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Tridax procumbens (cotton buttons) is a flowering plant with a medicinal reputation for treating infections, wounds, diabetes, and liver and kidney diseases. The present research was conducted to evaluate the possible protective effects of the T. procumbens methanolic extract (TPME) on an experimentally induced type 2 diabetes rat model. Wistar rats with streptozotocin (STZ)-induced diabetes were randomly allocated into five groups of five animals each, viz., a normal glycemic group (I), diabetic rats receiving distilled water group (II), diabetic rats with 150 (III) and 300 mg/kg of TPME (IV) groups, and diabetic rats with 100 mg/kg metformin group (V). All treatments were administered for 21 consecutive days through oral gavage. Results: Administration of the T. procumbens extract to diabetic rats significantly restored alterations in levels of fasting blood glucose (FBG), body weight loss, serum and pancreatic insulin levels, and pancreatic histology. Furthermore, T. procumbens significantly attenuated the dyslipidemia (increased cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL) in diabetic rats), serum biochemical alterations (alanine transaminase (ALT), aspartate transaminase (AST), alanine phosphatase (ALP), blood urea nitrogen (BUN), creatinine, uric acid, and urea) and full blood count distortion in rats with STZ-induced diabetes. The TPME also improved the antioxidant status as evidenced by increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased malondialdehyde (MDA); and decreased levels of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), and proinflammatory mediators including nuclear factor (NF)-κB, cyclooxygenase (COX)- 2, and nitrogen oxide (NOx) in the brain of rats with STZ-induced diabetes compared to rats with STZ-induced diabetes that received distilled water. However, TPME treatment failed to attenuate the elevated monoamine oxidases and decreased dopamine levels in the brain of rats with STZ-induced diabetes. Extract characterization by liquid chromatography mass spectrometry (LC-MS) identified isorhamnetin (retention time (RT)= 3.69 min, 8.8%), bixin (RT: 25.06 min, 4.72%), and lupeol (RT: 25.25 min, 2.88%) as the three most abundant bioactive compounds that could be responsible for the bioactivity of the plant. In conclusion, the TPME can be considered a promising alternative therapeutic option for managing diabetic complications owing to its antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory effects in rats with STZ-prompted diabetes.

Background Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that has been found to induce matrix metalloproteinase-9 (MMP-9) activation and result in eventual retinal dysfunction. Proinflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β (IL-1β) were also found to be involved in disease progression by mediating MMP-9 production. We previously reported that fungal derivative theissenolactone C (LC53) could exert ocular protective effects by suppressing neuroinflammation in experimental uveitis. Purpose The aim of this study was to investigate the retinoprotective effects of natural compound LC53 on the high IOP-induced ischemia/reperfusion (I/R)-injury model of glaucoma and its cellular mechanisms. Methods A high IOP-induced I/R-injury model was manipulated by normal saline injection into the anterior chamber of the rat eye. MCP-1-stimulated monocytes and IL-1β-activated primary astrocytes were used to investigate the cellular mechanisms of LC53. Retinal function was evaluated with the scotopic threshold response (STR) and combined rod–cone response by electroretinography (ERG). As a positive control, rats were treated with memantine. MMP-9 gelatinolysis, mRNA expression and protein expression were analyzed by gelatin zymography, RT-PCR, and Western Blot, respectively. The phosphorylation levels of MAPKs and NF-κB p65 were tested by Western Blot. Additionally, the levels of inflammatory MCP-1 and IL-1β were determined by ELISA. Results The present study revealed that LC53 preserved the retina functional deficiency assessed by scotopic threshold response (STR) and combined rod–cone response of ERG after high IOP-induced I/R injury. These retinal protective effects of LC53 were positively correlated with inhibitory activities in I/R injury-elicited ocular MMP-9 activation and expression. The increased level of MCP-1 was not affected, and the enhanced IL-1β production was partially reduced by LC53 in the retina after I/R injury. According to cellular studies, LC53 significantly and concentration-dependently abrogated MMP-9 activation and expression in MCP-1-stimulated THP-1 monocytes. We found the inhibitory activities of LC53 were through the ERK- and NF-κB-dependent pathways. In addition, LC53 dramatically suppressed IL-1β-induced MMP-9 activation and expression in primary astrocytes. The phosphorylation of 65-kD protein (p65) of NF-κB was substantially blocked by LC53 in IL-1β-stimulated primary astrocytes. Conclusion LC53 exerted a retinal protective effect through NF-κB inhibition and was highly potent against MMP-9 activities after high IOP-induced I/R injury, suggesting that LC53 would be a promising drug lead for glaucoma or related medical conditions attributed to retinal ischemia.

In this study, diamond powder was incorporated into oxide layers formed on 6061 Al alloy by using plasma electrolytic oxidation (PEO) method. Diamond powder, 1.5 μm in average size, was added in an amount of 0, 3, 6 and 9 g/L, respectively, into the electrolyte containing 0.15 M Na2SiO3 and 0.16 M H3BO3. Phases, microstructure and composition of the oxide layers were investigated by XRD, SEM and EDX analyses. Micro-hardness of the coatings was measured using a micro-indenter. Corrosion performance of PEO coatings was evaluated using potentiodynamic polarization in a solution of 3.5% NaCl. Wear resistance was evaluated using a ball-on-disk tribometer. Both XRD and EDX spectra prove the incorporation of diamond into the coating. With increasing content of diamond powder in the electrolyte, analytical results indicate that the thickness, roughness, corrosion and wear resistance of the coatings increase. PEO coatings obtained with an optimum diamond powder content 6 g/L shows the best performance. The best corrosion resistance is 9.70 × 108 Ω cm2, the highest micro-hardness 855 HV, the lowest average friction coefficient 0.29, and showing the least weight and volume losses after wear tests. Performance of the coatings deteriorates when obtained at a higher content of added diamond powder, 9 g/L. This is due to the sudden increase of both porosity and roughness of the coatings. The variation in coating performance is explained based on the evolution of phase, microstructure, micro-hardness, porosity and roughness with the amount of diamond incorporation.

Micro-arc oxidation (MAO) has been an important surface treatment of Al alloys for surface hard-coating and corrosion protection. We used direct current (DC) as the power supply at a constant current density 10 A/dm 2 during 30-min MAO processing of 6061 Al alloy. The electrolyte bath contained 9.765 g/L Na 2 SiO 3 added with 10–60 mL/L ammonia water. With increasing added ammonia water in electrolyte bath, anomalous layer-thickening was observed reproducibly. Average coating thickness increases three times from 44 μm (no addition) to 135 μm (60 mL/L added). At 30 mL/L ammonia water micro-hardness of MAO layer maximizes at 1070 HV. X-ray diffraction shows the increasing intensity of amorphous phase accompanying with layer thickening. SEM analyses depict that size of surface micro-pore reduces with increasing added amount of ammonia water. Cross-sectional micrographs reveal micro-pores with a continuous coating-substrate interface. Elemental mapping and line-scans indicate uniform distribution of Al, O, Si and Na through the thickness of coating. Corrosion current density is plausibly improved to 6.41 × 10 −10 A/cm 2 by the addition of 60 mL/L ammonia water, whereas layer hardness is 840 HV. Anomalous thickening effect was not observed in case of surface layers micro-arc treated in ammonia water added electrolyte of sodium aluminate. In the later case no amorphous phase is observed in the MAO coating. The mechanism of anomalous thickening arises from the formation of amorphous surface-layer which entrapped large amount of solid debris formed during the discharging process and dispersing in electrolyte. The most significance of this highly corrosion-resistant thick and hard layer lies in the 66.7% energy budget when only 1/3 thickness is required.

Oxide layer was grown on 6061 Al alloy by micro arc oxidation (MAO) using a power supply of hybrid voltages: direct (V DC ) and alternative (V AC ) ones. The power supply was set at a fixed V AC voltage maintained at a value between 240 and 320 V coupled with an in-series V DC which is auto-tuned to keep the constant current density 5 A dm − 2 . This led to varying ratios of final V DC versus maximum V AC (V DC-final /V AC-max ) as the major processing parameter. Alkaline solution containing electrolytes of Na 2 SiO 3 , NaH 2 PO 2 ·H 2 O, and Na 2 WO 4 ·2H 2 O was used. All MAO samples show an oxide layer thickness around 10 μm after 30 min operation time. For samples MAO with V AC-max 320 V SEM morphology indicates a smoother oxide-layer surface with uniform micro-pores, which have mean diameters less than 1 μm. XRD patterns show the main oxide-phases of hexagonal α-Al 2 O 3 , cubic γ-Al 2 O 3 and mullite (Al 2 O 3 · n SiO 2 ). Micro-hardness of MAO samples increases from 960 HV (V AC 240 V) to 1480 HV (V AC 320 V). Corrosion resistance of the MAO layer is significantly improved with reducing V DC-final /V AC-max . Samples by V AC-max 320 V show the minimum corrosion current density 6.28 × 10 − 9 A cm − 2 , corresponding to the highest polarization resistance 2.20 × 10 8 Ω cm 2 . Comparing with MAO layers obtained by using V DC only, the oxide-layer by hybrid voltages is a little thinner, much harder and much more corrosion resistant.

Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Despite several antiviral drugs including interferon-α and nucleotide derivatives are approved for clinical treatment for HBV, critical issues remain unresolved, e.g., low-to-moderate efficacy, adverse side effects, and resistant strains. In this study, novel Paeonol-phenylsulfonyl derivatives were synthesized and their antiviral effect against HBV was evaluated. The experimental results indicated that these compounds process significant antiviral potential, including the inhibition of viral antigen expression and secretion, and the suppression of HBV viral DNA replication. Among compounds synthesized in this research, compound 2-acetyl-5-methoxyphenyl 4-methoxybenzenesulfonate (7f) had the most potent inhibitory activity with IC50 value of 0.36 μM, and high selectivity index, SI (TC50/IC50) 47.75; which exhibited an apparent inhibition effect on viral gene expression and viral propagation in cell culture model. So, we believe our compounds could serve as reservoir for antiviral drug development.

