Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer ...prevention. Thus, exploring novel and effective candidate agents with low toxicity for chemoprevention is essential and urgent. Houttuynia cordata Thunb. (Saururaceae) (H. cordata), which is a widely used herbal medicine and is also popularly consumed as a healthy vegetable, exhibits anti-inflammatory, antioxidant and antitumor activity. However, the chemopreventive effect of H. cordata against benzo(a)pyrene (BaP)-initiated lung tumorigenesis and the underlying mechanism remain unclear.
A BaP-stimulated lung adenocarcinoma animal model in A/J mice in vivo and a normal lung cell model (BEAS.2B) in vitro were established to investigate the chemopreventive effects of H. cordata and its bioactive compound 2-undecanone against lung tumorigenesis and to clarify the underlying mechanisms.
H. cordata and 2-undecanone significantly suppressed BaP-induced lung tumorigenesis without causing obvious systemic toxicity in mice in vivo. Moreover, H. cordata and 2-undecanone effectively decreased BaP-induced intracellular reactive oxygen species (ROS) overproduction and further notably protected BEAS.2B cells from BaP-induced DNA damage and inflammation by significantly inhibiting phosphorylated H2A.X overexpression and interleukin-1β secretion. In addition, H. cordata and 2-undecanone markedly activated the Nrf2 pathway to induce the expression of the antioxidative enzymes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Nrf2 silencing by transfection with Nrf2 siRNA markedly decreased the expression of HO-1 and NQO-1 to diminish the reductions in BaP-induced ROS overproduction, DNA damage and inflammation mediated by H. cordata and 2-undecanone.
H. cordata and 2-undecanone could effectively activate the Nrf2-HO-1/NQO-1 signaling pathway to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation induced by BaP stimulation and playing a role in the chemoprevention of BaP-induced lung tumorigenesis. These findings provide new insight into the pharmacological action of H. cordata and indicate that H. cordata is a novel candidate agent for the chemoprevention of lung cancer.
A mathematical model has been developed to analyze transient fluid flow and inclusions transport in a slab continuous casting mold, considering the effects of electromagnetic brake (EMBr) arrangement ...and magnetic field strength. Transient flow of molten steel in the mold is calculated by using the large eddy simulation. The electromagnetic force is incorporated into the Navier–Stokes equation. The transport of inclusion inside the mold is calculated using the Lagrangian approach based on the transient flow field. The predicted results of this model are compared with the measurements of the ultrasonic testing of the rolled steel plates and the water model experiments. The transient asymmetrical flow pattern and inclusion transport inside the mold exhibits satisfactory agreement with the corresponding measurements. With electromagnetic brake effect, the velocities around the braking region are significantly suppressed, and the recirculating flow in the lower part drops and tends to develop a plug-like flow. The EMBr arrangement has an insignificant effect on the overall removal fraction of inclusions, especially for larger inclusions. The inclusion removal rate for the flow-control mold (FCM arrangement) reduces instead compared with no EMBr, especially for smaller inclusions.
Gas injection through the submerged entry nozzle (SEN) into the continuous casting mold can be an effective approach for preventing SEN clogging and promoting the floatation of the non‐metallic ...inclusions. However, sometimes the exposed slag eyes due to gas injection appear on the top surface of the liquid slag layer, resulting in heat losses, re‐oxidation, and nitrogen pickup in the molten steel. An Eulerian multiphase‐flow model is developed to predict the argon‐steel‐slag three‐phase flow in a slab continuous casting mold. All the phases are treated based on Eulerian approach. The mathematical model is compared with the industrial observations and the water model experiments. Both of physical and numerical results reproduce the phenomenon of the high gas concentration at the SEN exit port. Most of the argon bubbles stay below the slag layer for quite long time because the slag blocks their floatation. Furthermore, the argon bubbles would gradually gather in a dense plume while escaping through the slag layer. Scattered argon exit spots are found at the top surface of slag layer. Two main locations of the exposed slag eye are found: 1) adjacent to the SEN; 2) at the mold's mid‐section at the position where a concentrated argon plume breaches through the slag layer. The near‐SEN exposed eye occurs under any of considered conditions. The one at the mid‐section is formed when the meniscus convex reaches a critical level, been dependent on the casting conditions.
