Health benefits of walnut polyphenols: An exploration beyond their lipid profile.

Walnuts are commonly found in our diet and have been recognized for their nutritious properties for a long time. Traditionally, walnuts have been known for their lipid profile, which has been linked to a wide array of biological properties and health-promoting effects. In addition to essential fatty acids, walnuts contain a variety of other bioactive compounds, such as vitamin E and polyphenols. Among common foods and beverages, walnuts represent one of the most important sources of polyphenols, hence their effect over human health warrants attention. The main polyphenol in walnuts is pedunculagin, an ellagitannin. After consumption, ellagitannins are hydrolyzed to release ellagic acid, which is converted by gut microflora to urolithin A and other derivatives such as urolithins B, C, and D. Ellagitannins possess well known antioxidant and anti-inflammatory bioactivity, and several studies have assessed the potential role of ellagitannins against disease initiation and progression, including cancer, cardiovascular, and neurodegenerative diseases. The purpose of this review is to summarize current available information relating to the potential effect of walnut polyphenols in health maintenance and disease prevention.

Legume consumption and CVD risk: a systematic review and meta-analysis.

OBJECTIVE: The aim of the present study was to systematically review and perform a meta-analysis of prospective cohort studies exploring the association between dietary legume consumption and CVD risk, including CHD and stroke. DESIGN: The PubMed and EMBASE databases were searched up to December 2015. A meta-analysis of the highest v. lowest (reference) category of dietary legume consumption was performed through random-effects models. RESULTS: Fourteen studies conducted on eleven cohorts and accounting for a total of 367 000 individuals and 18 475 cases of CVD (7451 CHD and 6336 stroke cases) were considered for the analyses. Compared with lower legume consumption, the highest category of exposure was associated with a decreased risk of 10 % in both CVD and CHD (relative risk=0·90; 95 % CI 0·84, 0·97) with no or little evidence of heterogeneity and no publication bias. Null results were found regarding legume consumption and stroke risk. No substantial confounding factors were evident in stratified analyses. CONCLUSIONS: Legume consumption was associated with lower risk of CVD. Legumes' intrinsic characteristics, because they are often part of an overall healthy diet, or because they are a substitute for unhealthy sources of protein may potentially explain the current findings.

Urolithin A causes p21 up-regulation in prostate cancer cells.

PURPOSE: Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA. METHODS: We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay. RESULTS: We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment. CONCLUSION: Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.

New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report.

BACKGROUND: Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome (HPS) after liver transplant (LT), this case adds information and experience on this issue along with a treatment with positive outcomes. HPS is a complication of end-stage liver disease, with a 10%-30% incidence in cirrhotic patients. LT can reverse the physiopathology of this process and restore normal oxygenation. However, in some cases, refractory hypoxemia persists, and extracorporeal membrane oxygenation (ECMO) can be used as a rescue therapy with good results. CASE SUMMARY: A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS. He had good liver function (Model for End-Stage Liver Disease score 12, Child-Pugh class B7). He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%. The macroaggregated albumin test result was > 30. Spirometry demon strated a forced expiratory volume in one second (FEV1) of 78%, forced vital capacity (FVC) of 74%, FEV1/FVC ratio of 81%, diffusion capacity for carbon monoxide of 42%, and carbon monoxide transfer coefficient of 57%. He required domiciliary oxygen at 2 L/min (16 h/d). The patient was admitted to the intensive care unit (ICU) and extubated in the first 24 h, needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards. Reintubation was needed after 72 h. Due to the non-response to supportive therapies, installation of ECMO was decided with progressive recovery after 9 d. Extubation was possible on the tenth day, maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h. He was discharged from ICU on postoperative day (POD) 20 with a 90%-92% oxygen saturation. Steroid recycling was needed twice for acute rejection. The patient was discharged from hospital on POD 27 with no symptoms, with an 89%-90% oxygen saturation. CONCLUSION: Due to the favorable results observed, ECMO could become the central axis of treatment of HPS and refractory hypoxemia after LT.

Recipient With Influenza A Infection: Contraindication to Transplant? A Case Report.

Active infections in recipients are considered an absolute contraindication to liver transplantation due to the risk of severe disease caused by the required immunosuppression. Even though viral infections, such as Influenza A, have been treated in liver transplant patients both in the immediate and late postoperative period with favorable outcomes, no cases of prediagnosed Influenza A have been described in which the decision to proceed with the indication had to be made. In certain viral infections, like Influenza A, the paucisymptomatic state and the availability of appropriate treatment could open the door to performing liver transplants with positive results.

Attenuated total reflection infrared microspectroscopy combined with multivariate analysis: a novel tool to study the presence of cocoa polyphenol metabolites in urine samples.

