Forsythoside A inhibits adhesion and migration of monocytes to type II alveolar epithelial cells in lipopolysaccharide-induced acute lung injury through upregulating miR-124.

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI.

Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study.

BACKGROUND: Thyroid hormones deeply influence the cardiovascular system; however, the association between the fT3/fT4 ratio and the clinical outcome in euthyroid patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) is not well defined. Therefore, the present study aimed to assess the prognostic performance of the fT3/fT4 ratio in predicting the long-term prognosis in euthyroid patients with AMI undergoing PCI. METHODS: In a prospective cohort study with a 1-year follow-up, according to the clinical end point, 953 euthyroid individuals (61.0 ± 11.6; female, 25.8%) were divided into two groups: (1) the survival group (n = 915) and (2) the death group (n = 38). RESULTS: According to Cox regression multivariate analysis, fT4 (HR: 1.249, 95% CI: 1.053-1.480, p = 0.010) and the fT3/fT4 ratio (HR: 3.546, 95% CI: 1.705-7.377, p = 0.001) were associated with an increased risk of 1-year all-cause mortality. The prognostic performance of the fT3/fT4 ratio was similar to the Global Registry of Acute Coronary Events (GRACE) score in predicting 1-year all-cause mortality (C-statistic: z = 0.261, p = 0.794; IDI: -0.017, p = 0.452; NRI: -0.049, p = 0.766), but better than fT4 (C-statistic: z = 2.438, p = 0.015; IDI: 0.053, p = 0.002; NRI: 0.656, p < 0.001). The fT3/fT4 ratio also significantly improved the prognostic performance of the GRACE score (GRACE score vs GRACE score + fT3/fT4 ratio: C-statistic: z = 2.116, p = 0.034; IDI: 0.0415, p = 0.007; NRI: 0.614, p < 0.001). CONCLUSIONS: In euthyroid patients with AMI undergoing PCI, the fT3/fT4 ratio was an independent predictor of 1-year all-cause mortality. Its prognostic performance was similar to the GRACE score, and also improved its prognostic performance (GRACE score vs GRACE score + fT3/fT4 ratio).

Predictive Value of Mean Platelet Volume/Platelet Count for Prognosis in Acute Myocardial Infarction.

Increased mean platelet volume (MPV) has been associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). We aim to assess whether MPV/platelet count (MPV/PC) ratio is a useful marker to predict long-term prognosis in patients with STEMI undergoing PCI. Moreover, the prognostic accuracy of MPV/PC ratio is compared with MPV. 962 consecutive patients with STEMI treated with P-PCI were considered. According to the admission MPV/PC values, the population was divided into two groups: high MPV/PC group (n = 320, MPV/PC ≥ 0.055) and low MPV/PC group (n = 642, MPV/PC < 0.055). Multivariate analysis showed that high MPV/PC was an independent predictor of major adverse cardiovascular event (MACE; hazard ratio [HR]: 1.121, 95% confidence interval [CI]: 1.056-1.190, P < 0.01), all-cause mortality (HR: 1.109, 95% CI: 1.016-1.209, P = 0.020), cardiac mortality (HR: 1.141, 95% CI: 1.038-1.253, P = 0.006), nonfatal myocardial reinfarction (HR: 1.148, 95% CI: 1.044-1.262, P = 0.004), and unplanned repeat revascularization (HR: 1.073, 95% CI: 1.007-1.144, P = 0.030), respectively. MPV/PC ratio has good accuracy for predicting MACE (the area under the receiver-operating characteristic curve: 0.764), and the cut-off value was 0.054 with a sensitivity of 0.813 and a specificity of 0.662. The discriminatory performance of MPV/PC ratio was better than MPV for predicting MACE (MPV/PC ratio versus MPV: z = 2.285, P = 0.022), in patients with STEMI undergoing P-PCI. MPV/PC ratio is able to but better than MPV to predict long-term adverse outcomes in patients with STEMI undergoing P-PCI.