The compound LPRP-Et-97543 was isolated from Liriope platyphylla roots and was observed to have potential anti-viral effects in HepG2.2.15 cells against hepatitis B virus (HBV). The antiviral mode was further clarified, and the HBV-transfected Huh7 cells were used as the platform. During viral gene expression, LPRP-Et-97543 treatment had apparent effects on the viral precore/pregenomic and S/preS RNA. Promoter activity analysis demonstrated that LPRP-Et-97543 significantly reduced Core, S, and preS but not X promoter activities. Further examination showed that putative signaling pathways were involved in this inhibitory effect, indicating that NF-κB may serve a putative mediator of HBV gene regulation with LPRP-Et-97543. In addition, the nuclear expression of p65/p50 NF-κB member proteins was attenuated with LPRP-Et-97543 and augmented cytoplasmic IκBα protein levels but without affecting the expression of these proteins in HBV non-transfected cells during treatment. Moreover, LPRP-Et-97543 reduced the binding activity of NF-κB protein to CS1 element of HBV surface gene in a gel retardation analysis and inhibited CS1 containing promoter activity in HBV expressed cells. However, HBV transfection significantly enhances CS1 containing promoter activity without compound treatment in cells. Finally, transfection of the p65 expression plasmid significantly reversed the inhibitory effect of LPRP-Et-97543 on the replicated HBV DNA level in HBV positive cells. In conclusion, this study suggests that the mechanism of HBV inhibition by LPRP-Et-97543 may involve the feedback regulation of viral gene expression and viral DNA replication by HBV viral proteins, which interferes with the NF-κB signaling pathway.

Purpose This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

In this paper, the Petri net-based wireless sensor node architecture (PN-WSNA) is used to control a humanoid robot to play weightlifting and sprint games in the FIRA HuroCup league. With the PN-WSNA approach, the control scenario and decision-making for playing weightlifting and sprint games can be modeled as a PN-WSNA model. The PN-WSNA inference engine is further used to interpret and execute the PN-WSNA model according to the sensor information from visual perception. Therefore, the implementation of playing weightlifting and sprint games is achieved in terms of the PN-WSNA model instead of native code. To verify the PN-WSNA-based implementation approach, an autonomous humanoid robot equipped with a camera and a single-board computer is used for experiments, where the camera is responsible for grabbing image frames; the single-board computer is responsible for visual localization; and the PN-WSNA models the execution and locomotion command generation. Finally, several PN-WSNA models for playing weightlifting and sprint games are proposed and the experimental results are demonstrated and discussed to validate the feasibility of applying the proposed PN-WSNA-based implementation approach.

The compound p-hydroxyacetophenone (PHAP) isolated from Artemisia morrisonensis was found to have potential anti-HBV effects in HepG2 2.2.15 cells. We clarified its antiviral mode further and HBV-transfected Huh7 cells were used as the platform. During viral gene expression, treatment with PHAP had no apparent effects on the viral precore/pregenomic RNA. However, the 2.4-kb preS RNA of viral surface gene increased significantly relative to the 2.1-kb S RNA with PHAP. Promoter activity analysis demonstrated that PHAP had a potent effect on augmenting the viral preS promoter activity. The subsequent increase in the large surface protein and induce endoplasmic reticular (ER) stress has been reported previously. Interestingly, PHAP specifically reduced ER stress related GRP78 RNA/protein levels, but not those of GRP94, in treated Huh7 cells while PHAP also led to the significant intracellular accumulation of virus. Moreover, treatment with the ER chaperone inducer thapsigargin relieved the inhibitory effect of PHAP based on the supernatant HBV DNA levels of HBV-expressed cells. In conclusion, this study suggests that the mechanism of HBV inhibition by PHAP might involve the regulation of viral surface gene expression and block virion secretion by interference with the ER stress signaling pathway.

Over-expression of transcription factor nuclear factor-κB (NF-κB) in the residual tumor after the treatment is often observed at the later period of cancer radiotherapy, results in tumor radioresistance and poor treatment outcome. In this study, we combined sorafenib, a multikinase inhibitor, with ionizing radiation to evaluate the therapeutic effect, and to elucidate the possible mechanism responsible for the radiosensitization of sorafenib on a human HT29/tk-luc colorectal carcinoma in vitro and in vivo. Clonogenic survival and cell cycle analysis were used to evaluate the cytotoxicity of sorafenib in vitro. The combination effect and the role of NF-κB in therapeutic efficacy with respects in apoptosis and tumor cell invasion were studied with HT29/tk-luc tumor-bearing animal model. The expression of NF-κB and its downstream-related proteins were assayed with electrophoretic mobility shift assay (EMSA) and Western blot. Sorafenib combined with radiation shows the synergistic cytotoxicity on HT29/tk-luc cells and increased tumor cell apoptosis. Both EMSA and Western blot show that the NF-κB activity induced by radiation is significantly suppressed by sorafenib. Combination of sorafenib and radiation shows the maximum tumor growth inhibition as compared to that of sorafenib alone or radiation alone in vivo (P