Effects of adiponectin on acute lung injury in cecal ligation and puncture-induced sepsis rats.

BACKGROUND: The purpose of this study was to elucidate the possible beneficial effects of adiponectin (APN) on acute lung injury in a rat model of sepsis. METHODS: We subjected male Sprague-Dawley rats to cecal ligation and puncture (CLP) to establish sepsis models. We randomly animals divided into four groups: control (C), model (CLP), preemptive APN administration (APN plus CLP), and delayed APN administration (CLP plus APN). We killed the animals 24 h after CLP and collected blood samples to determine PaO2 and PaCO2. Lung samples were taken for histologic assessment and measurement of myeloperoxidase activity. We measured neutrophil and macrophage count and cytokine production (tumor necrosis factor-α and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid. RESULTS: Histology findings and lung injury score analysis revealed acute lung injury in rats in the CLP group, whereas those in the APN-treated group had mild lung injury. The effects of sepsis on the increasing cell number in bronchoalveolar lavage fluid as well as the wet/dry weight ratio, neutrophil infiltration, and myeloperoxidase activity of lung tissue were significantly attenuated by APN administration. Adiponectin also significantly alleviated hypoxemia and hypercapnia resulting from the development of lung injury. In addition, in APN-treated rats, the levels of pulmonary inflammatory molecule (macrophage inflammatory protein-2) and cytokine (tumor necrosis factor-α) were down-regulated compared with the CLP group. CONCLUSIONS: Adiponectin administration ameliorates acute lung injury in a rat model of sepsis induced by CLP, no matter whether it is administrated before or after the onset of sepsis.

OGA activated glycopeptide-based nano-activator to activate PKM2 tetramerization for switching catabolic pathways and sensitizing chemotherapy resistance.

Tumor cells intensively engage in metabolic reprogramming for enhancing the availability of glycolytic metabolites and support cell proliferation. As the most important rate-limiting enzyme in aerobic glycolysis, activating the pyruvate kinase muscle isoform 2 (PKM2) from dimers to tetramers has become a key tumor chemotherapy method to control glucose metabolism. Herein, we developed a glycopeptide-based PKM2 nano-activator, which could induce the tetramerization of PKM2 based on serine bonding to Domain C of PKM2. The bound and trapped PKM2 tetramers significantly hindered glycolytic intermediates, prevented the nucleus translocation of dimeric PKM2, and ultimately inhibited the proliferation, chemoresistance and metastasis of tumor. The glycopeptide assembled into nanoparticles under aqueous conditions and in the circulation, which in situ transformed into PKM2 nano-activator with nanofibrillar structure after specifically activated by O-GlcNAcase recognition upregulated in a wide range of human tumors. Moreover, the glycopeptide-based PKM2 nano-activator successfully accumulated at the tumor sites and boosted the chemo-drug sensitivity against prostate and breast cancers. Attributed to these intriguing results, the newly developed glycopeptide-based PKM2 nano-activator can be envisioned a promising candidate for the treatment of tumors by switching catabolic pathways.

[Polyhydroxyalkanoates microbiological synthesis from food wastes].

To reduce the production cost of polyhydroxyalkanoates (PHAs), the process feasibility and physicochemical properties of PHAs synthesized by Alcaligenes latus, Staphylococcus epidermidis and activated sludge from malt waste, soy waste, confectionary waste, ice cream waste, milk waste, sesame oil and vinegar waste were analyzed. Results showed that through two-stage fed-batch fermentation, the maximum yield of PHAs accumulated by the three kinds of microorganisms from malt waste was 70.1%, 16.0% and 43.3%, separately. A. latus adapted itself to the food wastes in PHAs synthesis and new cell growth quickly. A. latus had higher PHAs yield and productivity under nitrogen limited condition. Micro-aerobically, S. epidermidis separated from sesame oil could produce polyhydroxybutyrate (PHB) with molecular weight of over 1 x 10(6). From soy waste, activated sludge accumulated polyhydroxybutyrate-co-hydroxyvaluate (PHBV) copolymer which had hydroxyvaleryl content (HV%) of 21%. Most food wastes are suitable for synthesizing PHAs with different physicochemical properties. The composition and properties of PHAs are influenced by the character of microorganism, the selection of substrates and optimization of ferment conditions.