscopy (SEM). Characterization was conducted with X-ray diffraction (XRD), transmission electron microscopy (TEM), photoluminescence spectrum (PL). High-resolution TEM studies confirm that the grown nanowires were single crystalline c-In2O3 nanowires of body-centered cubic structures. The room temperature PL spectrum shows a strong peak around 2.22 eV, originating from the defects in the crystal structure. The electrical resistivity of a single indium oxide nanowire was measured to be 1.0 × 10-4 Ω⋅cm, relatively low as compared with previous works, which may result from the abundant oxygen vacancies in the nanowires, acting as unintentional doping.

Single Crystalline Higher Manganese Silicide Nanowire Arrays with Outstanding Physical Properties through Double Tube Chemical Vapor Deposition.

In this work, we report a novel and efficient silicidation method to synthesize higher manganese silicide (HMS) nanowires with interesting characterization and physical properties. High density silicon nanowire arrays fabricated by chemical etching reacted with MnCl2 precursor through a unique double tube chemical vapor deposition (CVD) system, where we could enhance the vapor pressure of the precursor and provide stable Mn vapor with a sealing effect. It is crucial that the method enables the efficient formation of high quality higher manganese silicide nanowires without a change in morphology and aspect ratio during the process. X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to characterize the HMS nanowires. High-resolution TEM studies confirm that the HMS nanowires were single crystalline Mn27Si47 nanowires of Nowotny Chimney Ladder crystal structures. Magnetic property measurements show that the Mn27Si47 nanowire arrays were ferromagnetic at room temperature with a Curie temperature of over 300 K, highly depending on the relationship between the direction of the applied electric field and the axial direction of the standing nanowire arrays. Field emission measurements indicate that the 20 µm long nanowires possessed a field enhancement factor of 3307. The excellent physical properties of the HMS nanowires (NWs) make them attractive choices for applications in spintronic devices and field emitters.

Synthesis and Photocatalytic Properties of CuO-CuS Core-Shell Nanowires.

In this study, an efficient method to synthesize CuO-CuS core-shell nanowires by two-step annealing process was reported. CuO nanowires were prepared on copper foil via thermal oxidation in a three-zone horizontal tube furnace. To obtain larger surface area for photocatalytic applications, we varied four processing parameters, finding that growth at 550 °C for 3 h with 16 °C/min of the ramping rate under air condition led to CuO nanowires of appropriate aspect ratio and number density. The second step, sulfurization process, was conducted to synthesize CuO-CuS core-shell nanowires by annealing with sulfur powder at 250 °C for 30 min under lower pressure. High-resolution transmission electron microscopy studies show that a 10 nm thick CuS shell formed and the growth mechanism of the nanowire heterostructure has been proposed. With BET, the surface area was measured to be 135.24 m²·g-1. The photocatalytic properties were evaluated by the degradation of methylene blue (MB) under visible light irradiation. As we compared CuO-CuS core-shell nanowires with CuO nanowires, the 4-hour degradation rate was enhanced from 67% to 89%. This could be attributed to more effective separation of photoinduced electron and hole pairs in the CuO-CuS heterostructure. The results demonstrated CuO-CuS core-shell nanowires as a promising photocatalyst for dye degradation in polluted water.

Unloader knee brace increases medial compartment joint space during gait in knee osteoarthritis patients.

PURPOSE: The purpose of the present study was to investigate the effect of the unloader brace on medial compartment dynamic joint space (DJS) during gait, while simultaneously recording ground reaction force (GRF) in varus knee osteoarthritis (OA) patients using a highly accurate biplane radiography system which allowed continuous measurement of DJS from heel strike through the midstance phase of gait. The hypothesis was that DJS in the medial compartment would be greater with the unloader brace than without the brace during gait. METHODS: After 2 weeks of daily use of the unloader brace, ten varus knee OA patients (age 52 ± 8 years) walked with and without the brace on an instrumented treadmill, while biplane radiographs of the OA knees were acquired at 100 Hz. Medial compartment DJS was determined from heel strike to terminal stance (0-40% of the gait cycle) using a validated volumetric model-based tracking process that matches subject-specific 3D bone models to the biplane radiographs. The GRF during gait was collected at 1000 Hz. Repeated-measures ANOVA was used to explore differences in medial compartment DJS and GRF between the unbraced and braced conditions. A patient-reported subjective questionnaire related to the brace use was collected at the time of the test. RESULTS: Medial compartment DJS was significantly greater with the unloader brace than without the brace during gait (P = 0.005). The average difference was 0.3 mm (95% confidence interval 0.1-0.4 mm). No significant difference was observed in terms of vertical GRF between the two conditions. The questionnaire showed participants felt reduced pain when wearing the brace. CONCLUSION: The unloader brace has the significant effect of increasing medial compartment DJS during gait, which supports the underlying premise that the unloader brace reduces pain by increasing medial joint space during dynamic loading activities. LEVEL OF EVIDENCE: III.

Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.

Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process.

Inactivation of Akt by arsenic trioxide induces cell death via mitochondrial-mediated apoptotic signaling in SGC-7901 human gastric cancer cells.

Arsenic trioxide (As2O3) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As2O3. The MTT assay showed that As2O3 suppressed the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Characteristic apoptotic changes were observed in the As2O3­treated cells by Hoechst 33342 staining, and FACS analysis showed that As2O3 caused dose-dependent apoptotic cell death. As2O3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As2O3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3ß (Ser9), suggesting that As2O3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As2O3. These results demonstrated that inhibition of PI3K/Akt signaling was involved in As2O3-induced apoptosis of gastric cancer SGC-7901 cells.

Arsenic trioxide induces G2/M arrest in hepatocellular carcinoma cells by increasing the tumor suppressor PTEN expression.

Arsenic trioxide (As(2)O(3)), an effective agent against acute promyelocytic leukemia, has been reported to inhibit the viability of solid tumors cell lines recently. The detailed molecular mechanism underlying the As(2)O(3)-induced inactivation of the cdc2 and possible functional role of PTEN in the observed G2/M arrest has yet to be elucidated. Here, we assessed the role of PTEN in regulation of As(2)O(3)-mediated G2/M cell cycle arrest in Hepatocellular carcinoma cell lines (HepG2 and SMMC7721). After 24 h following treatment, As(2)O(3) induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by As(2)O(3) is associated with decreased cdc2 protein and increased phospho-cdc2(Tyr15). As(2)O(3) treatment increased Wee1 levels and decreased phospho-Wee1(642). Moreover, As(2)O(3) substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in As(2)O(3) -treated cells increased phospho-Wee1(Ser642) while decreased phospho-cdc2(Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by As(2)O(3) involved upregulation of PTEN.