Culprit-only versus staged complete revascularization for patients with ST-segment elevation myocardial infarction and Multivessel disease: a retrospective cohort study.

BACKGROUND: Multivessel disease (MVD) is common in patients with ST-segment elevation myocardial infarction (STEMI), but optimal treatment management remains undetermined. METHODS: In this retrospective cohort study, 602 consecutive STEMI patients with MVD were enrolled between January 1, 2010 and October 1, 2014. Three hundred and eighty-two patients underwent culprit-only revascularization and 220 underwent staged complete revascularization. Primary end points were a composite of cardiac mortality or nonfatal reinfarction. RESULTS: The mean duration of follow-up was 35 months (12-71 months). Following multivariate analysis, staged complete revascularization was associated with a lower rate of the composite of cardiac mortality or nonfatal reinfarction [HR: 0.430, 95 % CI: 0.197-0.940, P = 0.034] and unplanned repeat revascularization [HR: 0.343, 95 % CI: 0.166-0.708, P = 0.004] compared with culprit-only revascularization. CONCLUSIONS: Compared with culprit-only revascularization, staged complete revascularization significantly reduced the rate of the composite of cardiac mortality or nonfatal reinfarction, and the need for unplanned repeat revascularization.

[Brain function network analysis and recognition for psychogenic non-epileptic seizures based on resting state electroencephalogram].

Studies have shown that the clinical manifestation of patients with neuropsychiatric disorders might be related to the abnormal connectivity of brain functions. Psychogenic non-epileptic seizures (PNES) are different from the conventional epileptic seizures due to the lack of the expected electroencephalographically epileptic changes in central nervous system, but are related to the presence of significant psychological factors. Diagnosis of PNES remains challenging. We found in the present work that the connectivity between the frontal and parieto-occipital in PNES was weaker than that of the controls by using network analysis based on electroencephalogram (EEG) signals. In addition, PNES were recognized by using the network properties as linear discriminant nalysis (LDA) input and classification accuracy was 85%. This study may provide a feasible tool for clinical diagnosis of PNES.

The evolution law of deviatoric stress and asymmetric control technology in roadways during panel mining through overlying residual coal pillars.

Close-distance coal seams (CDCS) are widely distributed, and the layout of the upper and lower panels can be divided into "=" type and "+" type. The "+" superposition of upper and lower coal pillars in CDCS caused strong mine pressure, but there are few studies on the panel crossing residual coal pillars (RCP) when the upper and lower coal seams are "+" type layout. In view of the special spatial position ("+" type layout), this paper takes the typical panel 4-301 of a particular mine as the project indagation background and studies mining and crossing the overlying coal pillars by dint of field measurement, numerical simulation, indoor test, and engineering application. Compared with vertical stress or horizontal stress alone, the indexes of deviatoric stress and plastic zone can reflect the failure evolution of surrounding rock more comprehensively. Hence, this paper analyzes the expansion form of the plastic zone and the variation law of deviatoric stress before and after mining influence in the underlying mining roadway. The research results show that: (1) There is a sub-peak zone of deviatoric stress under the RCP. The deviatoric stress is bimodal in the range of 9 m below. After the peak value decays to 7.4 MPa, it changes to a single peak located in the area directly below the middle of the RCP. (2) The maximum plastic zones of the roof and two ribs of the roadway below the RCP are 3.4 m and 5 m, respectively. The crest value of deviatoric stress reaches 10 MPa. As the distance between the panel and the RCP decreases, the shape of the high deviatoric stress area presents the evolution law from the "ellipse" of the roof → the "crescent" of two ribs → the "cochlea" of the tips of the ribs. (3) When the mining of the underlying panel is 10 m, 0 m, or - 10 m away from the RCP (without passing through the RCP). The crest value of deviatoric stress within 5-10 m in advance of the roadway increases in turn. However, the peak value is significantly reduced when it is - 20 m away from the RCP (through the RCP). The crest value of deviatoric stress of two ribs decreases in turn along the panel rib → section coal pillar rib → solid coal rib. Based on this, the underlying 45 m of the RCP is divided into area I (10 m), area II (overlapping area 20 m), and area III (15 m) based on the degree of disturbance. And propose the technical scheme of asymmetric combined control in different zones by using asymmetric channel steel truss anchor cable for the top-ribs of areas I and III, and top-ribs asymmetric channel steel truss anchor cable + door-type support in area II. On-site project practice shows that the partitioned control technology successfully resisted the roadway instability and failure caused by the dynamic-static superimposed stress disturbance under the RCP and realized the primary support of the sectional coal roadway. The conclusion provides technical support and scheme design for the partitioning support of roadways under similar "+" type cross-panels.

