Do Plant Cyclotides Have Potential As Immunosuppressant Peptides?

Cyclotides are an abundant and diverse group of ribosomally synthesized plant peptides containing a cyclic cystine-knotted structure that confers them with remarkable stability. They are explored for their distribution in plants, although little is known about the individual peptide content of a single species. Therefore, we chemically analyzed the crude extract of the coffee-family plant Oldenlandia affinis using a rapid peptidomics workflow utilizing nano-LC-MS, peptide reconstruct with database identification, and MS/MS automated sequence analysis to determine its cyclotide content. Biologically, cyclotides are mainly explored for applications in agriculture and drug design; here we report their growth-inhibiting effects on primary cells of the human immune system using biological and immunological end points in cell-based test systems. LC-MS quantification of the active O. affinis plant extract triggered the characterization of the antiproliferative activity of kalata B1, one of the most abundant cyclotides in this extract, on primary activated human lymphocytes. The effect has a defined concentration range and was not due to cytotoxicity, thus opening a new avenue to utilize native and synthetically optimized plant cyclotides for applications in immune-related disorders and as immunosuppressant peptides

Additional file 1: Table S1. of Outcomes from a three-arm randomized controlled trial of frequent immersion in thermoneutral water on cardiovascular risk factors

Mineral content of the therapeutic pools (mg/L). (PDF 39 kb

Additional file 2: Table S2. of Outcomes from a three-arm randomized controlled trial of frequent immersion in thermoneutral water on cardiovascular risk factors

Antihypertensive medication (intention-to-treat population, N = 59). (PDF 52 kb

New Cruciform Structures: Toward Coordination Induced Single Molecule Switches

New cruciform structures 1−4 were synthesized to investigate a new single molecule switching mechanism arising from the interplay between the molecule and the electrode surface. These molecular cruxes consist of two rod-type substructures, namely an oligophenylenevinylene and an oligophenyleneethynyl. While the oligophenylenevinylene rods are functionalized with acetyl protected sulfur anchor groups, the oligophenyleneethynyl rods provide terminal pyridine units. The hypothesized switching mechanism should arise from the electrochemical potential dependent coordination of the pyridine unit to the electrode surface. The assembly of the oligophenylenevinylene substructure was based on a Wittig reaction whereas its perpendicular oligophenyleneethynyl rod was assembled by Sonogashira−Hagihara coupling reactions. Preliminary transport investigations with molecular cruciforms 2 and 4 in a mechanical controllable break junction in a liquid environment displayed the trapping of single molecules between two gold electrodes via the terminally sulfur functionalized oligophenylenevinylene rod

Electrical Conductance of Molecular Junctions by a Robust Statistical Analysis

We propose an objective and robust method to extract the electrical conductance of single molecules connected to metal electrodes from a set of measured conductance data. Our method roots in the physics of tunneling and is tested on octanedithiol using mechanically controllable break junctions. The single molecule conductance values can be deduced without the need for data selection

Additional file 1: of The impact of immunosuppression on postoperative graft function after graft-unrelated surgery: a retrospective controlled cohort study

Whole strategy of creation of control group, searched encryptions and definitions. (DOCX 42 kb

Bowel health, defecation patterns and nutrient intake following adoption of a vegan diet: a randomized-controlled trial

The beneficial effects of a plant-based diet on gut microbiota diversity are well documented, however, its impact on clinical bowel health and defecation patterns are less well understood. Vegetarian diets have been associated with a higher bowel movement (BM) frequency as well as softer stools in cross-sectional studies. The effects of the de-novo adoption of a vegan diet on bowel health, however, have never been investigated in a randomized-controlled trial. The present study examined bowel health and defecation patterns in relation to diet and nutrient intake in a young and healthy sample of n = 65 physically-active German university students who were randomly assigned to either a vegan or a meat-rich diet for eight weeks. Bowel health assessment included the Bristol Stool Form Scale (BSFS), the Gastrointestinal Quality of Life Index (GIQLI) and the Cleveland Clinic Fecal Incontinence Score (CCFIS). Nutrient intake was assessed using weighed food diaries. The study was prospectively registered at the German Clinical Trial Register (DRKS00031541). Weekly BM frequency slightly increased in vegans, whereas it remained unaltered in participants assigned to a meat-rich diet. Fiber intake increased significantly in vegans (34.89 (18.46) g/d) whereas it decreased in those assigned to the meat-rich group (22.79 (12.5) g/d). No significant intergroup differences in BSFS and CCFIS patterns were observed. Adoption of a vegan diet neither resulted in a transient increase in abdominal discomfort nor in a decreased gastrointestinal quality of life, which was comparable across the diet groups. The short-term de-novo adoption of a vegan diet did not negatively affect markers of bowel health in this study.</p

Sesquiterpene Lactones from <i>Artemisia argyi</i>: Absolute Configuration and Immunosuppressant Activity

A library of extracts from plants used in Chinese Traditional Medicine was screened for inhibition of T lymphocyte proliferation. An ethyl acetate extract from aerial parts of Artemisia argyi showed promising activity and was submitted to HPLC-based activity profiling to track the active compounds. From the most active time window, three guaianolides (1, 2, and 5) and two seco-tanapartholides (3 and 4) were identified and, in a less active time window, five new sesquiterpene lactones (8–11, 17), along with six known sesquiterpene lactones and two known flavonoids. The absolute configurations of compounds 1, 2, 5–10, 13–15, 17, and 18 were established by comparison of experimental with calculated electronic circular dichroism (ECD) spectra. For seco-tanapartholides B (3) and A (4), ECD yielded ambiguous results, and their absolute configurations were determined by comparing experimental and calculated vibrational circular dichroism (VCD) spectra. Compounds 1–5 showed significant, noncytotoxic inhibition of T lymphocyte proliferation, with IC50 values between 1.0 and 3.7 μM

Presentation_1_Longitudinal dynamics of gut bacteriome and mycobiome interactions pre- and post-visceral surgery in Crohn’s disease.zip

IntroductionAlterations of the gut microbiome are involved in the pathogenesis of Crohn’s disease (CD). The role of fungi in this context is unclear. This study aimed to determine postoperative changes in the bacterial and fungal gut communities of CD patients undergoing intestinal resection, and to evaluate interactions between the bacteriome and mycobiome and their impact on the patients’ outcome.MethodsWe report a subgroup analysis of a prospective cohort study, focusing on 10 CD patients whose fecal samples were collected for bacterial 16S rRNA and fungal ITS2 genes next-generation sequencing the day before surgery and on the 5th or 6th postoperative day.ResultsNo significant differences in bacterial and fungal diversity were observed between preoperative and postoperative stool samples. By in-depth analysis, significant postoperative abundance changes of bacteria and fungi and 17 interkingdom correlations were detected. Network analysis identified 13 microbial clusters in the perioperative gut communities, revealing symbiotic and competitive interactions. Relevant factors were gender, age, BMI, lifestyle habits (smoking, alcohol consumption) and surgical technique. Postoperative abundance changes and identified clusters were associated with clinical outcomes (length of hospital stay, complications) and levels of inflammatory markers.ConclusionsOur findings highlight the importance of dissecting the interactions of gut bacterial and fungal communities in CD patients and their potential influence on postoperative and disease outcomes.</p