The exposed slag eyes due to gas injection appear on the top surface of the mold are studied by an Eulerian multiphase‐flow model. Two main locations of exposed slag eye are found: 1) adjacent to the SEN; 2) at the mold's mid‐section at the position where a concentrated argon plume breaches through the slag layer.
Lagrangian tracking model combined with Eulerian multi-phase model is employed to predict the time-dependent argon–steel–slag–air quasi-four-phase flow inside a slab continuous casting mold. The ...Eulerian approach is used for the description of three phases (molten steel, liquid slag, and air at the top of liquid slag layer). The dispersed argon bubble injected from the SEN is treated in the Lagrangian way. The complex interfacial momentum transfers between various phases are considered. Validation is supported by the measurement data of cold model experiments and industrial practice. Close agreements were achieved for the gas volume fraction, liquid flow pattern, level fluctuation, and exposed slag eye phenomena. Many known phenomena and new predictions were successfully reproduced using this model. The vortex slag entrapment phenomenon at the slag–steel interface was obtained using this model, some small slag drops are sucked deep into the liquid pool of molten steel. Varying gas flow rates have a large effect on the steel flow pattern in the upper recirculation zone. Three typical flow patterns inside the mold with different argon gas flow rates have been obtained: double roll, three roll, and single roll. Effects of argon gas flow rate, casting speed, and slag layer thickness on the exposed slag eye and level fluctuation at the slag–steel interface were studied. A dimensionless value of
H
ave
/
h
was proposed to describe the time-averaged level fluctuation of slag–steel interface. The exposed slag eye near the SEN would be formed when the value of
H
ave
/
h
is larger than ~0.4.
Connexin 43 (Cx43), a vital gap junction protein in tumor microenvironment (TME), is a novel molecular target for melanoma chemotherapeutics due to its tumor suppressive function. Dioscin, an herbal ...steroidal saponin, exerts anti‐tumor effects while the underlying mechanism is unclear. Using WB, FACS, and immunofluorescence methodologies, we found dioscin significantly activated the transcription and translation of Cx43 via the retinoid acid signaling pathway and simultaneously enhanced the transporting function of Cx43. Through stimulating Cx43, dioscin remarkably suppressed the migratory and invasive capacities of B16 cells, and notably decreased pluripotency markers of cancer stem cells and epithelial‐to‐mesenchymal transition in B16 cells and animal tumor tissues. Conversely, dioscin improved the secretion of pro‐inflammatory cytokines (IL‐6, TNFα, and IL‐1β), and the phagocytic capacity of tumor‐associated macrophages by increasing M2‐to‐M1 phenotype transition. More strikingly, even in Cx43 functional deficient B16 and RAW264.7 cells, dioscin still dramatically reversed the aggravated tumor malignancy and reduced macrophage phagocytic activity. Two classical metastasis animal models were utilized in vivo and results showed that dioscin showed significant anti‐metastatic effects, which is closely related to the expression of Cx43 either in in situ tumor or metastatic lung nodes. In conclusion, dioscin targets Cx43 to suppress the tumor cell malignancy and activate macrophage sensitivity, thereby targeting melanoma microenvironment.
What's new?
New results reveal how an Chinese herbal medicine component acts against melanoma. Dioscin, a natural steroidal saponin, induces apoptosis in breast cancer as well as boosting production of pro‐inflammatory cytokines. These authors investigated the chemical's effect on connexin 43, a tumor suppressing protein found in the microenvironment that is frequently silenced in metastatic melanoma. Dioscin remarkably enhanced the expression of connexin 43, as well as boosting its ability to reverse the metastatic transition. Treatment with dioscin also enhanced the immune response, spurring macrophages to attack the tumor cells.