Decoding polyphenol metabolism in patients with Crohn's disease: Insights from diet, gut microbiota, and metabolites.

Crohn's disease (CD) is a chronic and progressive inflammatory disease that can involve any part of the gastrointestinal tract. The protective role of dietary polyphenols has been documented in preclinical models of CD. Gut microbiota mediates the metabolism of polyphenols and affects their bioactivity and physiological functions. However, it remains elusive the capacity of microbial polyphenol metabolism in CD patients and healthy controls (HCs) along with its correlation with polyphenols intake and polyphenol-derived metabolites. Thus, we aimed to decode polyphenol metabolism in CD patients through aspects of diet, gut microbiota, and metabolites. Dietary intake analysis revealed that CD patients exhibited decreased intake of polyphenols. Using metagenomic data from two independent clinical cohorts (FAH-SYSU and PRISM), we quantified abundance of polyphenol degradation associated bacteria and functional genes in CD and HCs and observed a lower capacity of flavonoids degradation in gut microbiota residing in CD patients. Furthermore, through analysis of serum metabolites and enterotypes in participants of FAH-SYSU cohort, we observed that CD patients exhibited reduced levels of serum hippuric acid (HA), one of polyphenol-derived metabolites. HA level was higher in healthier enterotypes (characterized by dominance of Ruminococcaceae and Prevotellaceae, dominant by HCs) and positively correlated with multiple polyphenols intake and abundance of bacteria engaged in flavonoids degradation as well as short-chain fatty acid production, which could serve as a biomarker for effective polyphenol metabolism by the gut microbiota and a healthier gut microbial community structure. Overall, our findings provide a foundation for future work exploring the polyphenol-based or microbiota-targeted therapeutic strategies in CD.

Quassinoids from Eurycoma longifolia with antiviral activities by inhibiting dengue virus replication.

BACKGROUND: Dengue caused by dengue virus (DENV) spreads rapidly around the world. However, there are no worldwide licensed vaccines or specific antivirals to combat DENV infection. Quassinoids are the most characteristic components of Eurycoma longifolia, which have been reported to display a variety of biological activities. However, whether quassinoids exert anti-DENV activities remains unknown. PURPOSE: To test the quassinoids of E. longifolia for their activity against DENV and to clarify the potential mechanisms. METHODS: The quassinoids from E. longifolia were isolated by chromatography techniques, and their chemical structures were elucidated by spectroscopic analysis. The anti-DENV activities of quassinoids on baby hamster kidney cells BHK-21 were determined by lactate dehydrogenase (LDH) assay. The synthesis of progeny virus was measured by plaque assay. The expression levels of envelope protein (E) and non-structural protein 1 (NS1) were evaluated by qRT-PCR, Western blot and immunofluorescence assays. Molecular docking was used to screen the potential targets of the most active quassinoid against DENV-2, and surface plasmon resonance analysis was employed to confirm the direct binding between the most active quassinoid and potential target. RESULTS: Twenty-four quassinoids, including three new quassinoids (1 - 3), were isolated from the ethanol extract of E. longifolia. Quassinoids 4, 5, 9, 11, 12, 15, 16, 17, 19 and 20 significantly reduced the LDH release at the stages of viral binding and entry or intracellular replication. Among them, 19 (6α-hydroxyeurycomalactone, 6α-HEL) exhibited the best anti-DENV-2 activities with an EC50 value of 0.39 ± 0.02 µM. Further experiments suggested that 6α-HEL remarkably inhibited progeny virus synthesis and mRNA and protein expression levels of E and NS1 of DENV-2. Time-of-drug-addition assay suggested that 6α-HEL inhibited intracellular replication of DENV-2 at an early stage. Moreover, 6α-HEL was shown to interact with NS5-RdRp domain at a binding affinity of -8.15 kcal/mol. SPR assay further verified 6α-HEL bound to RdRp protein with an equilibrium dissociation constant of 1.49 × 10-7 M. CONCLUSION: Ten quassinoids from E. longifolia showed anti-DENV activities at processes of virus binding and entry or intracellular replication. The most active quassinoid 6α-HEL exerts the anti-DENV-2 activities at intracellular replication stage by directly targeting the NS5-RdRp protein. These results suggest that 6α-HEL could be a promising candidate for the treatment of DENV-2 infection.

