Biomechanical study of temporomandibular joints of patients with temporomandibular disorders under incisal clenching: A finite element analysis.

Temporomandibular disorders (TMD) encompass a collection of pathologies. Within the multitude of etiological factors contributing to TMD, mechanical factors hold significant importance. The aim of this investigation was to assess the magnitude and distribution of stresses encountered by the temporomandibular joints (TMJs) during incisal clenching among TMD patients while also elucidating the mechanical pathogenesis underlying TMD. Ten asymptomatic subjects and ten TMD patients were recruited. The Control, Bilateral, and Unilateral groups were set. The contact stress, maximum principal stress, and minimum principal stresses of TMJ structures among the groups were compared. In addition, comparisons of the contact stress distribution among the groups were adopted. In the Control and Bilateral groups, the magnitudes of stresses (contact stress, maximum and minimum principal stresses) between the right and left sides showed no significant difference (P > 0.05). For unilateral TMD patients,the minimum principal stress on the condyle in the Uni-N group (the normal side) was significantly greater than thatin the Uni-T group (the TMD side)(P = 0.016, mean difference 9.99 MPa [95 %CI: 3.11 to 16.87]). Furthermore, stresses on the condyle and fossa of the patients were significantly greater than those of asymptomatic subjects (P < 0.05). The contact stress distributions were concentrated in the Control group while irregular in the TMD groups. In conclusion, asymmetrical contact stress distributions were observed in unilateral TMD, with excessive stresses on the healthy side. The protection of the healthy TMJ during treatment is recommended for patients with unilateral TMD.

Demethylzeylasteral (T-96) Alleviates Allergic Asthma via Inhibiting MAPK/ERK and NF-κB Pathway.

INTRODUCTION: Demethylzeylasteral (T-96), a new extract of Tripterygium wilfordii Hook F, exerted immunomodulatory properties in autoimmune diseases, but its effect on airway inflammatory diseases remains unclear. Our study aims to explore the protective effect and underlying mechanism of T-96 in allergic asthma. METHODS: The OVA-induced asthmatic mice were administered by gavage with T-96 (0.1 mg/10 g, 0.3 mg/10 g, or 0.6 mg/10 g) 1 h before each challenge. The airway hyperresponsiveness was assessed, pathological changes were evaluated by HE and PAS staining, and expressions of Th2 cytokines were determined by PCR and ELISA. The activation of MAPK/ERK and NF-κB pathway was assessed by western blot. RESULTS: T-96 significantly relieved airway hyperresponsiveness in asthmatic mice, evidenced by reduced airway resistance (Raw) and increased lung compliance dynamic compliance (Cdyn). Also, enhanced inflammatory infiltration and mucus hypersecretion were ameliorated in lungs of asthmatic mice following increasing doses of T-96 treatment, accompanied by decreased eosinophils in bronchoalveolar lavage fluid (BALF), IgE and OVA-specific IgE levels in serum, and downregulated IL-5 and IL-13 expressions in BALF and lung tissues as well. Notably, phosphorylation levels of p38 MAPK, ERK, and p65 NF-κB were obviously increased in asthmatic mice compared with the control group, which were then abrogated upon T-96 treatment. CONCLUSION: This study first revealed that T-96 alleviated allergic airway inflammation and airway hyperresponsiveness via inhibiting MAPK/ERK and NF-κB pathway. Thus, T-96 could potentially act as a new anti-inflammatory agent in allergic asthma.

A ground reaction force model of speed skating based on non-contact measurement system.

Accurate collection and analysis of ground reaction force (GRF) data are crucial for optimizing the technical movements of speed skaters; however, it has been a challenge for the limitations of experimental equipment and application scenarios. Therefore, we proposed a novel approach for estimating GRF based on kinematics obtained from markerless video tracking systems and achieved low errors compared with the experimental data. Our method allows for further biomechanical analysis, including muscle force and power, during speed skating competitions.

Molecular simulation of Rayleigh-Brillouin scattering in binary gas mixtures and extraction of the rotational relaxation numbers.