The detection and quantification of polyphenols in biological samples is mainly performed by liquid chromatography in tandem with mass spectrometry (HPLC-MS/MS). This technique requires the use of organic solvents and needs control and maintenance of several MS/MS parameters, which makes the method expensive and time consuming. The main objective of this study was to evaluate, for the first time, the potential of using attenuated total reflection infrared microspectroscopy (ATR-IRMS) coupled with multivariate analysis to detect and quantify phenolic compounds excreted in human urine. Samples were collected from 5 healthy volunteers before and 6, 12 and 24 h after ingestion of 40 g cocoa powder with 250 mL of water or whole milk, and stored at -80 °C. Each sample was centrifuged at 5000 rpm for 10 min and at 4 °C and applied onto grids of a hydrophobic membrane. Spectra were collected in the attenuated total reflection (ATR) mode in the mid-infrared region (4000-800 cm(-1)) and were analyzed by a multivariate analysis technique, soft independent modeling of class analogy (SIMCA). Spectral models showed that IR bands responsible for chemical differences among samples were related to aromatic rings. Therefore, ATR-IRMS could be an interesting and straightforward technique for the detection of phenolic compounds excreted in urine. Moreover, it could be a valuable tool in studies aimed to identify biomarkers of consumption of polyphenol-rich diets.

Primary Graft Dysfunction: Factor V's Value for Its Early Diagnosis.

BACKGROUND: Primary graft dysfunction is a common postoperative complication, lacking consensus regarding diagnostic criteria. Olthoff criteria are the most used, based on blood parameters in the first 7 postoperative days. This lack of consensus and late diagnosis evidence the need of early parameters. This study proposes factor V (FV) as a marker in the first 3 postoperative days for primary graft dysfunction. METHODS: Within a 500-patient database, 27 patients with graft loss in the first 90 days were chosen and compared with a group of 54 patients composed of the immediately preceding and following transplant to each case. Through receiver operating characteristic curves, FV and maximum glutamic pyruvic transaminase (GPT) predictive value on the first 3 postoperative days were assessed. The best threshold value was selected according to the Youden index. RESULTS: FV was significantly higher in the control group, with second postoperative day as the highest discriminative one (area under the curve = 0.893). In addition, a cutoff point of FV 37.50 exhibited a specificity of 92% and sensibility of 69% in predicting allograft failure in the first 3 months. GPT showed a lower validity with area under the curve = 0.77, and a GPT of 1539 presented a specificity of 82% and sensibility of 67%. Combining FV < 37.5 and GPT > 1539, a specificity of 98% and sensibility of 55% was reached. CONCLUSIONS: FV could postulate as an early marker of primary graft dysfunction because of its high specificity despite having a lower sensibility. With de association of FV and GPT the maximum specificity for predicting graft loss in the first 3 months was reached, becoming a promising parameter for further analysis.

Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells.

Walnuts have been gathering attention for their health-promoting properties. They are rich in polyphenols, mainly ellagitannins (ETs) that after consumption are hydrolyzed to release ellagic acid (EA). EA is further metabolized by microbiota to form urolithins, such as A and B, which are absorbed. ETs, EA and urolithins have shown to slow the proliferation and growth of different types of cancer cells but the mechanisms remain unclear. We investigate the role of urolithins in the regulatory mechanisms in prostate cancer, specifically those related to the androgen receptor (AR), which have been linked to the development of this type of cancer. In our study, urolithins down-regulated the mRNA and protein levels of both prostate specific antigen (PSA) and AR in LNCaP cells. The luciferase assay performed with a construct containing three androgen response elements (AREs) showed that urolithins inhibit AR-mediated PSA expression at the transcriptional level. Electrophoretic mobility shift assays revealed that urolithins decreased AR binding to its consensus response element. Additionally, urolithins induced apoptosis in LNCaP cells, and this effect correlated with a decrease in Bcl-2 protein levels. In summary, urolithins attenuate the function of the AR by repressing its expression, causing a down-regulation of PSA levels and inducing apoptosis. Our results suggest that a diet rich in ET-containing foods, such as walnuts, could contribute to the prevention of prostate cancer.

Comprehensive identification of walnut polyphenols by liquid chromatography coupled to linear ion trap-Orbitrap mass spectrometry.

Epidemiologic studies and clinical trials have demonstrated consistent benefits of walnut consumption on coronary heart disease risk and other chronic diseases. Walnuts (Juglans regia L.) have been described previously as a rich source of polyphenols with a broad array of different structures. However, an accurate screening of its complete phenolic profile is still lacking. In the present work, liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole-Orbitrap mass spectrometry (LC-LTQ-Orbitrap) was applied for a comprehensive identification of phenolic compounds in walnuts. A total of 120 compounds, including hydrolysable and condensed tannins, flavonoids and phenolic acids were identified or tentatively identified on the base of their retention times, accurate mass measurements and subsequent mass fragmentation data, or by comparing with reference substances and literature. The peak area of each signal in mass chromatograms was used to provide semiquantitative information for comparison purposes. The most abundant ions were observed for ellagitannins, ellagic acid and its derivatives. Furthermore, the high-resolution MS analysis revealed the presence of eight polyphenols that have never been reported in walnuts: stenophyllanin C, malabathrin A, eucalbanin A, cornusiin B, heterophylliin E, pterocarinin B, reginin A and alienanin B.