Borneol and Luteolin from Chrysanthemum morifolium Regulate Ubiquitin Signal Degradation

Targeting the two degradation systems, ubiquitin proteasome pathway and ubiquitin signal autophagy lysosome system, plays an important function in cancer prevention. Borneol is called an “upper guiding drug”. Luteolin has demonstrated anticancer activity. The fact that borneol regulates luteolin can be sufficient to serve as an alternative strategy. Borneol activates luteolin to inhibit E1 and 20S activity (IC₅₀ = 118.8 ± 15.7 μM) and perturb the 26S proteasome structure <i>in vitro</i>. Borneol regulates luteolin to inhibit 26S activity (IC₅₀ = 157 ± 19 μM), induces apoptosis (LC₅₀ = 134 ± 4 μM), and causes pre-G1 and G0/G1 arrest in HepG2 cells. Borneol regulates luteolin to induce ubiquitin signal autophagic degradation, resulting in induction of E1, reduction of USP47, and accumulation of p62 in HepG2 reporter cells. Interestingly, luteolin decreased Ub conjugates, while borneol increased the accumulation of Ub conjugates in HepG2 reporter cells. E1, p62, and ubiquitin levels were downregulated in borneol-treated HepG2 reporter cells at 24 h. These observations suggest a potential autophagic inhibitor of borneol that may guide luteolin in the ubiquitin proteasome pathway and the ubiquitin signal autophagic degradation

<i>Clostridium difficile</i> Infections in Medical Intensive Care Units of a Medical Center in Southern Taiwan: Variable Seasonality and Disease Severity

<div><p>Critical patients are susceptible to <i>Clostridium difficile</i> infections (CDIs), which cause significant morbidity and mortality in the hospital. In Taiwan, the epidemiology of CDI in intensive care units (ICUs) is not well understood. This study was aimed to describe the incidence and the characteristics of CDI in the ICUs of a medical center in southern Taiwan. Adult patients with diarrhea but without colostomy/colectomy or laxative use were enrolled. Stool samples were collected with or without 5 ml alcohol and were plated on cycloserine-cefoxitin-fructose agar. <i>C</i>. <i>difficile</i> identification was confirmed by polymerase chain reaction. There were 1,551 patients admitted to ICUs, 1,488 screened, and 145 with diarrhea. A total of 75 patients were excluded due either to laxative use, a lack of stool samples, or refusal. Overall, 70 patients were included, and 14 (20%) were diagnosed with CDI, with an incidence of 8.8 cases per 10,000 patient-days. The incidence of CDI was found to be highest in March 2013 and lowest in the last quarter of 2013. The cases were categorized as the following: 5 severe, complicated, 5 severe, and 4 mild or moderate diseases. Among the 14 cases of CDI, the median patient age was 74 (range: 47–94) years, and the median time from admission to diarrhea onset was 16.5 (4–53) days. Eight cases received antimicrobial treatment (primarily metronidazole), and the time to diarrheal resolution was 11.5 days. Though 6 cases were left untreated, no patients died of CDI. The in-hospital mortality of CDI cases was 50%, similar to that of patients without CDI (46.4%; <i>P</i> = 1.0). We concluded that the overall incidence of CDI in our medical ICUs was low and there were variable seasonal incidences and disease severities of CDI.</p></div

The incidences of <i>Clostridium difficile</i> infection (CDI) in different clinical settings.

<p>The incidences of CDI in a medical center (NCKUH) and a regional hospital (TH) between March 2013 and March 2014. CDI was diagnosed by the presence of toxigenic <i>C</i>. <i>difficile</i> isolates (Culture+) or <i>C</i>. <i>difficile</i> toxin (Toxin+) in stools. mICUs = medical intensive care units.</p

Characteristics of the patients with or without <i>Clostridium difficile</i> infection (CDI) in intensive care units (ICUs).

<p>Characteristics of the patients with or without <i>Clostridium difficile</i> infection (CDI) in intensive care units (ICUs).</p

Patient flowchart of <i>Clostridium difficile</i> infection in ICUs.

<p>CCFA = cycloserine-cefoxitin fructose agar; CDSA <i>= Clostridium difficile</i> selective agar; PCR = polymerase chain reaction.</p

MOESM1 of Comparative genomic analysis of Clostridium difficile ribotype 027 strains including the newly sequenced strain NCKUH-21 isolated from a patient in Taiwan

Additional file 1. Materials and methods

Clinical Implications of Species Identification in Monomicrobial <i>Aeromonas</i> Bacteremia