Rayleigh-Brillouin scattering (RBS) in gases has received considerable attention due to its applications in LIDAR (light detection and ranging) remote sensing and gas property measurements. In most cases, the RBS spectra in the kinetic regime are calculated based on kinetic model equations, which are difficult to be applied to complex gas mixtures. In this work, we employ two widely used molecular simulation methods, i.e., direct simulation Monte Carlo (DSMC) and molecular dynamics (MD), to calculate the spontaneous RBS spectra of binary gas mixtures. We validate these two methods by comparing the simulation results for mixtures of argon and helium with the experimental results. Then we extend the RBS calculations to gas mixtures involving polyatomic gases. The rotational relaxation numbers specific to each species pair in DSMC are determined by fitting the DSMC spectra to the MD spectra. Our results show that all the rotational relaxation numbers for air composed of N_{2} and O_{2} increase with temperature in the range of 300-750 K. We further calculate the RBS spectra for binary mixtures composed of N_{2} and one noble monatomic gas, and the simulation results show that the rotational relaxation of N_{2} is greatly affected by the mass of the noble gas atoms. This work demonstrates that RBS is a promising and alternative way to study the rotational relaxation process in gas mixtures.

Complexity Evaluation of an Environmental Control and Life-Support System Based on Directed and Undirected Structural Entropy Methods.

During manned space missions, an environmental control and life-support system (ECLSS) is employed to meet the life-supporting requirements of astronauts. The ECLSS is a type of hierarchical system, with subsystem-component-single machines, forming a complex structure. Therefore, system-level conceptual designing and performance evaluation of the ECLSS must be conducted. This study reports the top-level scheme of ECLSS, including the subsystems of atmosphere revitalization, water management, and waste management. We propose two schemes based on the design criteria of improving closure and reducing power consumption. In this study, we use the structural entropy method (SEM) to calculate the system order degree to quantitatively evaluate the ECLSS complexity at the top level. The complexity of the system evaluated by directed SEM and undirected SEM presents different rules. The results show that the change in the system structure caused by the replacement of some single technologies will not have great impact on the overall system complexity. The top-level scheme design and complexity evaluation presented in this study may provide technical support for the development of ECLSS in future manned spaceflights.

The short-term safety and effectiveness of a new distal perforating stent graft in Type B aortic dissection: a retrospective study.

BACKGROUND: Spinal artery ischemia (SCI) events can result from over coverage of the descending thoracic aorta with a coated stent during Thoracic Endovascular Aortic Repair (TEVAR). The aim of this study was to determine whether a new distal perforating stent could reduce the incidence of spinal cord ischemia while remodeling the true lumen. METHODS: TBAD patients treated with Talos stent in the vascular surgery Department of Yan 'an Hospital affiliated to Kunming Medical University between December 2017 and October 2019 were retrospectively analyzed to investigate the short-term safety and effectiveness of Talos stent. RESULTS: A total of the 20 patients, including 14 males and 6 females, with an average age of 52.65 ± 8.98 years (range 37-68 years), were included in the analysis. Stent-grafts were successfully implanted in all patients under local anesthesia, with a technical success rate of 100%. The average operation time was 50.75 ± 13.01 min. A total of 2 cases (10%) presented chest pain associated with intercostal artery ischemia that was relieved on the 3rd and 5th postoperative day, respectively. Postoperative mean follow-up was 16.15 ± 3.99 months. No paraplegia or other complications occurred. And stenting did not induce new tears. No migration, deformation, or fracture of the stents occurred. There was a significant difference in the remolding of the true lumen preoperatively and at 12 months postoperatively (P < 0.05). CONCLUSIONS: Talos stent has achieved satisfactory clinical treatment results in short term.

Influences of Different Architectures on the Thermodynamic Performance and Network Structure of Aircraft Environmental Control System.

The environmental control system (ECS) is one of the most important systems in the aircraft used to regulate the pressure, temperature and humidity of the air in the cabin. This study investigates the influences of different architectures on the thermal performance and network structure of ECS. The refrigeration and pressurization performances of ECS with four different architectures are analyzed and compared by the endoreversible thermodynamic analysis method, and their external and internal responses have also been discussed. The results show that the connection modes of the heat exchanger have minor effects on the performance of ECSs, but the influence of the air cycle machine is obvious. This study attempts to abstract the ECS as a network structure based on the graph theory, and use entropy in information theory for quantitative evaluation. The results provide a theoretical basis for the design of ECS and facilitate engineers to make reliable decisions.

