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Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of pro-inflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10−9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

Objective: To investigate the potential mechanisms of the protective effects of Buyang Huanwu decoction (BYHWD) on cardiomyocyte apoptosis after myocardial infarction (MI) and to provide the foundation for the clinical application of BYHWD in preventing and treating cardiomyocyte apoptosis-related disorders after MI. Methods: The MI rat model was established by ligation of the left anterior descending (LAD) coronary artery. After the 20-week treatment with BYHWD, the following parameters were assessed to investigate the protective effects of BYHWD on cardiomyocyte apoptosis after MI, both in vivo and in vitro: mortality rate; heart weight/body weight (HW/BW); transthoracic echocardiography measurements; histopathological analysis; immunohistochemistry (IHC) analysis; TUNEL apoptosis assay; caspase-3 activity assay; aldehyde dehydrogenase-2 (ALDH2) enzymatic activity assay; malondialdehyde (MDA) content analysis; western blot analysis; MTT assay; and Hoechst 33342/PI apoptosis assay. Results: The mortality of the MI rats was significantly reduced by BYHWD treatment. Furthermore, BYHWD treatment significantly improved the heart function and significantly reduced the HW/BW ratio. Histopathological analysis showed that BYHWD treatment significantly relieved MI-induced cardiac injury and significantly decreased collagen formation. The TUNEL apoptosis assay showed that treatment with BYHWD reduced the cardiomyocyte apoptosis of MI rats in a dose-dependent manner. Moreover, BYHWD treatment could significantly inhibit oxidative stress-induced neonatal cardiomyocyte apoptosis, which is consistent with the results of animal experiments in vivo. Interestingly, the ALDH2 activity and protein expression was significantly reduced in the MI model group, while the content of toxic aldehydes, including 4-HNE and MDA, was increased. Importantly, BYHWD enhanced the activity of ALDH2 and the expression of ALDH2 protein and attenuated the content of toxic aldehydes in a dose-dependent manner. Furthermore, we found that co-treatment with an ALDH2 inhibitor, disulfiram, partially inhibited the cardiomyocyte protective effects of BYHWD. Conclusions: Collectively, our results suggest that BYHWD exerted anti-apoptotic effects in cardiomyocytes after MI by enhancing the ALDH2 activity and protein expression and decreasing the toxic aldehyde content.

Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2′,4,4′-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.

Rhododendron micranthum Turcz., Rhododendron capitatum Maxim., Rhododendron dauricum L. and Rhododendron schlippenbachii Maxim. are four species of Rhododendron with the same geographical distribution, mainly distributed in the northeast of China and abundant in sources. This paper is the first comprehensive review on the chemical composition and pharmacological activities of these four species. The review, showed 323 compounds including terpenoids, flavonoids, coumarins, lignans, and volatile components were found in the four plants, and these four plants of Rhododendron not only had many chemical constituents of novel structures but also possessed extensive pharmacological effects, such as insecticide, analgesic, antibacterial, antitumor and so on. These research papers and literatures about the four plants were carried out using resources including classic books about Chinese herbal medicine, Flora Reipublicae Popularis Sinicae, and scientific databases including Web of Science, Sci-Finder, CNKI, Pubmed, etc. In recent years, our research group has engaged in the study of chemical composition and pharmacological activities of Rhododendron plants. The terpenes and volatile components isolated from Rhododendron plants contributed greatly to insecticidal activity. Therefore, it is of great significance to review researches of the four endemic resource-rich Rhododendron plants to help make full use of them especially on plant-derived insecticide. This comprehensive review will be significant for the discovery of new bioactive compounds from the above four endemic plants and will be informative for researchers seeking for new pharmacological activity of the four species.

Abstract Background DD was found to be associated with acute myocardial infarction (AMI) and renal insufficiency. However, it is uncertain whether DD is an independent risk factor of CI-AKI in patients undergoing pPCI. Methods We prospectively enrolled 550 consecutive patients with STEMI undergoing pPCI between January 2012 and December 2016. The predictive value of admission DD for CI-AKI was assessed by receiver operating characteristic (ROC) and multivariable logistic regression analysis. CI-AKI was defined as an absolute serum creatinine increase ≥0.3 mg/dl or a relative increase in serum creatinine ≥50% within 48 h of contrast medium exposure. Results Overall, the incidence of CI-AKI was 13.1%. The ROC analysis showed that the cutoff point of DD was 0.69 μg/ml for predicting CI-AKI with a sensitivity of 77.8% and a specificity of 57.3%. The predictive value of DD was similar to the Mehran score for CI-AKI (AUCDD = 0.729 vs AUCMehran = 0.722; p = 0.8298). Multivariate logistic regression analysis indicated that DD > 0.69 μg/ml was an independent predictor of CI-AKI (odds ratio [OR] = 3.37,95% CI:1.80–6.33, p 0.69 μg/ml was associated with an increased risk of long-term mortality during a mean follow-up period of 16 months (hazard ratio = 3.41, 95%CI:1.4–8.03, p = 0.005). Conclusion Admission DD > 0.69 μg/ml was a significant and independent predictor of CI-AKI and long-term mortality in patients undergoing pPCI.