Identification of an effective fraction from Ampelopsis Radix with anti-dengue virus activities in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue virus (DENV) infection is a global public health issue without effective therapeutic interventions. Chinese medicine with heat-clearing and detoxifying properties has been frequently used in the treatment of viral infection. Ampelopsis Radix (AR) is a traditional Chinese medicine for clearing heat and detoxification that has been widely used in the prevention and treatment of infectious diseases. However, no studies on the effects of AR against viral infection have been reported, thus far. AIM OF THE STUDY: To explore the anti-DENV activities of the fraction (AR-1) obtained from AR both in vitro and in vivo. MATERIALS AND METHODS: The chemical composition of AR-1 was identified by liquid chromatography-tandem MS (LC‒MS/MS). The antiviral activities of AR-1 were studied in baby hamster kidney fibroblast BHK-21 cells, ICR suckling mice and induction of interferon α/ß (IFN-α/ß) and IFN-γ R-/- (AG129) mice. RESULTS: Based on LC‒MS/MS analysis, 60 compounds (including flavonoids, phenols, anthraquinones, alkaloids and other types) were tentatively characterized from AR-1. AR-1 inhibited the cytopathic effect, the production of progeny virus and the synthesis of viral RNA and proteins by blocking DENV-2 binding to BHK-21 cells. Moreover, AR-1 significantly attenuated weight loss, decreased clinical scores and prolonged the survival of DENV-infected ICR suckling mice. Critically, the viral load in blood, brain and kidney tissues and the pathological changes in brain were remarkably alleviated after AR-1 treatment. Further study on AG129 mice showed that AR-1 obviously improved the clinical manifestations and survival rate, reduced viremia, attenuated gastric distension and relieved the pathological lesions caused by DENV. CONCLUSIONS: In summary, this is the first report that AR-1 exhibits anti-DENV effects both in vitro and in vivo, which suggests that AR-1 may be developed as a therapeutic candidate against DENV infection.

The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification.

Background: IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method: We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result: A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. Conclusion: This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.

N-Butanol Extract of Glycyrrhizae Radix et Rhizoma Inhibits Dengue Virus through Targeting Envelope Protein.

BACKGROUND: At present, about half of the world's population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n-butanol extract from Glycyrrhizae Radix et Rhizome (GRE). METHODS: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo. RESULTS: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice. CONCLUSIONS: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.

Protective effect of polysaccharides isolated from the seeds of Cuscuta chinensis Lam. on 5-fluorouracil-induced intestinal mucositis in mice.

PURPOSE: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. METHODS: PCCL was orally administered at a dose of 20 mg·kg-1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg-1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. RESULTS: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. CONCLUSIONS: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.

Anti-inflammatory, anti-angiogenetic and antiviral activities of dammarane-type triterpenoid saponins from the roots of Panax notoginseng.