A transient three-dimensional mathematical model is developed to study the slag entrapment in a continuous-casting mold. The unsteady turbulent flow is computed using the large eddy simulation (LES). ...The sub-grid scale structure is modeled by Smagorinsky–Lilly model. The movements of discrete bubbles, as well as three continuous phases (air-slag-steel) are described by solving the coupled discrete particle model (DPM) and volume of fraction (VOF) model. Comparisons are made between the plant measurements and predicted result of level fluctuations near the submerged entry nozzle (SEN), and good agreements are obtained. Results reveal that the average velocity, transverse velocity of slag-metal interface are not accurate to evaluate the seriousness of slag entrapment in mold, because the surface velocity is also affected by bubble movements. By comparison, the variation trend of maximum velocity of slag-metal interface shows good agreements with that of the slag drops and therefore can be used to evaluate the slag entrapment in mold. Then considering interfacial tension force, mold size, impinging angle, port angle, impinging velocity and depth, a new dimensionless value of “
J
” is established to evaluate the seriousness of slag entrapment. Through comparing with traditional “
F
value”, the
J
value shows remarkable advantages in predicting slag entrapment in mold with different widths and volume flow rates of argon. The results are beneficial for controlling slag entrapment during continuous casting process.
Aconitine (AC) is the primary bioactive and secondary metabolite alkaloidin of Aconitum species which is accounted for more than 60% of the total diester-diterpenoid alkaloids in Aconite. To evaluate ...the analgesic effects of AC, 4 different pain models including hot plate assay, acetic acid writhing assay, formalin and CFA induced pain models were adopted in this study. In hot plate experiment, AC treatment at concentration of 0.3 mg/kg and 0.9 mg/kg improved the pain thresholds of mice similar to the positive drug aspirin at the concentration of 200 mg/kg (17.12% and 20.27% VS 19.21%). In acetic acid writhing experiment, AC significantly reduced the number of mice writhing events caused by acetic acid, and the inhibition rates were 68% and 76%. These results demonstrated that AC treatment revealed significant analgesic effects in both acute thermal stimulus pain model and chemically-induced visceral pain model. The biphasic nociceptive responses induced by formalin were significantly inhibited after AC treatment for 1h or 2h. The inhibition rates were 33.23% and 20.25% of AC treatment for 1h at 0.3 mg/kg and 0.9 mg/kg in phase I. In phase II, the inhibition rates of AC and aspirin were 36.08%, 32.48% and 48.82% respectively, which means AC showed similar analgesic effect to non-steroidal anti-inflammatory compounds. In the chronic CFA-induced nociception model, AC treatment also improved mice pain threshold to 131.33% at 0.3 mg/kg, which was similar to aspirin group (152.03%). Above all, our results verified that AC had obviously analgesic effects in different mice pain models.
This study aimed to clarify the efficacy and safety of Xinbao pill (XBP) as an adjunctive treatment for chronic heart failure (CHF).
Randomized controlled trials (RCTs) on the efficacy and safety of ...XBP in the treatment of CHF were searched from the six databases. The risk of bias assessment tool recommended by Cochrane Handbook 5.1 were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. The subgroup and sensitivity analyses were also performed. The grading recommendations assessment, development, and evaluation (GRADE) technique were used to assess the evidence's certainty.