Endovascular aortic repairs combined with looping-chimney technique for repairing aortic arch lesions and reconstructing left common carotid artery.

BACKGROUND: The aim of this retrospective study was to evaluate the feasibility and efficacy of thoracic endovascular aortic repairs (TEVAR) combined with looping chimney technique (LCT) for repairing aortic arch lesions and reconstructing left common carotid artery. METHODS: Total of 14 patients (mean age 52.86±14.46 years; range, 27-79; 10 men, 4 women) were included in the study from December 2016 to December 2018. Aortic arch pathologies of all patients with insufficient proximal landing zone (PLZ) were repaired by TEVAR under local anesthesia, before TEVAR, the left common carotid artery (LCCA) was protected by the guiding sheath from the retrograde brachial access, after aortic stent graft deployed, chimney graft was implanted to restore LCCA by LCT if necessary. All patients underwent computed tomography angiograph (CTA) 2 weeks, 3 months, 6 months and 1 year after surgery. RESULTS: Pathology results of 14 patients included: type B aortic dissection (n=8), penetrating aortic ulcers (n=1), retrograde type A aortic dissection (n=1), thoracic aortic aneurysm (TAA) (n=2), and thoracic aortic pseudoaneurysm (n=2). In all patients, aortic arch lesions were repaired by TEVAR; while LCCA were successfully reconstructed by the LCT. In one case, the innominate artery (IA) was simultaneously reconstructed through the same percutaneous right brachial artery (RBA) access. Coiling eliminated type Ia endoleak in 3 patients, and type II endoleak vanished by plugging left subclavian artery (LSA) in 2 patients. In four patients, the chimney stent (CG) of LCCA was partially compressed and then another bare stent was implanted to restore patency rate. The mean follow-up duration was 9.77±6.64 months (range, 0-24) and no combinations were observed in 13 patients; except in one patient who died of cerebral hemorrhage due to abnormal coagulation function. CONCLUSIONS: TEVAR combined with LCT has shown to be suitable surgical approach for aortic arch lesions. Either covered intentionally or inadvertently, the LCCA could be safely and effectively reconstructed via percutaneous RBA access. Short-term follow-up demonstrated satisfactory morbidity and mortality in high-risk patients; however, longer follow-up is required to assess the effectiveness and durability of this innovative endovascular procedure.

Effects of vibration intensity on lower limb joint moments during standing.

Muscle activity and joint moment of the lower limbs can provide different information about the stimulation of controlled whole-body vibration (CWBV) on human body. Previous studies investigated the immediate effects of the intensity of CWBV on enhancing lower-limb muscle activity. However, no study has examined the possible influence of CWBV intensity on joint loading. It remains unexplored how CWBV intensity impacts joint loading. This study was carried out (1) to quantify the effects of CWBV intensity in terms of vibration frequency and amplitude on the lower limb joint moments and (2) to examine the relationship between leg joint moments and vibration intensity characterized by the platform's acceleration, that is determined by frequency and amplitude, during standing among young adults. Thirty healthy young adults participated in this study. Each participant experienced nine vibration intensity levels dependent upon the frequency (10, 20, and 30 Hz) and amplitude (1, 2, and 3 mm) while standing on a side-alternating vibration platform. Their body kinematics and vertical reaction forces between the feet and platform were collected. Inverse dynamics was employed to calculate the resultant moment for the ankle, knee, and hip joints in the sagittal plane. Our results revealed that the root-mean-square moment significantly increases with increasing vibration frequency or amplitude for all three joints. Further, all joint moments are strongly and positively correlated with the platform acceleration.

Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA.

Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for celastrol is still unclear. As celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both celastrol and PA could bind MD2, and that celastrol could expel PA from cells. Finally, celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2.

Demethylzeylasteral (ZST93) inhibits cell growth and enhances cell chemosensitivity to gemcitabine in human pancreatic cancer cells via apoptotic and autophagic pathways.

