Xinnaokang improves cecal microbiota and lipid metabolism to target atherosclerosis

This study aims to explore the potential mechanisms of Xinnaokang in atherosclerosis treatment. Firstly, the active components of Xinnaokang were analysed by HPLC, which contains ginsenoside Rg1, puerarin, tanshinone, notoginsenoside R1, ammonium glycyrrhizate and glycyrrhizin. Network pharmacology analysis showed there were 145 common targets of Xinnaokang, including the chemical stress, lipid metabolite, lipopolysaccharide, molecules of bacterial origin, nuclear receptor and fluid shear stress pathways. Then, the animal experiment showed that Xinnaokang reduced the body weight and blood lipid levels of atherosclerotic mice. Vascular plaque formation was increased in atherosclerotic mice, which was markedly reversed by Xinnaokang. In addition, Xinnaokang reduced CAV-1 expression and increased ABCA1, SREBP-1 and LXR expressions in the vasculature. Xinnaokang promoted SREBP-2 and LDLR expressions in the liver but decreased IDOL and PCSK9 expressions, indicating that Xinnaokang regulated lipid transport-related protein expression. Cecal microbiota diversity was reduced in atherosclerotic mice but increased after Xinnaokang treatment. Xinnaokang treatment also improved gut microbiota communities by enriching Actinobacteria, Bifidobacteriales and Bifidobacteriaceae abundances. Metabolic profile showed that Xinnaokang significantly reduced homogentisate, phenylacetylglycine, alanine and methionine expressions in the liver of atherosclerotic mice. Xinnaokang effectively alleviated atherosclerosis, and this effect might be linked with the altered features of the liver metabolite profiles and cecal microbiota.     

Crystal structure of a novel mid-gut procarboxypeptidase from the cotton pest Helicoverpa armigera.

The cotton bollworm Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) is one of the most serious insect pests in Australia, India and China. The larva causes substantial economical losses to legume, fibre, cereal oilseed and vegetable crops. This pest has proven to be difficult to control by conventional means, mainly due to the development of pesticide resistance. We present here the 2.5 A crystal structure from the novel procarboxypeptidase (PCPAHa) found in the gut extracts from H. armigera larvae, the first one reported for an insect. This metalloprotease is synthesized as a zymogen of 46.6 kDa which, upon in vitro activation with Lys-C endoproteinase, yields a pro-segment of 91 residues and an active carboxypeptidase moiety of 318 residues. Both regions show a three-dimensional structure quite similar to the corresponding structures in mammalian digestive carboxypeptidases, the most relevant structural differences being located in the loops between conserved secondary structure elements, including the primary activation site. This activation site contains the motif (Ala)(5)Lys at the C terminus of the helix connecting the pro- and the carboxypeptidase domains. A remarkable feature of PCPAHa is the occurrence of the same (Ala)(6)Lys near the C terminus of the active enzyme. The presence of Ser255 in PCPAHa instead of Ile and Asp found in the pancreatic A and B forms, respectively, enlarges the S1' specificity pocket and influences the substrate preferences of the enzyme. The C-terminal tail of the leech carboxypeptidase inhibitor has been modelled into the PCPAHa active site to explore the substrate preferences and the enzymatic mechanism of this enzyme.     

Chewing lice from high‐altitude and migrating birds in Yunnan,China, with descriptions of two new species of Guimaraesiella

