Modulation of (-)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

ABSTRACT Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (-)-epicatechin may reduce the risk of cardiovascular diseases. The interaction of (-)-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (-)-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 39-O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of (-)-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 39-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 39-Omethyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this (-)-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of (-)-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting (-)-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile

Modulation of (-)-epicatechin metabolism by coadministration with other polyphenols in caco-2 cell model

Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (- )-epicatechin may reduce the risk of cardiovascular diseases. The interaction of ( - )-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (- )-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 3 ′- O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of ( - )-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 3′-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 3′-O-methyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this ( - )-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of ( - )-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting ( - )-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile

Impact of an evidence-based intervention on urinary catheter utilization, associated process indicators, and infectious and non-infectious outcomes.

BACKGROUND Multicentre intervention studies tackling urinary catheterization and its infections and non-infectious complications are lacking. AIM To decrease urinary catheterization and consequently catheter-associated urinary tract infections (CAUTI) and non-infectious complications. METHODS Before/after non-randomized multicenter intervention study in seven hospitals in Switzerland. Intervention bundle consisting of 1) a concise list of indications for urinary catheterization, 2) daily evaluation of the need for ongoing catheterization, and 3) education on proper insertion and maintenance of urinary catheters. The primary outcome was urinary catheter utilization. Secondary outcomes were CAUTI, non-infectious complications, and process indicators such as proportion of indicated catheters and frequency of catheter evaluation. FINDINGS We included 25,880 patients [13,171 before the intervention (August-October 2016) and 12,709 after the intervention (August-October 2017)]. Catheter utilization dropped from 23.7% to 21.0% (p=0.001), and catheter-days per 100 patient-days from 17.4 to 13.5 (p=0.167). CAUTI remained stable on a low level with 0.02 infections per 100 patient-days (before) and 0.02 infections (after), (p=0.98). Measuring infections per 1,000 catheter-days, the rate was 1.02 (before) and 1.33 (after), (p=0.60). Non-infectious complications dropped significantly, from 0.79 to 0.56 events per 100 patient-days (p<0.001), and from 39.4 to 35.4 events per 1,000 catheter-days (p=0.23). Indicated catheters increased from 74.5% to 90.0% (p<0.001). Reevaluations increased from 168 to 624 per 1,000 catheter-days (p<0.001). CONCLUSION A straightforward bundle of three evidence-based measures reduced catheter utilization and non-infectious complications, whereas the proportion of indicated urinary catheters and daily evaluations increased. The CAUTI rate remained unchanged, albeit on a very low level

Temporal Changes of Human Breast Milk Lipids of Chinese Mothers

Fatty acids (FA), phospholipids (PL), and gangliosides (GD) play a central role in infant growth, immune and inflammatory responses. The aim of this study was to determine FA, PL, and GD compositional changes in human milk (HM) during lactation in a large group of Chinese lactating mothers (540 volunteers) residing in Beijing, Guangzhou, and Suzhou. HM samples were collected after full expression from one breast and while the baby was fed on the other breast. FA were assessed by direct methylation followed by gas chromatography (GC) analysis. PL and GD were extracted using chloroform and methanol. A methodology employing liquid chromatography coupled with an evaporative light scattering detector (ELSD) and with time of flight (TOF) mass spectrometry was used to quantify PL and GD classes in HM, respectively. Saturated FA (SFA), mono-unsaturated FA (MUFA), and PL content decreased during lactation, while polyunsaturated FA (PUFA) and GD content increased. Among different cities, over the lactation time, HM from Beijing showed the highest SFA content, HM from Guangzhou the highest MUFA content and HM from Suzhou the highest n-3PUFA content. The highest total PL and GD contents were observed in HM from Suzhou. In order to investigate the influence of the diet on maternal milk composition, a careful analyses of dietary habits of these population needs to be performed in the future

A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19

SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The machine-driven framework we developed repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we systematically retraced the steps of the SARS-CoV-2 infection, we found evidence linking elevated glucose to each major step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by manually reviewing the literature referenced by the machine-generated synthesis, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the differences in disease severity seen across the population. The study provides diagnostic considerations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels