Aims of the study
The ability of Yersinia enterocolitica strains to form biofilms and the capacity of different alkaloids to inhibit biofilm formation were investigated.
Methods and Results
The ...capacity to form biofilm on polystyrene of 31 Y. enterocolitica strains was evaluated. Biofilm and quorum sensing (QS) inhibition of 17 alkaloids were assayed; furthermore, minimum biofilm inhibitory concentration (MBIC) was determined. The capacity to form biofilms among the examined strains seemed to be a strain‐related feature. The best biofilm inhibitors at 100 µmol l−1 were oliverine (1), guatterine (3), liriodenine (4), oliveridine (5) and pachypodanthine (6), which showed biofilm inhibition higher than 87%. Pachypodanthine (6) was the most effective compound with MBIC value of 12·5 µmol l−1 at subinhibitory concentration and also was able to inhibit QS system and reduce yenR expression at this concentration.
Conclusion
This is the first study to demonstrate that oliverine, liriodenine, and pachypodanthine are able to inhibit biofilm formation of Y. enterocolitica without critically disturbing its growing capacity. At MBIC, pachypodanthine inhibited biofilm formation and QS.
Significance and Impact of the Study
The use of aporphinoid alkaloids as biofilms inhibitory agents might potentially be useful to treat biofilm‐associated infections in the future.
The capacity of different naphthoquinones to inhibit and eradicate
Yersinia enterocolitica
biofilm was investigated and possible mechanisms of action were evaluated. Inhibition of biofilm formation ...and cell viability, quorum sensing (QS) inhibition and oxidative stress generation of 23 naphthoquinones were assayed against
Yersinia enterocolitica
. The best anti-biofilm agents at 100 µmol l
−1
were compounds
3
,
11
and
13
, which showed biofilm inhibition higher than 75%. Compound
3
was the most effective against biofilm forming capacity of
Y. enterocolitica
WAP 314 with a minimum biofilm inhibitory concentration (MBIC) of 25 µmol l
−1
; while against
Y. enterocolitica
CLC001, the lowest MBIC was 6.1 µmol l
−1
for compound
11
. Acyl-homoserine lactones production was decreased with compound
13
. We showed that the oxidative stress influence biofilm growth, by means of ROS and RNI increment. All treatments increased ROS and RNI values in the biofilm of both strains; while in planktonic cells, the increase was lesser. Additionally,
Y. enterocolitica
WAP 314 biofilm treated with compounds
11
and
13
showed above 80% of SOD consumption. In
Y. enterocolitica
CLC001 biofilm all compounds induced above 90% of SOD consumption. The SOD activity was higher in biofilm than in planktonic cells. In conclusion, this is the first study to demonstrate that naphthoquinones are able to inhibit biofilm formation of
Y. enterocolitica
without critical disturbing its planktonic growth. Naphthoquinones as anti-biofilm agents might potentially be useful in the treatment of biofilm-associated infections in the future.
Graphic abstract
The optimal strategy for initial respiratory support in patients with respiratory failure associated with COVID-19 is unclear, and the initial strategy may affect outcomes.
Which initial respiratory ...support strategy is associated with improved outcomes in patients with COVID-19 with acute respiratory failure?
All patients with COVID-19 requiring respiratory support and admitted to a large health care network were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (NIRS; noninvasive positive pressure ventilation by facemask or high-flow nasal oxygen) with patients treated initially with invasive mechanical ventilation (IMV). The primary outcome was time to in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths of stay (ICU and hospital), and time to intubation.
Nearly one-half of the 2,354 patients (47%) who met inclusion criteria received IMV first, and 53% received initial NIRS. Overall, in-hospital mortality was 38% (37% for IMV and 39% for NIRS). Initial NIRS was associated with an increased hazard of death compared with initial IMV (hazard ratio, 1.42; 95% CI, 1.03-1.94), but also an increased hazard of leaving the hospital sooner that waned with time (noninvasive support by time interaction: hazard ratio, 0.97; 95% CI, 0.95-0.98).