The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. Demethylzeylasteral (ZST93) is a novel triterpenoid monomer extracted from the xylem of Tripterygium roots. Our study aimed to assess the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells. The effects of ZST93 on cancer cell proliferation, cell cycle distribution, apoptosis and autophagy were evaluated in various human pancreatic cancer cell lines, and the antitumor effects of ZST93 alone and in combination with gemcitabine were identified in a xenograft mouse model. The results showed that ZST93 could inhibit the proliferation of pancreatic cancer cells and arrest cell cycle at G0/G1 phase by regulating the expression of Cyclin D1 and Cyclin A2. Moreover, ZST93 killed pancreatic cancer cells through two different mechanisms: inducing autophagic cell death at low concentrations and apoptotic cell death at high concentrations. Furthermore, ZST93 could enhance the chemosensitivity of pancreatic cancer cells to gemcitabine both in vitro and in vivo through modulation of the cross talk between autophagy and apoptosis. ZST93 is a potential therapeutic agent for developing novel therapeutic strategies in human pancreatic cancer.

Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by celastrol.

BACKGROUND: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention. METHODS AND RESULTS: Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in celastrol-treated cells. NF-κB inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not. CONCLUSIONS: For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti-cancer effects.

Demethylzeylasteral (T-96) Treatment Ameliorates Mice Lupus Nephritis Accompanied by Inhibiting Activation of NF-κB Pathway.

BACKGROUND: Inflammation plays a vital role in the pathogenesis in lupus nephritis (LN), which is largely attributable to the activation of nuclear factor kappa B (NF-κB) signal pathway. NF-κB up-regulates pro-inflammatory mediators, such as TNF-α, cyclo-oxygenase-2 (COX-2) and ICAM-1, and promotes macrophage infiltration into renal tissue, further inducing the progression of LN. Over the past 30 years, research has demonstrated that Tripterygium wilfordii Hook F (TWHF) possesses potent anti-inflammatory and immunosuppressive activities, and that demethylzeylasteral (T-96), an extract of TWHF, may be one of the responsible compounds. Here, we investigate the pharmacodynamic role and therapeutic mechanism by which T-96 suppresses inflammation and reduces renal pathology in the lupus-prone MRL/lpr mice. METHODS: Forty-eight MRL/lpr mice were equally randomly divided into 6 groups (1.2, 0.6 or 0.3 mg/10 g T-96, 0.022 pills/10 g kang lang chuang san (one of Traditional Chinese herb as positive control), 0.125 mg/10 g prednisone and 0.1 ml/10 g normal saline as the LN disease control group). Also, eight WT C57BL/6 mice were used as normal control. After treatment by gavage with 0.10 ml/10 g/day volumes for 8 weeks, all mice were sacrificed and renal tissues were collected. The amount of 24 h proteinuria and the levels of anti-dsDNA antibody in serum were assessed respectively at weeks 0, 4 and 8. Inflammation, cytokines and NF-κB levels were assessed by histological examinations, immunohistochemical analyses and Western blot analyses. RESULTS: In comparison with untreated MRL/lpr mice, mice treated with 1.2 and 0.6 mg/10 g of T-96 showed a significant improvement in 24 h proteinuria and the levels of anti-dsDNA antibody in serum. In addition, T-96 reduced the secretion of pro-inflammatory mediators such as TNF-α, COX-2 and ICAM-1, and the infiltration of macrophages in renal tissue. Moreover, T-96 significantly suppressed phosphorylations of cytoplasmic IKK and nuclear p65. CONCLUSION: This study suggests that T-96 exhibits reno-protective effects in LN accompanied by inhibiting the activation of NF-κB, reducing the downstream pro-inflammatory mediators and thus restricting macrophage infiltration. Because of these potent properties, T-96 should be considered as a promising therapeutic drug for LN.

Peptide deformylase inhibitor actinonin reduces celastrol's HSP70 induction while synergizing proliferation inhibition in tumor cells.