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486–0.801; adjusted HR = 0.011, 95% CI = 0.002–0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731–0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.

Cardiovascular disease, a disease caused by many pathogenic factors, is one of the most common causes of death worldwide, and oxidative stress plays a major role in its pathophysiology. Tanshinone I (Tan I), a natural compound with cardiovascular protective effects, is one of the main active compounds extracted from Salvia miltiorrhiza. Here, we investigated whether Tan I could attenuate oxidative stress and oxidative stress–induced cardiomyocyte apoptosis through Nrf2/MAPK signaling in vivo and in vitro. We found that Tan I treatment protected cardiomyocytes against oxidative stress and oxidative stress–induced apoptosis, based on the detection of relevant oxidation indexes such as reactive oxygen species, superoxide dismutase, malondialdehyde, and apoptosis, including cell viability and apoptosis-related protein expression. We further examined the mechanisms underlying these effects, determining that Tan I activated nuclear factor erythroid 2 (NFE2)–related factor 2 (Nrf2) transcription into the nucleus and dose-dependently promoted the expression of Nrf2, while inhibiting MAPK signaling activation, including P38 MAPK, SAPK/JNK, and ERK1/2. Nrf2 inhibitors in H9C2 cells and Nrf2 knockout mice demonstrated aggravated oxidative stress and oxidative stress–induced cardiomyocyte injury; Tan I treatment suppressed these effects in H9C2 cells; however, its protective effect was inhibited in Nrf2 knockout mice. Additionally, the analysis of surface plasmon resonance demonstrated that Tan I could directly target Nrf2 and act as a potential Nrf2 agonist. Collectively, these data strongly indicated that Tan I might inhibit oxidative stress and oxidative stress–induced cardiomyocyte injury through modulation of Nrf2 signaling, thus supporting the potential therapeutic application of Tan I for oxidative stress–induced CVDs.

Background: Oxidative stress-induced apoptosis plays an important role in the development of heart failure. 3,5-Dicaffeoylquinic acid (3,5-diCQA), a phenolic compound, has shown protective effects against oxidative stress in many diseases. Objective: The objective of this study was to investigate the anti-apoptosis potential of 3,5-diCQA in cardiomyocyte cells under oxidative stress and explore its underlying mechanisms. Design: A model of tert-butyl hydroperoxide (TBHP)-induced apoptosis in a cardiomyocyte cell line (H9C2) was established. Cell viabilities on cell lines were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. The apoptosis was measured by hoechst33342 and propidium iodide (PI) fluorescent staining. PI (in red) stained the regions of cell apoptosis; Hoechet33342 (in blue) stained the nuclei. The Western blot was used to determine the expressions of related proteins such as p-PI3K: phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated Serine and Threonine kinase AKT (p-AKT), p-PTEN, Bcl-2, Bax, and caspase-3. Afterward, a PI3K inhibitor, LY294002, was applied to confirm the influence of the PI3K/Akt pathway on TBHP-treated cells of 3,5-diCQA. Then, H9C2 cells were pre-incubated with 3,5-diCQA alone to determine if the expression of activated PI3K/Akt signaling was mediated by 3,5-diCQA in H9C2 cells. Results: The results showed that TBHP resulted in an increase in cardiomyocyte apoptosis, whereas 3,5-diCQA treatment protected cells from TBHP-induced apoptosis in a dose-dependent manner. Moreover, 3,5-diCQA decreased expressions of Bax and caspase-3 but increased the phosphorylation levels of PI3K and Akt in TBHP-treated cells, which are the key molecules mediating cell survival, whereas phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphorylation was unchanged. Importantly, pre-incubation with a PI3K inhibitor (LY294002) partly abolished the anti-apoptosis effects of 3,5-diCQA. Further, 3,5-diCQA enhanced the phosphorylation levels of PI3K and Akt in H9C2 cells directly, while LY294002 attenuated the effects of 3,5-diCQA on PI3K and Akt. Conclusion: This study suggested that 3,5-diCQA rescued myocardium from apoptosis by increasing the activation of the PI3K/Akt signaling pathway.

Abstract In this paper, a laterally coupled distributed feedback (LC-DFB) laser based on modulation p-doped multiple InAs/GaAs quantum dot (QD) structures has been fabricated. The device exhibits a high side-mode suppression ratio (SMSR) of > 47 dB and a high thermal stability of dλ/dT = 0.092 nm/K under continuous-wave (CW) operation, which is mainly attributed to the high material gain prepared by modulation p-doping and rapid thermal annealing (RTA) process, and the significantly reduced waveguide losses by shallow-etched gratings and its close proximity to the laser ridge feature in the LC-DFB laser. With this superior performance of the DFB laser, the wide tunable dual-wavelength lasing operation has been obtained by delicately defining different periods for the grating structures on the two sides of the laser ridge or combining the reduced laser cavity length. The wavelength spacing between the two lasing modes can be flexibly tuned in a very wide range from 0.5 to 73.4 nm, corresponding to the frequency difference from 0.10 to 14 THz, which is the largest tuning range by the utilization of single device and hence providing a new opportunity towards the generation of CW THz radiation.

Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD.Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age- and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group.Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients.Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.

Abstract Background This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20–39 years old. Methods All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity. Results Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as

The microstructures evolution of precipitations for an ultra-low iron Alloy 625 subjected to long term aging treatment at 750°C was investigated using scanning electron microscope (SEM) and X-ray diffraction (XRD). The intergranular corrosion behaviors of Alloy 625 were evaluated by using ASTM G28A. The result shows that the precipitated phase γ′′-Ni3Nb was mainly precipitated at the grain boundaries and twin boundaries. The number and volume fraction of γ′′ increased with the prolonging of aging time. The transformation of γ′′ to δ-Ni3Nb occurred after aging periods of 200 h. The corrosion resistance of Alloy 625 was significantly reduced during aging treatment. The decrease in intergranular corrosion resistance of Alloy 625 was attributed to the dissolution of precipitated phase and chromium depleted zone. The mass loss rate of Alloy 625 after aging treatment is related to the volume of precipitated phase and can be simulated by Johnson-Mehl-Avrami equation.

Vascular smooth muscle cell (VSMC) proliferation and migration play a critical role in the development of arterial remodeling during various vascular diseases including atherosclerosis, hypertension, and related diseases. Luteolin is a food-derived flavonoid that exerts protective effects on cardiovascular diseases. Here, we investigated whether transforming growth factor-β receptor 1 (TGFBR1) signaling underlies the inhibitory effects of luteolin on VSMC proliferation and migration. We found that luteolin reduced the proliferation and migration of VSMCs, specifically A7r5 and HASMC cells, in a dose-dependent manner, based on MTS and EdU, and Transwell and wound healing assays, respectively. We also demonstrated that it inhibited the expression of proliferation-related proteins including PCNA and Cyclin D1, as well as the migration-related proteins MMP2 and MMP9, in a dose-dependent manner by western blotting. In addition, luteolin dose-dependently inhibited the phosphorylation of TGFBR1, Smad2, and Smad3. Notably, adenovirus-mediated overexpression of TGFBR1 enhanced TGFBR1, Smad2, and Smad3 activation in VSMCs and partially blocked the inhibitory effect of luteolin on TGFBR1, Smad2, and Smad3. Moreover, overexpression of TGFBR1 rescued the inhibitory effects of luteolin on the proliferation and migration of VSMCs. Additionally, molecular docking showed that this compound could dock onto an agonist binding site of TGFBR1, and that the binding energy between luteolin and TGFBR1 was -10.194 kcal/mol. Simulations of molecular dynamics showed that TGFBR1-luteolin binding was stable. Collectively, these data demonstrated that luteolin might inhibit VSMC proliferation and migration by suppressing TGFBR1 signaling.

BACKGROUND: To study the long-term effects of low-dosage strontium-90 (Sr90) irradiation on the recurrence of pterygium. METHODOLOGY/PRINCIPAL FINDINGS: One hundred twenty eyes from 104 patients with primary or recurrent pterygia were treated with surgery followed by Sr90 irradiation. In brief, starting on the sixth day after surgery, patients were treated with irradiation three times every other day at a total combined dosage of 2000 cGy to 3000 cGy. Corneal topography was used to evaluate ocular surface regularity before and after treatment. Patient follow-up was performed 2 days, 5 days, 2 weeks, 1 month, 3 months, 1 year, 5 years, and 10 years after surgery. Recurrence of pterygium was not observed in any of the patients in this study. Obvious cataract progression was observed in 6 eyes, which may be due to aging. During follow-up studies, only one eye was reported with dryness and foreign-body sensation. Significant pterygium-induced astigmatism was observed in corneal topography, which decreased after surgery. CONCLUSIONS/SIGNIFICANCE: Sr90 irradiation is effective in preventing the recurrence of primary and recurrent pterygia. We recommend delivering a total combined dosage of 2000 cGy to 3000 cGy of Sr90 irradiation administered in three batches every other day starting from the sixth day after surgery. Surgery is important in the rapid recovery of the cornea from pterygium-induced astigmatism.

BACKGROUND:Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. METHODS:83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose. RESULTS:Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells. CONCLUSIONS:Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2.

The crystal structure of the title compound in the paper by Sui, Fang, Luo, Chen & Zhou [Acta Cryst. (2006), E62, m1994–m1996] has been rerefined to allow for identification of a disordered dimethyl sulfoxide ligand.