Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells.

Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1. The underlying mechanisms are revealed by analysis of the signaling molecules using western blotting. In control cells, FLICE inhibitory protein in short form (FLIPS) is expressed in relatively high levels and binds to caspase 8 in ripoptosome, which supposedly sustains cell survival. However, in Tan IIA-treated cells, FLIPS is down-regulated and may thus cause homodimer formation of cleaved caspase 8, cleavage of receptor-interacting serine/threonine-protein kinases 1, 3 (RIP1, RIP3), and mixed-lineage kinase domain-like (MLKL), in turn leads to cell apoptosis. In parallel, Tan IIA causes necroptosis by forming a suggested necrosomal complex composed of RIP1/RIP3. Regarding the inhibitors, z-VAD-fmk diminishes the cleaved caspase 8, RIP1, RIP3, and MLKL induced by Tan IIA, and reconstructs the ripoptosome complex, which marks cells moving from apoptosis to necroptosis. Nec-1 recovers the Tan IIA down-regulated FLIPS, consequently causes FLIPS to form heterodimer with caspase 8 and thus block apoptosis. Meanwhile, cleaved forms of RIP1 and RIP3 were observed preventing necroptosis. Intriguingly, the cytotoxicity of tumor necrosis factor-related apoptosis-inducing ligand to HepG2 cells is enhanced by Tan IIA in a pilot study, which may be attributed to low FLIPS levels induced by Tan IIA. In short, Tan IIA simultaneously induces both Nec-1 inhibition and FLIPS regulation-mediated apoptosis/necroptosis, which has not been previously documented. Moreover, the involvement of the cleavage type of MLKL in executing necroptosis warrants further investigation.

Acidic FGF promotes neurite outgrowth of cortical neurons and improves neuroprotective effect in a cerebral ischemic rat model.

Acidic fibroblast growth factor (aFGF) is a neurotrophic factor which is a powerful neuroprotective and neuroregenerative factor of the nervous system. Prior study had shown that levels of FGFs significantly increase following ischemic injury, reflecting a physiological protection mechanism. However, few reports demonstrated the efficacy of applying aFGF in cerebral ischemia. A recent report showed that the intranasal aFGF treatment improved neurological functional recovery; however, it did not significantly reduce the lesion size in ischemic rats. The present study examines the neuroprotective effect of aFGF on cortical neuron-glial cultures under oxygen glucose deprivation (OGD)-induced cell damage and investigates whether epidural application of slow-released aFGF could improve benefit on ischemic stroke injury in conscious rats. We used a topical application of aFGF mixed in fibrin glue, a slow-release carrier, over the peri-ischemic cortex and examined such treatment on cerebral infarction and behavioral impairments of rats subjected to focal cerebral ischemia (FCI). Results demonstrate that aFGF effectively protected cortical neuron-glial cultures from OGD-induced neuronal damage. Neurite extension from cortical neurons was significantly enhanced by aFGF, mediated through activation of AKT and ERK. In addition, topical application of fibrin glue-mixed aFGF dose-dependently reduced ischemia-induced brain infarction and improved functional restoration in ischemic stroke rats. Slow-released aFGF not only protected hippocampal and cortical cell loss but reduced microglial infiltration in FCI rats. Our results suggest that aFGF mixed in fibrin glue could prolong the protective/regenerative efficacy of aFGF to the damaged brain tissue and thus improve the functional restorative effect of aFGF.

Correlated electric fluctuations in GaN nanowire devices.

We report an experimental study on the correlation spectrums between different sections of a multi-contact GaN nanowire device. Our results indicate that there exists a negative correlation between the voltage fluctuations of adjacent sections of the nanowire separated by a metal contact in the transition region between the low-frequency 1/f noise and the high-frequency white thermal noise. We suggest that this correlation is caused by the voltage fluctuation under the contact area.

Mobility asymmetry in InGaAs/InAlAs heterostructures with InAs quantum wires.

Strong asymmetry of electron mobility in InGaAs/InAlAs heterostructures (lattice matched to InP) with the presence of InAs quantum wires was observed. Self-assembled InAs quantum wires, embedded in an InGaAs matrix close to the hetero-interface, has a strong effect in electron conduction in the interface channel. The low temperature mobility for electrons moving parallel to the quantum wires is much higher than that of electrons moving perpendicular to the wires. The asymmetry in mobility is attributed to the difference in scattering cross section of the quantum wires in these two directions.

Linking watershed and eutrophication modelling for the Shihmen Reservoir, Taiwan.