BACKGROUND: Celastrol is a promising anti-tumor agent, yet it also elevates heat shock proteins (HSPs), especially HSP70, this effect believed to reduce its anti-tumor effects. Concurrent use of siRNA to increase celastrol's anti-tumor effects through HSP70 interference has been reported, but because siRNA technology is difficult to clinically apply, an alternative way to curb unwanted HSP70 elevation caused by celastrol treatment is worth exploring. METHODS: In this work, we explore three alternative strategies to control HSP70 elevation: (1) Searching for cancer cell types that show no HSP70 elevation in the presence of celastrol (thus recommending themselves as suitable targets); (2) Modifying HSP70-inducing chemical groups, i.e.: the carboxyl group in celastrol; and (3) Using signaling molecule inhibitors to specifically block HSP70 elevation while protecting and/or enhancing anti-tumor effects. RESULTS: The first strategy was unsuccessful since celastrol treatment increased HSP70 in all 7 of the cancer cell types tested, this result related to HSF1 activation. The ubiquity of HSF1 expression in different cancer cells might explain why celastrol has no cell-type limitation for HSP70 induction. The second strategy revealed that modification of celastrol's carboxyl group abolished its ability to elevate HSP70, but also abolished celastrol's tumor inhibition effects. In the third strategy, 11 inhibitors for 10 signaling proteins reportedly related to celastrol action were tested, and five of these could reduce celastrol-caused HSP70 elevation. Among these, the peptide deformylase (PDF) inhibitor, actinonin, could synergize celastrol's proliferation inhibition. CONCLUSIONS: Concurrent use of the chemical agent actinonin could reduce celastrol's HSP70 elevation and also enhance proliferation inhibition by celastrol. This combination presents a novel alternative to siRNA technology and is worth further investigation for its potentially effective anti-tumor action.

[Application of quality by design concept for the optimization of an analytical method for rhubarb anthraquinones in rat plasma].

A robust high performance liquid chromatography with fluorescence detection method (HPLC-FLD) was developed for the determination of five rhubarb anthraquinones in rat plasma using a quality by design approach. A Plackett-Burman design was utilized to screen the effects of methanol content, the pH value of mobile phase, the flow rate, column temperature, and injection volume on peak resolution, number of the theoretical plate, retention time of the last eluted peak, and tailing factor. The results showed that the methanol content in mobile phase, flow rate, and column temperature were statistically significant (p < 0.05). A Box-Behnken experimental design with response surface methodology (RSM) was then utilized to evaluate the effects of these three factors on the selected responses. Derringer' s desirability function was used for the evaluation of the chromatographic goals. The optimum conditions for separation were as follows: an isocratic mobile phase consisting of methanol/0.1% H3PO4 (81.4/18. 6, v/v), a flow rate of 1.1 mL/min, and a column temperature of 31 degrees C. The excitation and emission wavelengths were 440 nm and 540 nm, respectively. The proposed method showed good prediction ability. The results clearly showed that quality by design concept could be effectively applied to optimize the HPLC method.

[Effects of triptolide-medicated serum on secretion function of adrenocortical cells isolated from rats].

OBJECTIVE: To study the effects of triptolide-medicated serum on secretory function of adrenocortical cells isolated from rats. METHODS: Thirty SD rats were randomly divided into control group, prednisone group, and low-, medium- and high-dose triptolide groups. Rats were administered with normal saline, prednisone and low-, medium- and high-dose triptolide respectively by gastrogavage to prepare sera containing drugs. Primary adrenocortical cells were isolated from normal male rats and cultured with sera containing drug for 48 hours. Expression of proliferating cell nuclear antigen (PCNA) was observed by immunohistochemical method and number of PCNA-positive cells was counted. Ultrastructure of adrenocortical cells was observed under a transmission electron microscope. Content of corticosterone in supernatant of adrenocortical cell culture was detected by enzyme-linked immunosorbent assay, and real-time fluorescence quantitative polymerase chain reaction (PCR) was employed to investigate the expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA. RESULTS: As compared with the control group, content of corticosterone in supernatant of adrenocortical cell culture and expression of 3beta-HSD mRNA were significantly increased in the triptolide-treated groups, and the numbers of PCNA-positive cells were increased in the medium- and high-dose triptolide groups, however, they were decreased in the prednisone group. CONCLUSION: Triptolide-medicated serum can increase the secretion of corticosterone in rat adrenocortical cells in vitro.

Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way.