In total, 366 birds representing 55 species in 24 families and eight orders, were examined for chewing lice (Phthiraptera: Amblycera, Ischnocera) in two high‐altitude localities in Yunnan Province, China. In Ailaoshan, almost all of the birds examined were resident passeriforms, of which 36% were parasitized by chewing lice. In Jinshanyakou, most birds were on migration, and included both passerine and non‐passerine birds. Of the passerine birds caught in Jinshanyakou, only one bird (0.7%) was parasitized by chewing lice. The prevalence of Myrsidea and Brueelia‐complex lice on birds caught in Ailaoshan was higher than in previous reports. Of the chewing lice identifiable to species level, three represent new records for China: Actornithophilus hoplopteri (Mjöberg, 1910), Maculinirmus ljosalfar Gustafsson & Bush, 2017 and Quadraceps sinensis Timmermann, 1954. In total, 17 new host records are included, of which we describe two as new species in the Brueelia‐complex: Guimaraesiella (Cicchinella) ailaoshanensis sp. nov. ex Schoeniparus dubius dubius (Hume, 1874) and G. (C.) montisodalis sp. nov. ex Fulvetta manipurensis tonkinensis Delacour & Jabouille, 1930. This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:9FC3D8EE‐2CED‐4DBE‐A1DB‐471B71260D27 .     

Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms

We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.     

Comparison of whole-cell protein electrophoretic profiles of Haemophilus influenzae: implementation of a microcomputer mainframe linked system and description of a new similarity coefficient

A microcomputer mainframe linked system is described which allows video camera data capture and storage of one-dimensional whole-cell protein electrophoresis gel images, processing of normalized traces to produce a similarity matrix, and analysis of the matrix using the commercial cluster analysis program CLUSTAN. A new similarity coefficient is introduced which takes into account both band position and intensity. Forty-five strains of Haemophilus influenzae, including the eight biotypes and six serotypes, were analyzed using this system. Results demonstrated groupings which are consistent with known genetic relationships.     

Physical and enzymatic properties of a class III isozyme of human liver alcohol dehydrogenase: chi-ADH

chi-Alcohol dehydrogenase (chi-ADH), a class III isozyme characterized by its anodic electrophoretic mobility and lack of inhibition by 4-methylpyrazole, has been isolated from human liver and purified to homogeneity in a reducing medium. chi-ADH resembles other human liver ADH isozymes of classes I and II with respect to its molecular weight, dimeric structure, stoichiometry of zinc and NADH binding, and pH optima for the oxidation of alcohols. This homodimer exhibits subtle differences in its absorption spectrum and amino acid composition relative to those of other human isozymes but differs markedly from their specificity toward alcohols and aldehydes. chi-ADH oxidizes ethanol very poorly. The reaction is bimolecular, and an apparent Km cannot be discerned up to 2.3 M ethanol. The enzyme is inactive toward methanol, ethylene glycol, digitoxigenin, digoxigenin, and gitoxigenin , but alcohols with carbon chain lengths greater than four are oxidized rapidly with Km values decreasing with increasing carbon chain length. Taken jointly, the composition, structure, and enzymatic properties of the ADH isozymes purified and studied so far strongly imply that their metabolic roles, yet to be discovered, will give a new perspective to ethanol metabolism and pathology.     

A molecular dynamics study of a model built Pro-36-Gly mutant derived from the potato carboxypeptidase A inhibitor protein

A 120ps molecular dynamics (MD) trajectory was calculated and analyzed for a putative Pro-36-Gly mutant of the potato carboxypeptidase A (CPA) protein inhibitor (PCIm). The mutant protein's fold shows a large degree of stability, judged from its low alpha-carbon r.m.s. deviation from the X-ray structure of the wild type PCI (PCIw). The N-terminal tail of PCIm differs slightly less from the X-ray structure than it does in PCIw, while the mutant's C-terminal tail (the primary contact site with CPA) and residues 13-17 present deviations as they approach each other. Differences in fluctuation pattern exist between PCIm and PCIw in residues 2-4 (the N-terminal tail), 13-17, 22-23, 28-31 (the secondary contact site with CPA) and 37-38 (the C-terminal tail); the latter region is rigidified in PCIm. Results show that the MD method is able to sense local perturbative effects produced by amino acid substitutions in flexible regions of protein molecules. The simulation suggests that the conformation of the C-terminal tail is less favorable for interaction with the target protein in the mutant than it is in the wild type protein. The Pro-36-Gly mutant is predicted to be a less potent inhibitor.