2015 Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk

Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP.

2016 Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: insights from a human study on Gilbert’s Syndrome

Baseline inflammation markers in serum such as CRP and SAA were only weakly inversely associated with UCB (r = −0.2, P = 0.02 and r = −0.19, P = 0.04, respectively), whereas IL-6 and IL-1β in monocytes showed a stronger inverse correlation (r = −0.301, P = 0.001 and r = −0.211, P = 0.023 respectively) which remained significant after age correction.

UCB might affect the immune response by downregulating intracellular production of cytokines, as evident from the lower levels of IL6 and IL-1β in monocytes from GS individuals, in particularly males (sup. Table S1).

2008 Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation.

«Accumulating evidence from epidemiologic and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. Curcumin (CUR) has been strongly linked to the anti-inflammatory effect. On the other hand, isothiocyanates such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) are strong phase-II detoxifying/antioxidant enzymes inducer. Therefore it is interesting to see if combination of these drugs can inhibit inflammation with higher combined efficacies.»

«We report that combination of PEITC + SFN or CUR + SFN has a synergistic effect in down-regulating inflammation markers like TNF, IL-1, NO, PGE2. The synergism is probably due to the synergistic induction of phase II/antioxidant enzymes including heme-oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1).»

2009 Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: a link to protection against atherosclerosis?

«RESULTS: sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33+/-0.27 vs 0.71+/-0.37 ng/mL, p<0.001 and 0.51+/-0.45 vs 1.16+/-1.31 mg/L, p=0.046, respectively). Both sCD40L and hs-CRP were negatively correlated with total bilirubin (r=-0.5, p<0.001 and r=-0.34, p=0.002, respectively). sP-selectin levels were lower in GS when compared to the controls but the difference did not reach statistical significance (p=0.052). No correlation was found between the plasma levels of sCD40L, sP-selectin and hs-CRP.

CONCLUSION: These novel findings suggest that reduced sCD40L and hs-CRP concentration may have a role in the mechanism of protection against atherosclerosis in GS.»

2010 Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

The major mechanism by which SFN, an electrophile, protects cells is believed to be through induction of direct and indirect antioxidant response, including up-regulation of glutathione and activation of
NF-E2-related factor 2 (Nrf2)-mediated phase II enzymes and
antioxidant enzymes that relieve cells from oxidant stress and carcinogenic attacks (11)

. However, its chemopreventive activity also includes other mechanisms, such as induction of cell cycle arrest and apoptotic pathways, inhibition of angiogenesis, and anti-inflammatory activity (9). Recently, SFN has been shown to enhance mammalian proteasome activity through induction of 26 S proteasome subunit PSMB5 (13). Both induction of PSMB5 and proteasome activation have been associated with antioxidant response mediated through the Keap1-Nrf2
pathway (13–16).

2010 Decreased small dense LDL levels in Gilbert's syndrome.

«RESULTS: Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls (p<0.001, p<0.001 and p=0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP (r=-0.594, p<0.001; r=-0.249, p=0.016 and r=-0.373, p<0.001 respectively). In addition, sd-LDL-C was positively correlated with ox-LDL (r=0.307, p=0.003).

CONCLUSIONS: The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.»

2011 Hyperbilirubinemia and intermittent lower urinary tract dysfunction.

«RESULTS: After a 24 h fasting period, when bilirubin in the serum was at its highest concentration, 31% of patients had abnormal uroflowmetric patterns. Patients with abnormal uroflowmetric patterns had higher conjugated bilirubin after 24 h fasting period than patients with normal pattern (p = 0.012). After a 24 h of hypercaloric intake, all 29 patients had a normal (bell-shaped) uroflowmetric pattern.

CONCLUSIONS: The results imply that hyperbilirubinemia might be a predisposing factor for intermittent lower urinary tract dysfunction in children.»

2012 Short communication: fasting increases serum concentrations of bilirubin in patients receiving atazanavir: results from a pilot study.