The Shihmen Reservoir, located in northern Taiwan, features the second storage volume of impoundments on the island. The watershed of the Shihmen Reservoir has been subjected to serious pollutants due to anthropogenic interference. This study applies a watershed model, BASINS, to simulate the flow and nutrients loads from the watershed. BASINS then drives the CE-QUAL-W2 model for water quality predictions in the reservoir. The watershed modelling results are compared with field data. They reveal that significant nutrient loads were generated from the watershed during storms. The model calibration and verification were achieved with water surface elevation, temperature, and water quality constituents including nutrients, dissolved oxygen, and chlorophyll a in the reservoir using the eutrophication model.

Cryopreservation and biophysical properties of articular cartilage chondrocytes.

In order to successfully cryopreserve articular cartilage chondrocytes, it is important to characterize their osmotic response during the cryopreservation process, as the ice forms and the solutes concentrate. In this study, experimental work was undertaken to determine the osmotic parameters of articular cartilage chondrocytes. The osmotically inactive volume of articular cartilage chondrocytes was determined to be 44% of the isotonic volume. The membrane hydraulic conductivity parameters for water were determined by fitting a theoretical water transport model to the experimentally obtained volumetric shrinkage data; the membrane hydraulic conductivity parameter L(Pg) was found to be 0.0633 microm/min/atm, and the activation energy E, 8.23 kcal/mol. The simulated cooling process, using the osmotic parameters obtained in this study, suggests a cooling rate of 80 degrees C/min for the cryopreservation of the articular cartilage chondrocytes of hogs. The data obtained in this study could serve as a starting point for those interested in cryopreservation of chondrocytes from articular cartilage in other species in which there is clinical interest and there are no parameters for prediction of responses.

Physical heights of children with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings.

PURPOSE: To evaluate low dose-rate radiation effects on the physical heights of children staying in apartments with 60Co-contaminated steel construction. MATERIALS AND METHODS: Children who once resided in radiocontaminated apartments since early 1983 were examined for height and body weight status from age 1 month to 18 years and before they moved out of the apartments. The physical heights and body weights of 21 898 age- and sex-matched non-exposed children from a nationwide school surveillance in 1997-98 were taken as controls. The physical height data were shown as height percentiles (HP) compared with reference children and age-specific relative height differences (RHD). RESULTS: HP and RHD in 48 exposed boys and 37 girls were analysed using generalized estimating equations (GEE), which accounted for multiple measurements and correlation between these measurements in the same individuals during this period. After adjusting for effects from parental heights and body mass index (BMI), clear dose-related decreases in HP and RHD were observed in the exposed boys with a cumulative exposure > 60 mSv. CONCLUSIONS: Prolonged low dose-rate y-radiation exposure was associated with adverse effects on the physical heights of growing boys, but were less apparent in the exposed girls.

The fuzzy crystallization algorithm: a new approach to complex systems modeling.

A new identification method for fuzzy modeling is introduced. Since the method has some analogy with the process of material crystallization in nature, the name of fuzzy crystallization algorithm (FCA) is given to this novel approach. This method accomplishes structure identification and parameter identification at the same time, and possesses the properties of simplicity, flexibility, and high calculation speed. Compared with other modeling strategies, it is easier to construct a model with a specific accuracy. Numerical examples are provided to demonstrate the performance of this approach.

Comparison of the one-and-a-half-year results of closure of patent ductus arteriosus by transcatheter coils placement with surgical ligation.

Patent ductus arteriosus (PDA) is a common type of congenital cardiovascular lesion. It usually needs surgical ligation in a full-term baby after 1 year of age. Transcatheter implantation of coils was introduced for the closure of small- to moderate-sized PDA in 1992. From November 1995 to November 1998, the authors closed the PDA in 153 patients by transcatheter implantation of coils and by surgical ligation in 10 patients. One hundred fourteen of them were studied for more than 1(1/2) years. The regular follow-up studies, including physical examination; electrocardiography; and pulsed, continuous-wave, and color Doppler flow mapping, were performed on day one and day 2, and 1 week, 1 month, 3 months, 6 months, and 1 year after the procedure. The results of the closure of PDA by surgical ligation or coil placement were compared and analyzed in all the patients.

Treatment of pulmonary atresia with intact ventricular septum in early infancy.