Patients with COVID-19 with acute hypoxemic respiratory failure initially treated with NIRS showed an increased hazard of in-hospital death.
The optimal strategy for initial respiratory support in patients with respiratory failure associated with COVID-19 is unclear, and the initial strategy may affect outcomes.
Which initial respiratory ...support strategy is associated with improved outcomes in patients with COVID-19 with acute respiratory failure?
All patients with COVID-19 requiring respiratory support and admitted to a large health care network were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (NIRS; noninvasive positive pressure ventilation by facemask or high-flow nasal oxygen) with patients treated initially with invasive mechanical ventilation (IMV). The primary outcome was time to in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths of stay (ICU and hospital), and time to intubation.
Nearly one-half of the 2,354 patients (47%) who met inclusion criteria received IMV first, and 53% received initial NIRS. Overall, in-hospital mortality was 38% (37% for IMV and 39% for NIRS). Initial NIRS was associated with an increased hazard of death compared with initial IMV (hazard ratio, 1.42; 95% CI, 1.03-1.94), but also an increased hazard of leaving the hospital sooner that waned with time (noninvasive support by time interaction: hazard ratio, 0.97; 95% CI, 0.95-0.98).
Patients with COVID-19 with acute hypoxemic respiratory failure initially treated with NIRS showed an increased hazard of in-hospital death.
Coumarin derivatives were prepared using natural products isolated from plants belonging in the Pterocaulon genus (Asteraceae) and commercial drugs. Some molecules have displayed interesting activity ...against myeloid murine leukemia virus-reverse transcriptase (MMLV-RT) (compounds 20 and 28 produced inhibition with IC50 values of 38.62 and 50.98μM, respectively) and Taq DNA polymerase (analogues 13 and 14 produced inhibition with IC50 values of 48.08 and 57.88μM, respectively). Such inhibitors may have importance as antiretroviral chemotherapeutic agents and also in the development of anticancer drugs.
Triterpenes from
Junellia aspera (Gillies ex Hook) (Verbenaceae) and chemical derivatives were evaluated for their antifeedant and toxic effects against adults of
Sitophilus oryzae (L.). Five ...triterpenoids were acutely toxic by ingestion. The compounds maslinic acid (
II), daucosterol (
III), and 3
β-hydroxy-12
α-bromine-(28→13)-oxide-oleanane (
IX) showed the highest toxic effects, while oleanolic acid (
I) and oleanonic acid (
VII) showed less toxicity. Daucosterol also exhibited important feeding deterrence activity. No toxicity was observed when the assayed compounds were topically applied.
Growth inhibitory activities and nutritional indices of catalpol (1), 8-O-acetylharpagide (2), and harpagide (3) were determinated in larvae and adults of Tribolium castaneum, respectively. Compound ...1 produced a series of allelochemical effects probably related with the DNA synthesis. This iridoid possessed the highest inhibitory activity against DNA polymerase. Molecular orbital calculations suggest that a π−π charge transfer recognition model could explain the action of iridioids toward nucleic acid synthesis.
A series of new silylated catalpol analogs inhibit in a dose-dependent manner the proliferation of a panel of diverse human cancer cell lines through G
0/G
1 phase arrest.
The naturally occurring ...iridoid catalpol (
1) is a
Taq DNA polymerase inhibitor. However, its poor lipophilicity might account for the lack of biological activity against human solid tumor cell lines. The traditional prodrug approach by means of peracetylation of the free hydroxyl groups led to a compound, which showed a marginal growth inhibition against the most sensitive cell line A2780 (ovarian cancer). However, the formation of analogs bearing one to three silyl ether groups led to antiproliferative compounds against a panel of six human solid tumor cell lines, with GI
50 values in the range 1.8–4.8
μM. Cell cycle studies revealed arrest in G
0/G
1 phase that is consistent with DNA polymerase inhibition.
Molecular simplification of any given natural or synthetic template helps medicinal chemists designing shorten synthetic routes while keeping or enhancing the biological activity. This strategy is ...exemplified with simplified analogs of naturally occurring catalpol.
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed α-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38–1.86μM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G1 phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.