Panax notoginseng has been used both as a traditional medicine and as a functional food for hundreds of years in Asia. However, the active constituents from P. notoginseng and their pharmacologic properties still need to be further explored. In this study, one new dammarane-type triterpenoid saponin (1), along with fourteen known analogs (2-15) were isolated and identified from the roots of P. notoginseng. The anti-inflammatory, anti-angiogenetic and anti-dengue virus effects of these isolated compounds were further evaluated. Compounds 1, 3, 5-7 and 10-12 exerted anti-inflammatory effects in two different zebrafish inflammatory models. Among them, 11, with the most significant activities, alleviated the inflammatory response by blocking the MyD88/NF-κB and STAT3 pathways. Moreover, compound 15 showed anti-angiogenetic activities in Tg(fli1:EGFP) and Tg(flk1:GFP) zebrafish, while 3 and 5 only inhibited angiogenesis in Tg(fli1:EGFP) zebrafish. Additionally, compounds 1, 3, 6, 8, 9 and 12 suppressed the replication of dengue virus either at the viral adsorption and entry stages or at the intracellular replication step. In conclusion, these findings enrich knowledge of the diversity of saponins in P. notoginseng and suggest that the dammarane-type triterpenoid saponins from P. notoginseng may be developed as potential functional foods to treat inflammation, angiogenesis or dengue-related diseases.

Emodin Protects Against Lipopolysaccharide-Induced Acute Lung Injury via the JNK/Nur77/c-Jun Signaling Pathway.

Background: Acute lung injury (ALI) is a serious inflammatory disease with clinical manifestations of hypoxemia and respiratory failure. Presently, there is no effective treatment of ALI. Although emodin from Rheum palmatum L. exerts anti-ALI properties, the underlying mechanisms have not been fully explored. Purpose: This study aimed to investigate the therapeutic effect and mechanism of emodin on LPS-induced ALI in mice. Methods: RAW264.7 cells and zebrafish larvae were stimulated by LPS to establish inflammatory models. The anti-inflammatory effect of emodin was assessed by ELISA, flow cytometric analysis, and survival analysis. In vitro mechanisms were explored by using Western blotting, luciferase assay, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) approach. The acute lung injury model in mice was established by the intratracheal administration of LPS, and the underlying mechanisms were assessed by detecting changes in histopathological and inflammatory markers and Western blotting in lung tissues. Results: Emodin inhibited the inflammatory factor production and oxidative stress in RAW264.7 cells, and prolonged the survival of zebrafish larvae after LPS stimulation. Emodin suppressed the expression levels of phosphorylated JNK at Thr183/tyr182 and phosphorylated Nur77 at Ser351 and c-Jun, and increased the expression level of Nur77 in LPS-stimulated RAW264.7 cells, while these regulatory effects of emodin on Nur77/c-Jun were counteracted by JNK activators. The overexpression of JNK dampened the emodin-mediated increase in Nur77 luciferase activity and Nur77 expression. Moreover, the inhibitory effect of emodin on c-Jun can be attenuated by Nur77 siRNA. Furthermore, emodin alleviated LPS-induced ALI in mice through the regulation of the JNK/Nur77/c-Jun pathway. Conclusions: Emodin protects against LPS-induced ALI through regulation on JNK/Nur77/c-Jun signaling. Our results indicate the potential of emodin in the treatment of ALI.