BACKGROUND: Early treatment for the neonate with pulmonary atresia and intact ventricular septum (PA-IVS) is important if a high mortality rate is to be avoided. The treatment includes prostaglandin administration, balloon atrial septostomy, pulmonary valvotomy, a shunting procedure and patch repair for the right ventricular outflow tract (RVOT). This study discusses the early treatment and risk factors of this disease that are essential for assessing the risk of surgery and predicting outcome. METHODS: The medical records, echocardiograms, catheterization data and cineangiograms of 29 patients with PA-IVS diagnosed at our institution from 1987 to 1997 were reviewed retrospectively. Clinical manifestations including age, body weight, sex ratio, type of surgery and outcome were analyzed. RESULTS: Three of four patients with a right ventricular volume of less than 1 ml died, and all patients with a right ventricular volume of greater than 2 ml survived. Four of six patients with a tricuspid valvular area of between 0.25 and 0.5 cm2 died, but patients with an area of greater than 0.5 cm2 survived. One case with a monopartite right ventricle died. Patients with a bipartite or tripartite right ventricle had higher survival rates than those with a monopartite right ventricle. Patients with a the right ventricle dependent coronary sinusoid had a higher risk for mortality, even after surgery, than those with normal coronary circulation. CONCLUSIONS: A small right ventricular volume, the presence of a coronary sinusoid involving the right ventricle, a short linear length of the tricuspid valve and a small area of the tricuspid valve were the risk factors associated with a negative outcome in neonates with PA-IVS.

Effects of waglerin-I on neuromuscular transmission of mouse nerve-muscle preparations.

The effects of waglerin-I, a toxin from Trimeresurus wagleri, on neuromuscular (NM) transmission were studied on the phrenic nerve-diaphragm preparation and triangularis sterni nerve-muscle preparation of mice. The toxin (1.2-4.0 microM) reversibly inhibited the indirectly elicited twitch tension of the diaphragm and decreased the ACh-elicited muscle contracture of chronically denervated diaphragm, while the directly elicited twitch tension was not affected. The toxin reversibly decreased the amplitude of miniature endplate potential (MEPP) at 0.52 microM and endplate potential (EPP) at 1.2-4 nM. The toxin (120 nM-0.4 microM) also decreased the quantal content of EPP. The perineural waveforms were recorded with an extracellular electrode placed into the perineural sheaths of motor nerves of M. triangularis sterni. The toxin (4 microM) did not alter the amplitudes of waveforms related to sodium and potassium currents of the nerve terminal action potential, while the waveform related to calcium current was decreased. It is concluded that the toxin acts on both presynaptic and postsynaptic sites of the mouse motor endplate, and that the presynaptic effect is apparently more potent than the postsynaptic effect.

The combined prostatectomy.

A modified method of suprapubic-retropubic prostatectomy is described. This technique appears to offer several advantages over other open methods of prostatectomy. Dissection anterior and lateral to the surgical capsule is minimal. Simultaneous access to the lumen of the expanded prostatic urethra, vesical neck and bladder permits inspection of all areas and establishes nearly complete hemostasis. Corrective procedures at the vesical neck are accomplished easily, additional suprapubic transvesical drainage is unnecessary and closure of the prostatic urethra is simplified. Three-fourths of our patients were discharged from the hospital 8 days postoperatively. The amount of blood loss, mortality and morbidity were extremely low.

Cell-free protein synthesis by kidney from the aging female Fischer F344 rat.

This is the first report to describe and characterize a cell-free protein synthesis system derived from kidney tissue. The optimum conditions for [3H]-valine incorporation into protein by the post-mitochondrial supernatant from whole kidneys were found to be: pH 6.9, 7.5 mM MgCl2, 150 mM KCl, 10 mM ATP, and 2 mM GTP. The cell-free protein-synthetising activities of kidneys isolated from 4.5-, 7.5-, 22-, and 31-month-old female Fischer F344 rats were measured using the post-mitochondrial supernatant. A 73-87% decrease in cell-free protein synthesis was observed between 4.5 and 31 months of age. Both the cell sap and microsomal fractions of the kidney post-mitochondrial supernatant from old rats were less active in protein synthesis than these fractions from the kidneys of young rats. No age-related change in the activity of RNAase in the kidney post-mitochondrial supernatant was observed. Kidney ribosomes stripped of endogenous mRNA were found to be active in poly(uridylic acid)-directed polyphenylalanine synthesis. The effect of aging on the fidelity of translation was determined by measuring poly(uridylic acid)-directed [14C]-phenylalanine and [3H]leucine incorporation by kidney ribosomes isolated from rats of various ages. No age-related change in the fidelity of poly(uridylic acid) translation by kidney ribosomes was observed.