Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules of innate immunity, which are firstly found in mammalians. Recently, several cathelicidins have also been found from chickens and fishes. No cathelicidins from other non-mammalian vertebrates have been reported. In this work, a cathelicidin-like antimicrobial peptide named cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and its cDNA sequence was cloned from the cDNA library, which confirm the presence of cathelicidin in reptiles. As other cathelicidins, the precursor of cathelicidin-BF has cathelin-like domain at the N terminus and carry the mature cathelicidin-BF at the C terminus, but it has an atypical acidic fragment insertion between the cathelin-like domain and the C-terminus. The acidic fragment is similar to acidic domains of amphibian antimicrobial precursors. Phylogenetic analysis revealed that the snake cathelicidin had the nearest evolution relationship with platypus cathelicidin. The secondary structure of cathelicidin-BF investigated by CD and NMR spectroscopy in the presence of the helicogenic solvent TFE is an amphipathic α-helical conformation as many other cathelicidins. The antimicrobial activities of cathelicidin BF against forty strains of microorganisms were tested. Cathelicidin-BF efficiently killed bacteria and some fungal species including clinically isolated drug-resistance microorganisms. It was especially active against Gram-negative bacteria. Furthermore, it could exert antimicrobial activity against some saprophytic fungus. No hemolytic and cytotoxic activity was observed at the dose of up to 400 µg/ml. Cathelicidin-BF could exist stably in the mice plasma for at least 2.5 hours. Discovery of snake cathelicidin with atypical structural and functional characterization offers new insights on the evolution of cathelicidins. Potent, broad spectrum, salt-independent antimicrobial activities make cathelicidin-BF an excellent candidate for clinical or agricultural antibiotics.

¹H nuclear magnetic resonance (NMR)‐based metabonomics was used to characterize metabolic profiles of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We found compared to healthy humans, LC and HCC sera had higher levels of acetate, N‐acetylglycoproteins, pyruvate, glutamine, α‐ketoglutarate, glycerol, tyrosine, 1‐methylhistidine and phenylalanine, together with lower levels of low‐density lipoprotein, isoleucine, valine, acetoacetate, creatine, choline and unsaturated lipids. Scores plot of pattern recognition analysis were capable of distinguishing LC and HCC patients from healthy humans. These results indicate that serum NMR spectra combined with pattern recognition analysis techniques offer an efficient, convenient way of depicting tumor biochemistry, which may be of great benefit to early diagnosis of human malignant diseases using single blood samples. (Cancer Sci 2009; 100: 782–785)

Rabbits are one of the few mammalian species that appear to be resistant to transmissible spongiform encephalopathies due to the structural characteristics of the rabbit prion protein (RaPrP^C) itself. Here, we determined the solution structures of the recombinant protein RaPrP^C-(91–228) and its S173N variant and detected the backbone dynamics of their structured C-terminal domains-(121–228). In contrast to many other mammalian PrP^Cs, loop 165–172, which connects β-sheet-2 and α-helix-2, is well-defined in RaPrP^C. For the first time, order parameters S² are obtained for residues in this loop region, indicating that loop 165–172 of RaPrP^C is highly ordered. Compared with the wild-type RaPrP^C, less hydrogen bonds form in the S173N variant. The NMR dynamics analysis reveals a distinct increase in the structural flexibility of loop 165–172 and helix-3 after the S173N substitution, implying that the S173N substitution disturbs the long range interaction of loop 165–172 with helix-3, which further leads to a marked decrease in the global conformational stability. Significantly, RaPrP^C possesses a unique charge distribution, carrying a continuous area of positive charges on the surface, which is distinguished from other PrP^Cs. The S173N substitution causes visible changes of the charge distribution around the recognition sites for the hypothetical protein X. Our results suggest that the ordered loop 165–172 and its interaction with helix-3, together with the unique distribution of surface electrostatic potential, significantly contribute to the unique structural characteristics of RaPrP^C.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Colorectal adenomatous polyps are at high risk for the development of CRC. In this report, we described the metabolic changes in the sera from patients with colorectal polyps and CRC by using the NMR-based metabolomics. 110 serum samples were collected from patients and healthy controls, including 40 CRC patients, 32 colorectal polyp patients, and 38 healthy controls. The metabolic profiles and differential metabolites of sera were analyzed by multivariate statistical analysis (MSA), including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. A total of 23 differential metabolites were identified from MSA. According to the pathway analysis and multivariate ROC curve-based exploratory analysis by using the relative concentrations of differential metabolites, we found abnormal metabolic pathways and potential biomarkers involved with the colorectal polyp and CRC. The results showed that the pyruvate metabolism and glycerolipid metabolism were activated in colorectal polyps. And the glycolysis and glycine, serine, and threonine metabolism were activated in CRC. The changed metabolism may promote cellular proliferation. In addition, we found that the rates of acetate/glycerol and lactate/citrate could be the potential biomarkers in colorectal polyp and CRC, respectively. The application of ¹H-NMR metabolomics analysis in serum has interesting potential as a new detection and diagnostic tool for early diagnosis of CRC.

Bladder cancer (BC) is one of the most common cancers and has a high mortality rate. However, both metabolite variations and metabolic pathways related to the pathogenic process of BC remain to be addressed, such results might contribute to early detection of the disease. 1H nuclear magnetic resonance (NMR)-based metabolomics was applied to identify differences of serum metabolic profiles among BC, calculi patients and healthy subjects. Serum metabolic profiles of BC patients are distinctly different from those of calculi and healthy subjects. Compared with those from healthy subjects, serum samples from BC patients show decreased levels of isoleucine/leucine, tyrosine, lactate, glycine, citrate, as well as increased levels of lipids and glucose. The results reveal disturbed metabolic pathways of aromatic amino acids, glycolysis and citrate cycle, as well as lipogenesis metabolism in BC patients. Our work will be of potential benefit to understanding the pathogenic process of BC and will offer valuable information for noninvasive diagnosis of the disease.