Sheng-Mai Yin exerts anti-inflammatory effects on RAW 264.7 cells and zebrafish.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-Mai Yin (SMY), a famous traditional Chinese medicine formula, has been commonly used in China for centuries to treat various diseases, such as inflammation-related diseases. However, the anti-inflammatory activity of SMY and its potential mechanisms still have not yet been clearly understood. AIM OF THE STUDY: In this study, we aimed to determine the anti-inflammatory effect of SMY and explore its underlying mechanisms both on RAW 264.7 cells and zebrafish. MATERIALS AND METHODS: The levels of pro-inflammatory cytokines IL-6 and TNF-α secreted by RAW 264.7 cells were measured by ELISA. The protein expressions of IκBα, p-IκBα (Ser32), STAT3 and p-STAT3 (Tyr705) were determined by Western blotting. And the nuclear translocation of NF-κB p65 in LPS-induced RAW 264.7 macrophage cells was detected by confocal microscopy. Moreover, the in vivo anti-inflammatory effect of SMY and its potential mechanisms were further investigated by survival analysis, hematoxylin-eosin staining (H&E), observation of neutrophil migration and quantitative real-time PCR (qRT-PCR) analysis in zebrafish inflammatory models. RESULTS: SMY reduced the release of IL-6 and TNF-α, inhibited the phosphorylation of IκBα and STAT3 as well as the nuclear translocation of NF-κB p65 in LPS-induced RAW 264.7 cells. Furthermore, the increased survival, decreased infiltration of inflammatory cells and the attenuated migration of neutrophils together suggested the in vivo anti-inflammatory effects of SMY. More importantly, SMY reduced the gene expressions of pro-inflammatory cytokines and suppressed LPS-induced up-regulation of NF-κB, IκBα and STAT3 in zebrafish inflammatory models. CONCLUSION: SMY exerts significant anti-inflammatory effects with a potential mechanism of inhibiting the NF-κB and STAT3 signal pathways. Our findings suggest a scientific rationale of SMY to treat inflammatory diseases in clinic.

Optimal combination of anti-inflammatory components from Chinese medicinal formula Liang-Ge-San.

ETHNOPHARMACOLOGICAL RELEVANCE: Liang-Ge-San (LGS), a traditional Chinese medicine (TCM) formula, is usually used in acute inflammatory diseases in China. AIM OF THE STUDY: This study aims to detect the optimal combination of anti-inflammatory components from LGS. MATERIALS AND METHODS: Four mainly representative components (phillyrin, emodin, baicalin, and liquiritin) from LGS were chosen. The optimal combination was investigated by orthogonal design study. Zebrafish inflammation model was established by lipopolysaccharide (LPS)-yolk microinjection, and then the anti-inflammatory activities of different combinations were determined by survival analysis, changes on inflammatory cells infiltration, the MyD88/NF-κB and MAPK pathways and inflammatory cytokines production. RESULTS: The different combinations of bioactive ingredients from LGS significantly protected zebrafish from LPS-induced inflammation, as evidenced by decreased recruitment of macrophages and neutrophils, inhibition of the MyD88/NF-κB and MAPK pathways and down-regulation of TNF-α and IL-6. Among them, the combination group 8 most significantly protected against LPS. The combination of group 8 is: 0.1 µM of emodin, 2 µM of baicalin, 20 µM of phillyrin and 12.5 µM of liquiritin. CONCLUSION: The optimized combination group 8 exerts the most significant anti-inflammatory activity by inhibiting the recruitment of inflammatory cells, activation of the MyD88/NF-κB and MAPK pathways and the secretion of pro-inflammatory cytokines. This present study provides pharmacological evidences for the further development of new modern Chinese drug from LGS to treat acute inflammatory diseases, but indicated the use of zebrafish in the screening of components from formulas.

Identification of Genetic Biomarkers for Diagnosis of Myocardial Infarction Compared with Angina Patients.

BACKGROUND: Myocardial infarction (MI) is the most terrible appearance of cardiovascular disease. The incidence of heart failure, one of the complications of MI, has increased in the past few decades. Therefore, the identification of MI from angina patients and the determination of new diagnoses and therapies of MI are increasingly important. The present study was aimed at identifying differentially expressed genes and miRNAs as biomarkers for the clinical and prognosis factors of MI compared with angina using microarray data analysis. METHODS: Differentially expressed miRNAs and genes were manifested by GEO2R. The biological function of differentially expressed genes (DEGs) was examined by GO and KEGG. The construction of a protein-protein network was explored by STRING. cytoHubba was utilized to screen hub genes. Analysis of miRNA-gene pairs was executed by the miRWalk 3.0 database. The miRNA-target pairs overlapped with hub genes were seen as key genes. Logistic regressive analysis was performed by SPSS. RESULTS: A number of 779 DEGs were recorded. The biological function containing extracellular components, signaling pathways, and cell adhesion was enriched. Twenty-four hub genes and three differentially expressed miRNAs were noted. Eight key genes were demonstrated, and 6 out of these 8 key genes were significantly related to clinical and prognosis factors following MI. CONCLUSIONS: CALCA, CDK6, MDM2, NRXN1, SOCS3, VEGFA, SMAD4, NCAM1, and hsa-miR-127-5p were thought to be potential diagnosis biomarkers for MI. Meanwhile, CALCA, CDK6, NRXN1, SMAD4, SOCS3, and NCAM1 were further identified to be potential diagnosis and therapy targets for MI.

