Effects of epigallocatechin-3-gallate on the HMGB1/RAGE pathway in PM2.5-exposed asthmatic rats.

Current studies have shown that long-term exposure to fine particulate matter (PM2.5) can aggravate lung injury in asthmatic children. The HMGB1/RAGE pathway may play an important role, but few studies on the HMGB1/RAGE signaling pathway in PM2.5-induced asthma have been performed. Epigallocatechin-3-gallate (EGCG), which has antioxidant, anti-inflammatory and immunomodulatory effects, has not been examined in studies at home and abroad. In this study, we established an animal model of asthma and observed that the lung tissue was damaged, inflammatory cells infiltrated, bronchial wall thickness (WTt) and bronchial smooth muscle thickness (WTm) increased and the HMGB1 and RAGE mRNA and protein expression increased. The asthmatic rats exposed to PM2.5 showed significantly increased lung injury and inflammatory cell infiltration, WTt and WTm further increased, and HMGB1 and RAGE mRNA and protein levels were higher than those in the asthma group. The asthmatic rats exposed to PM2.5 were treated with EGCG, which alleviated the lung injury, reduced the number of inflammatory cells, decreased WTt and WTm, and reduced the expression of HMGB1 and RAGE mRNA and protein. The high-dose group showed more significant effects than the other groups. In conclusion, our results suggest that HMGB1 and RAGE are involved in the pathogenesis of asthma. PM2.5 exposure significantly aggravated airway inflammation injury in asthmatic rats. EGCG can reduce lung injury and airway remodeling in PM2.5-exposed asthmatic rats and has lung protective effects. The mechanism may be related to regulation of the HMGB1/RAGE signaling pathway. Our results may provide new ideas and methods for the prevention and treatment of PM2.5-induced asthma.

Rice Sucrose Partitioning Mediated by a Putative Pectin Methyltransferase and Homogalacturonan Methylesterification.

Homogalacturonan (HG) is the main component of pectins. HG methylesterification has recently emerged as a key determinant controlling cell attachment, organ formation, and phyllotaxy. However, whether and how HG methylesterification affects intercellular metabolite transport has rarely been reported. Here, we identified and characterized knockout mutants of the rice (Oryza sativa) OsQUA2 gene encoding a putative pectin methyltransferase. Osqua2 mutants exhibit a remarkable decrease in the degree of methylesterification of HG in the culm-sieve element cell wall and a markedly reduced grain yield. The culm of Osqua2 mutant plants contains excessive sucrose (Suc), and a 13CO2 feeding experiment showed that the Suc overaccumulation in the culm was caused by blocked Suc translocation. These and other findings demonstrate that OsQUA2 is essential for maintaining a high degree of methylesterification of HG in the rice culm-sieve element cell wall, which may be critical for efficient Suc partitioning and grain filling. In addition, our results suggest that the apoplastic pathway is involved in long-distance Suc transport in rice. The identification and characterization of the OsQUA2 gene and its functionality revealed a previously unknown contribution of HG methylesterification and provided insight into how modification of the cell wall regulates intercellular transport in plants.

Sabiporide improves cardiovascular function and attenuates organ injury from severe sepsis.

BACKGROUND: The aim of the present study was to evaluate the efficacy of orally administered sabiporide, a selective Na(+)/H(+) exchanger inhibitor on whole body protection from severe sepsis in rats. METHODS: Series 1: Sepsis was induced by cecal ligation and puncture (CLP). Animals received treatment of vehicle or sabiporide (10 mg/kg, p.o.). The experiment was terminated 20 h after CLP. Series 2: At 20 h after CLP, the necrotic cecum was excised and the abdominal cavity was washed. The animals were then returned to their cages. The experiment was terminated 7 d after CLP. RESULTS: Series 1: Compared with vehicle treatment, administration of sabiporide prevented hemodynamic derangement and improved cardiac function as evidenced by improved arterial pressure, left ventricle systolic pressure, ±dp/dt max, ejection fraction and fractional shorting, attenuated left ventricle end-diastolic pressure elevation, and wall motion abnormality. Furthermore, administration of sabiporide attenuated intestinal mucosal hyperpermeability and reduced accumulation of abdominal ascites. In addition, treatment with sabiporide also reduced plasma levels of tumor necrosis factor-α, interleukin 6, interleukin 10, cardiac troponin, aspartate aminotransferase, alanine aminotransferase, urea, and lactate, and attenuated neutrophil infiltration in the liver and gut. Series 2: Administration of sabiporide improved the 7-day survival rate after CLP in rats (42% in vehicle group versus 75% in sabiporide group). CONCLUSIONS: Administration of sabiporide improved cardiovascular performance, lessened the inflammatory response, tissue hypoperfusion and multiorgan injury, and most importantly reduced mortality.

[Study on genetic diversity of Curcuma wenyujin from various habitats by SRAP].

OBJECTIVE: The DNA fingerprints of Curcuma wenyujin from various habitats were generated by using SRAP markers to find the feasibility in analyzing their relationship. METHODS: The DNA polymorphism of Curcuma wenyujin from various habitats were detected by SRAP molecular markers. RESULTS: We had screened five pairs of primer combinations, and built the DNA fingerprints of Curcuma wenyujin from various habitats. The phylogenetic clustering results revealed that the genetic difference in Curcuma wenyujin from various habitats were little. CONCLUSION: SRAP markers may offer some evidence for protecting and exploiting of Curcuma wenyuji.

Proapoptotic effect of curcumin on human neutrophils: activation of the p38 mitogen-activated protein kinase pathway.

OBJECTIVE: Despite advances in the management of sepsis and acute respiratory distress syndrome, the mortality rate remains high. Delayed apoptosis of neutrophils is associated with multiple organ failure under those conditions. Thus, development of nontoxic neutrophil apoptosis regulating molecules may provide a novel therapeutic strategy. Curcumin is a promising dietary supplement for cancer prevention. However, the effect of curcumin on human neutrophil apoptosis remains unknown. We therefore hypothesized that curcumin would produce a proapoptotic effect on neutrophils. DESIGN: Prospective, controlled, and randomized in vitro study. SETTING: Research institute laboratory. SUBJECTS: Human peripheral neutrophils obtained from normal subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the presence or absence of curcumin, both spontaneous neutrophil apoptosis and apoptosis of neutrophils following transmigration across a human lung endothelium-epithelium bilayer were studied by morphology and terminal dUTP nucleotide end labeling analyses, respectively. Myeloperoxidase activity and migration assays were performed to determine the impact of curcumin on neutrophil function. To elucidate the potential mechanism, the p38 mitogen-activated protein kinase pathway and caspase-3 activity were examined by Western blotting and enzymatic analyses. The data demonstrate that curcumin increased constitutive neutrophil apoptosis and abrogated the transbilayer migration-induced delay in neutrophil apoptosis. Neutrophil activation was reduced by curcumin treatment as evidenced by a decrease in migration and myeloperoxidase release. A marked increase in p38 phosphorylation and caspase-3 activity was observed following curcumin exposure. In addition, inhibition of p38 mitogen-activated protein kinase with SB203580 suppressed apoptosis and caspase-3 activation induced by curcumin. Thus, activation of p38 mitogen-activated protein kinase or an increase in caspase-3 activity appears to contribute to the proapoptotic effect of human neutrophil apoptosis by curcumin. CONCLUSION: The characteristics of curcumin, including its proapoptotic effect and antidegranulation effect, make it a potential candidate for the therapy of neutrophil-induced lung injury and sepsis.