Celastrol, a novel HSP90 inhibitor, has recently attracted much attention due to its potential in multiple applications, such as anti-inflammation use, degenerative neuron disease relief, and tumor management. At present, the studies in celastrol's effects on HSP90's clients have focused on the kinase sub-population, while another key sub-population, nuclear transcription factors (TFs), is not being well-explored. In this study, we observe the effects of celastrol on 18 TFs (belonging to HSP90 clients) in three human cell lines: MCF-7 (breast cancer), HepG2 (hepatoma), and THP-1 (monocytic leukemia). The results show that at least half of the detectable TFs were affected by celastrol, though the effect patterns varied with cell type and dosage. Bi-directional regulations of some TFs were identified, a phenomenon not yet seen with other HSP90 inhibitors. Celastrol's capability to affect multiple TFs was consistent with its altering HSP90/TFs interactions and disrupting HSP90/Hop interaction, in addition to the reported damaging HSP90/Cdc37 interaction. This work confirms, for the first time, that celastrol has broad effects on TFs belonging to HSP90's clients, casts new light on understanding these reported actions, and suggests new possible applications for celastrol, such as diabetes management.

HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way.

BACKGROUND: Because some of heat shock protein 90's (HSP90) clients are key cell cycle regulators, HSP90 inhibition can affect the cell cycle. Recently, celastrol is identified both as a novel inhibitor of HSP90 and as a potential anti-tumor agent. However, this agent's effects on the cell cycle are rarely investigated. In this study, we observed the effects of celastrol on the human monocytic leukemia cell line U937 cell cycle. RESULTS: Celastrol affected the proliferation of U937 in a dose-dependent way, arresting the cell cycle at G0/G1 with 400 nM doses and triggering cell death with doses above 1000 nM. Cell cycle arrest was accompanied by inhibition of HSP90 ATPase activity and elevation in HSP70 levels (a biochemical hallmark of HSP90 inhibition), a reduction in Cyclin D1, Cdk4 and Cdk6 levels, and a disruption of the HSP90/Cdc37/Cdk4 complex. The observed effects of celastrol on the U937 cell cycle were thiol-related, firstly because the effects could be countered by pre-loading thiol-containing agents and secondly because celastrol and thiol-containing agents could react with each other to form new compounds. CONCLUSIONS: Our results disclose a novel action of celastrol-- causing cell cycle arrest at G0/G1 phase based upon thiol-related HSP90 inhibition. Our work suggests celastrol's potential in tumor and monocyte-related disease management.

Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation model.

In this study, we examined the immunosuppressive activity of demethylzeylasteral (T-96), isolated from the traditional Chinese herbal medicine, Tripterygium wilfordii Hook f. Its immunosuppressive effect was investigated using mouse splenocytes in vitro, and in an in vivo rat kidney transplant model. T-96 inhibited mouse splenocyte proliferation in a dose dependent manner. In the rat kidney transplant study, rats were randomly divided into eight groups following kidney transplantation, and different doses of T-96 or cyclosporin A (CsA) were administered to each group. T-96 alone at doses of 10 or 20 mg/kg/day significantly prolonged the survival of kidney-transplanted rats, compared with transplanted but untreated control rats. A combination of T-96 and prednisone also significantly prolonged survival: 10 mg/kg/day T-96 with 10 mg/kg/day prednisone increased the survival time to 31.8+/-6.5 days. Moreover, the combination of T-96 and prednisone was also effective in suppressing rejection of rat transplanted kidneys. These results demonstrate the strong immunosuppressive activity of T-96 and suggest a possible clinical use for T-96 as an immunosuppressive agent in the fields of organ transplantation and autoimmune disorders.

Compact 10 GHz loopback arrayed-waveguide grating for high-fidelity optical arbitrary waveform generation.

We demonstrate a high-performance optical arbitrary waveform shaper based on a single 10 GHz arrayed-waveguide grating with 64 loopback waveguides and integrated amplitude and phase modulators on each waveguide. The design is compact and self-aligning and allows for bidirectional operation. The device's complex transfer function is manipulated and measured over the full 640 GHz passband. To demonstrate optical arbitrary waveform shaping, high-fidelity 15-line shaped waveforms are measured with cross-correlation frequency-resolved optical gating.