Holistic quality evaluation of Qingwen Baidu Decoction and its anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingwen Baidu Decoction (QBD), a famous traditional Chinese medicine prescription with heat-clearing and detoxifying efficacies, is widely used in the treatment of inflammatory diseases. However, due to lack of holistic quality evaluation research, the further study on the detailed molecular mechanisms of action are still insufficient. AIM OF THE STUDY: This study aimed to evaluate the overall quality of QBD and to explore the anti-inflammatory effects and associated intracellular signaling pathways. MATERIALS AND METHODS: a comprehensive method of chemical fingerprint analysis and simultaneous multi-component quantification was firstly developed by high performance liquid chromatography with diode array detector (HPLC-DAD). Similarity analysis, principal component analysis and hierarchical cluster analysis with heatmap were also applied to screen out the markers components in QBD samples. Moreover, its anti-inflammatory effects and mechanisms were further investigated by survival analysis, hematoxylin-eosin staining (H&E), neutrophil observation, quantitative real-time PCR analysis (qRT-PCR), Western blotting and confocal microscopy. RESULTS: Twenty-one characteristic peaks from 11 herbs were chemically identified in the chromatographic fingerprint. Fifteen quantitative markers from 11 herbs, such as baicalin, wogonoside, geniposidic acid, oxypaeoniflora and so on, were screened out with the aid of chemometrics to further quantitatively assess the quality of QBD. The results of survival analysis, H&E and neutrophil observation in zebrafish inflammatory models consistently showed that QBD exerts potent anti-inflammatory effects in a dose-dependent manner. Additionally, QBD inhibited the activation of NF-κB and STAT3 signal pathways in LPS-induced zebrafish and RAW 264.7 macrophage cells. CONCLUSION: Collectively, our investigations firstly described the chemical profile of QBD and its possible mechanism of anti-inflammation, which provides a preferred strategy for monitoring the overall quality of QBD and supports its clinical application in treating inflammation-related diseases.

[Mechanism of Shenbing decoction â ¢ in the treatment of proteinuria in chronic kidney disease: a network pharmacology-based study].

OBJECTIVE: To identify the main active components in Shenbing decoction Ⅲ and their targets and explore the mechanism by which Shenbing decoction Ⅲ alleviates proteinuria in chronic kidney disease (CKD) based on network pharmacology. METHODS: The active components of Shenbing decoction Ⅲ and their potential targets, along with the oral bioavailability and drug-like properties of each component were searched in the TCMSP database. The proteinuria-related targets were searched in the GeneCards database. The active component-target network was constructed using Cytoscape software, and the acquired information of the targets from ClueGO was used for enrichment analysis of the gene pathways. RESULTS: A total of 102 active components were identified from Shenbing decoction Ⅲ. These active components acted on 126 targets, among which 69 were related to proteinuria. Enrichment analysis revealed fluid shear stress- and atherosclerosisrelated pathways as the highly significant pathways in proteinuria associated with CKD. CONCLUSIONS: We preliminarily validated the prescription of Shenbing decoction Ⅲ and obtained scientific evidence that supported its use for treatment of proteinuria in CKD. The findings in this study provide a theoretical basis for further study of the mechanism of Shenbing decoction Ⅲ in the treatment of proteinuria in CKD.