Non hemolytic short peptidomimetics as a new class of potent and broad-spectrum antimicrobial agents

Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics.     

Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis

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Highlights? Two-way modulations of adipose VEGF were generated with aP2-Cre transgene ? Adipose VEGF KO reduces vasculature, increases hypoxia and inflammation in fat ? Adipose VEGF KO accelerates the development of metabolic disease in high-fat diet ? Induced adipose VEGF has opposite effect on fat and restores metabolic homeostasis     

Molecular cloning of an alanine aminotransferase from NAD-malic enzyme type C4 plant Panicum miliaceum

We have determined the nucleotide sequence of a cDNA encoding AlaAT-2, which is believed to function in the C4-pathway of Panicum miliaceum. An open reading frame (1446 bp) encodes a protein of 482 amino acid residues. The deduced amino acid sequence of AlaAT-2 shows 44.2 and 44.8% homology with the amino acid sequences of AlaATs from rat and human livers, respectively. Northern blot analysis showed that the gene encoding AlaAT-2 in mesophyll and bundle sheath cells was the same and transcribed similarly in the cells. The level of translatable mRNA for AlaAT-2 increased dramatically during greening.     

Costimulatory Effect of Fas in Mouse T Lymphocytes

To induce proper immune responses, T lymphocytes require two types of stimuli, antigen-specific and costimulatory signals. Among costimulatory molecules, CD28-engagement promotes the survival and proliferation of both naive and memory T cells. In addition, it is now believed that Fas may play a role in T cell activation in the human system. It is, however, controversial whether Fas can act as a costimulatory signal in the murine system. Thus, we investigated fundamental differences in the capacity to induce proliferation of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferation was observed only with a full mitogenic dose of anti-CD3 antibodies, whereas CD28 engagement was able to enhance T cell proliferation in the presence of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T cells showed faster response in the upregulation of CD25 and CD69 expression than CD28-engaged ones. Here, we report that Fas might play a role in mature T cell activation in the mouse system through a different mechanism from that in CD28 costimulation.     

Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis

Molecular and Cellular Biochemistry - Electron transfer occurs through heme-Fe across the cytochrome c protein. The current models of long range electron transfer pathways in proteins include...     

Visfatin induces sickness responses in the brain

Background/Objective

Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity.

Methodology

Rats were intracerebroventricularly (ICV) injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC) and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX) and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated.

Principal Findings

Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity.

Conclusions

Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain.     

Glucosylation of the flavonoid, astragalin by Leuconostoc mesenteroides B-512FMCM dextransucrase acceptor reactions and characterization of the products

Astragalin (kaempferol-3-O-β-d-glucopyranoside, Ast) glucosides were synthesized by the acceptor reaction of a dextransucrase produced by Leuconostoc mesenteroides B-512FMCM with astragalin and sucrose. Each glucoside was purified and their structures were assigned as kaempferol-3-O-β-d-glucopyranosyl-(1 → 3)-O-α-d-glucopyranoside (or kaempferol-3-O-β-d-nigeroside, Ast-G1′) and kaempferol-3-O-β-d-glucopyranosyl-(1 → 6)-O-α-d-glucopyranoside (or kaempferol-3-O-β-d-isomaltoside, Ast-G1) for one glucose transferred, and kaempferol-3-O-β-d-isomaltooligosacharide (Ast-IMO or Ast-Gn; n = 2-8). The astragalin glucosides exhibited 8.3-60.6% higher inhibitory effects on matrix metalloproteinase-1 expression, 18.8-20.3% increased antioxidant effects, and 3.8-18.8% increased inhibition activity of melanin synthesis compared to control (without the addition of compound), depending on the number of glucosyl residues linked to astragalin. These novel compounds could be used to further expand the industrial applications of astragalin glucosides, in particular in the cosmetics industry.     

Glycation of lysozyme with galactose,galactooligosaccharides and potato galactan through the Maillard reaction and optimization of the production of prebiotic glycoproteins

The production of glycated lysozyme (LZM), with galactose, galactooligosaccharides (GOSs) and potato galactan through the Maillard reaction, was investigated. The percent blocked lysine, estimated from the furosine content, reached a maximum value of 11.2% for LZM:galactan conjugates after 1 day incubation at a a_w of 0.65. A maximum percent blocked lysine of 7.0 and 13.5% were obtained for LZM:galactose/GOS conjugates at a lower a_w of 0.45 after 3 and 7 days, respectively. However, the low percent blocked lysine and the high protein aggregation index of LZM:galactose/GOS conjugates at a_w 0.79 and 0.65 revealed the prevalence of the degradation of the Amadori compounds and the protein cross-linking. Mass spectrometry of LZM conjugates revealed the formation of different glycoforms. Glycated LZMs containing up to seven galactose moieties were formed; while only mono- and diglycated LZMs with GOSs were detected. 2–3 mol of galactan were conjugated to 1 mol of LZM. Response surface methodology, based on a 5-level and 3-factor central composite design, revealed that molar ratio and temperature were the most significant variables for the glycation of LZM with GOSs. The optimal conditions leading to a high percent blocked lysine (16.11%) with a low protein aggregation index (0.11) were identified: temperature of 49.5 °C, LZM:GOS molar ratio of 1:9 and a_w of 0.65. To the best of our knowledge, this is the first study on the optimization of LZM glycation with GOSs.