Nine RCTs with a total of 882 patients were identified in this study. The meta-analysis demonstrated that XBP as adjunctive therapy was superior to conventional medicine alone for the treatment of CHF in improving the left ventricular ejection fraction (LVEF; MD = 5.34; 95% CI 4.68 to 5.99;
< 0.001), the total effective rate (RR = 1.21; 95% CI, 1.14 to 1.29;
< 0.001), the cardiac output (MD = 0.56; 95% CI 0.42 to 0.70;
< 0.001), the stroke volume (MD = 3.42; 95% CI 2.03 to 4.81;
< 0.001) and the 6-min walking distance (6-MWD; MD = 31.95; 95% CI 21.83 to 42.06;
< 0.001), meanwhile reducing the left ventricular end-diastolic diameter (LVEDD; MD = -3.22; 95% CI -4.03 to -2.42;
< 0.001) and left ventricular end-systolic dimension (LVESD; MD = -2.93; 95% CI -3.80 to -2.06;
< 0.001). Regarding safety, a total of 2.4% (11/456) adverse reactions occurred in the XBP groups while 3.9% (18/456) in the control group. The outcomes' evidentiary quality ranged from "very low" to "moderate".
This study indicated that XBP as adjunctive therapy combined with conventional medicine seemed to be safe and more effective than conventional medicine alone in treating CHF. However, due to the poor methodological quality of the included RCTs, further well-designed RCTs are required to confirm the efficacy and safety of XBP.
Ilex pubescens Hook. et Arn (MDQ), a traditional Chinese herb, is used in the treatment of cardiovascular diseases. However, the mechanisms underlying the preventive effect of MDQ on blood stasis ...remain unclear.
In this study, serum metabolomics integrated with a biochemical assay strategy were established to evaluate the preventive effect and mechanism of action of MDQ on rats with acute blood stasis.
Forty-nine rats were divided into seven groups: the control group, model group, aspirin treatment group (30 mg/kg), clopidogrel treatment group (8 mg/kg) and three MDQ treatment groups (250, 500 and 1000 mg/kg). A hybrid quadrupole time of flight mass spectrometry (QTOF/MS) coupled to ultra-high-performance liquid chromatography (UPLC) was applied for profiling the serum metabolites. The multivariate data analysis techniques using unsupervised principal component analysis (PCA) and supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used for pattern recognition and distinguishing variabilities among groups.
MDQ protected the rats against blood stasis, as evidenced by the restoration of the anti-platelet aggregation activity, fibrinogen concentration, prothrombin time, thrombin time, activated partial thromboplastin time, endothelial nitric oxide synthase, endothelin, thromboxane B2 and 6-keto-prostaglandin F1α. The combination of PCA and OPLS-DA revealed deviations in eighteen differential biomarkers in serum. The identified biomarkers were primarily engaged in the metabolic pathways including arachidonic acid metabolism, glycerophospholipid metabolism, phospholipid biosynthesis and bile acid biosynthesis. The levels of eleven biomarkers showed significant alterations and a tendency to be restored to normal values in MDQ-treated blood stasis rats. Moreover, a correlation network diagram was constructed to show the serum biomarkers perturbed by MDQ.
These results suggested that MDQ had preventive effects on blood stasis in rats via arachidonic acid metabolism and glycerophospholipid metabolism.
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Electromagnetic fields have emerged as powerful tools for addressing current problems in thin slab continuous casting processes in the iron and steel industry. Substantial studies have been ...undertaken on the fundamental effects of electromagnetic brakes (EMBr) and strand electromagnetic stirring (SEMS). However, little attention has been focused on melt flow and solidification in a thin slab continuous caster with the simultaneous application of an EMBr and SEMS. The present study aimed to predict transient fields in the caster using a large eddy simulation and an enthalpy-porosity method. The electric potential method was applied in the braking process, and the conductivity change with solidification was considered. The suppressive effect on the intensity of the nozzle jet, the balance effect on the mold flow, and a dispersion effect could be observed. The dispersion effect was a novel finding and was beneficial to a flatter nozzle jet. In contrast, SEMS caused a highly turbulent flow in the strand. A large vortex could be observed in the casting direction. The solidified shell became more uniform, and the solidification rate became obviously slower. These findings supported the view that a high-quality thin slab can be produced by the application of an EMBr and SEMS.
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