<div><p>Background</p><p>Advances in <i>Aeromonas</i> taxonomy have led to the reclassification of aeromonads. Hereon, we aimed to re-evaluate the characteristics of <i>Aeromonas</i> bacteremia, including those of a novel species, <i>Aeromonas dhakensis</i>.</p><p>Methodology/Principal Findings</p><p>A retrospective study of monomicrobial <i>Aeromonas</i> bacteremia at a medical center in southern Taiwan from 2004–2011 was conducted. Species identification was based on <i>rpoB</i> sequencing. Of bacteremia of 153 eligible patients, <i>A. veronii</i> (50 isolates, 32.7%), <i>A. dhakensis</i> (48, 31.4%), <i>A. caviae</i> (43, 28.1%), and <i>A. hydrophila</i> (10, 6.5%) were the principal causative species. <i>A. dhakensis</i> and <i>A. veronii</i> bacteremia were mainly community-acquired and presented as primary bacteremia, spontaneous bacterial peritonitis, or skin and soft-tissue infection, whereas <i>A. caviae</i> was associated with hospital-onset bacteremia. The distribution of the AmpC β-lactamase and metallo-β-lactamase genes was species-specific: <i>bla</i>_AQU-1, <i>bla</i>_MOX, or <i>bla</i>_CepH was present in <i>A. dhakensis</i>, <i>A. caviae</i>, or <i>A. hydrophila</i>, respectively, and <i>bla</i>_CphA was present in <i>A. veronii</i>, <i>A. dhakensis</i>, and <i>A. hydrophila</i>. The cefotaxime resistance rates of the <i>A. caviae</i>, <i>A. dhakensis</i>, and <i>A. hydrophila</i> isolates were higher than that of <i>A. veronii</i> (39.5%%, 25.0%, and 30% <i>vs.</i> 2%, respectively). <i>A. dhakensis</i> bacteremia was linked to the highest 14-day sepsis-related mortality rate, followed by <i>A. hydrophila</i>, <i>A. veronii</i>, and <i>A. caviae</i> bacteremia (25.5%, 22.2%, 14.0%, and 4.7%, respectively; <i>P</i> = 0.048). Multivariate analysis revealed that <i>A. dhakensis</i> bacteremia, active malignancies, and a Pitt bacteremia score ≥ 4 was an independent mortality risk factor.</p><p>Conclusions/Significance</p><p>Characteristics of <i>Aeromonas</i> bacteremia vary between species. <i>A. dhakensis</i> prevalence and its associated poor outcomes suggest it an important human pathogen.</p></div

Kaplan-Meier survival curves for 148 patients with monomicrobial bacteremia caused by <i>Aeromonas veronii</i>, <i>A</i>. <i>dhakensis</i>, <i>A</i>. <i>caviae</i>, and <i>A</i>. <i>hydrophila</i> (Log-rank test, <i>P</i> = 0.02).

<p>Kaplan-Meier survival curves for 148 patients with monomicrobial bacteremia caused by <i>Aeromonas veronii</i>, <i>A</i>. <i>dhakensis</i>, <i>A</i>. <i>caviae</i>, and <i>A</i>. <i>hydrophila</i> (Log-rank test, <i>P</i> = 0.02).</p

Predominance of <i>Clostridium difficile</i> Ribotypes 017 and 078 among Toxigenic Clinical Isolates in Southern Taiwan

<div><p>Ribotypes and toxin genotypes of clinical <i>C</i>. <i>difficile</i> isolates in Taiwan are rarely reported. A prospective surveillance study from January 2011 to January 2013 was conducted at the medical wards of a district hospital in southern Taiwan. Of the first toxigenic isolates from 120 patients, 68 (56.7%) of 120 isolates possessed both <i>tcdA</i> and <i>tcdB</i>. Of 52 (43.3%) with <i>tcdB</i> and truncated <i>tcdA</i> (<i>tcdA</i>-/<i>tcdB</i>+), all were ribotype 017 and none had binary toxin or <i>tcdC</i> deletion. Eighteen (15%) toxigenic isolates harbored binary toxins (<i>cdtA</i> and <i>cdtB</i>) and all had <i>tcdC</i> deletion, including Δ39 (C184T) deletion (14 isolates), Δ18 in-frame deletion (3 isolates), and Δ18 (Δ117A) deletion (1 isolate). Eleven of 14 isolates with Δ39 (C184T) deletion belonged to the ribotype 078 family, including ribotype 127 (6 isolates), ribotype 126 (4 isolates), and ribotype 078 (1 isolate). Among 8 patients with consecutive <i>C</i>. <i>difficile</i> isolates, these isolates from 6 (75%) patients were identical, irrespective of the presence or absence of diarrhea, suggestive of persistent fecal carriage or colonization. In conclusion in southern Taiwan, ribotype 017 isolates with a <i>tcdA</i>-/<i>tcdB</i>+ genotype were not uncommon and of <i>C</i>. <i>difficile</i> isolates with binary toxin, the ribotype 078 family was predominant.</p></div

The toxin gene content and ribotype of consecutive toxigenic <i>Clostridium difficile</i> isolates.

<p>The toxin gene content and ribotype of consecutive toxigenic <i>Clostridium difficile</i> isolates.</p