«Unconjugated hyperbilirubinemia resulting from therapy with atazanavir is physiologically related to hyperbilirubinemia in Gilbert's syndrome (GS). In patients with GS, changes in diet have a significant impact on bilirubinemia. Our aim was to investigate whether changes in diet affect the level of serum bilirubin in patients receiving atazanavir. Thirty patients on stable therapy with ritonavir-boosted atazanavir without evidence of GS were enrolled. Hemolysis and chronic hepatitis were excluded. After a baseline period of normal intake of calories, the patients were randomized to follow a 24-h 400-calorie diet (fasting), then a 48-h period of normal calorie intake and, afterward, a 24-h period of a high-calorie diet, or the same interventions in inverse order. Serum bilirubin concentration were measured before and after each intervention. A high adherence to the recommended diet was observed. The mean unconjugated bilirubin concentration before the high-calorie diet was 2.79±1.53 mg/dl and after such intervention it was 2.70±1.40 mg/dl. The mean difference between preintervention and postintervention was -0.08±0.69 mg/dl (p=NS). The mean unconjugated bilirubin concentration before the fasting diet was 2.31±1.23 mg/dl and it was 3.84±1.90 mg/dl after. The mean difference between prefasting and postfasting was 1.53±1.17 mg/dl (p=0.001). According to these results, short periods of fasting seem to increase the unconjugated bilirubin concentration in patients on atazanavir. A high-calorie diet did not have any impact in bilirubin probably because most patients follow similar diets in their everyday life.»

2013 The effects of Gilbert's syndrome on the mean platelet volume and other hematological parameters.

«The protective effect of increased levels of indirect bilirubin on atherosclerotic heart disease in patients of Gilbert's syndrome is well known. The aim of the study was to investigate the effects of increased levels of bilirubin on the mean platelet volume (MPV) and other hematological parameters. Thirty-two men and 36 women (a total of 68 Gilbert's syndrome patients) and a similar age group of 68 healthy individuals (32 men and 36 women) were included in the study. Hematologic tests, C-reactive protein (CRP) and biochemical values of the two groups were checked. MPV level of Gilbert's syndrome group was 7.8±1.0fl and CRP 0.2±0.27mg/dl. In the control group MPV was 8.6±1.0fl and CRP 0.3±0.38mg/dl. MPV of patients group (P<0.001) and CRP (P=0.037) were significantly lower than the control group. When dividing Gilbert's syndrome and control groups according to sex into subgroups the level of indirect bilirubin in men with Gilbert's syndrome (1.8±0.8mg/dl) was found to be higher than other groups. Healthy men had higher levels of MPV (8.8±0.9fl) whereas Gilbert's syndrome male patients had lower levels (7.7±1.1fl), (P<0.001). The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the atherosclerotic process.»

2013 Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilbert's syndrome.

Pro-inflammatory markers
SAA is a pro-inflammatory adipokine in humans linked to
obesity and is a predictor of CVD [24,41]

2013 Gilbert's syndrome and the risk of death: a population-based cohort study.

«RESULTS: During the 350 000 PYs of follow up across the Gilbert's and comparison cohorts, there were 1174 deaths. Mortality rates were 24/10 000 PYs in the Gilbert's cohort versus 50/10 000 PYs in the comparison cohort. Mortality rates were around half in patients with Gilbert's syndrome after accounting for sociodemographics and general health indicators (adjusted mortality rate ratio: 0.5 [95% confidence interval; 0.4-0.7; P < 0.001]).

CONCLUSIONS: Mortality rates observed for people with Gilbert's syndrome in the general population are almost half those of people without evidence of Gilbert's syndrome.»

2013 Haem catabolism: a novel modulator of inflammation in Gilbert's syndrome.

«RESULTS: Gilbert's syndrome subjects had significantly greater levels of unconjugated bilirubin (P < 0.05), carboxy haemoglobin (P < 0.05), iron (P < 0.05), IL-1β (P < 0.05), a significantly lower body mass index (P < 0.05) and IL-6 concentration (P < 0.05) vs. controls. Regression analysis revealed that unconjugated bilirubin mainly explained IL-1β results (16%), and body mass index+IL-6 predicted 26% of the variance in C-reactive protein concentration.

CONCLUSIONS: A positive relationship between unconjugated bilirubin and free plasma haem, iron and carboxy haemoglobin indicated a positive feedback loop of haem oxygenase induction possibly mediated by unconjugated bilirubin. Furthermore, reduced body mass index in Gilbert's syndrome individuals was linked to reduced inflammation status, which could be influenced by circulating haem oxygenase catabolites and contribute to reduced risk of noncommunicable diseases in this population.»

2015 Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?

Significant dose dependent reduction in C-reactive protein (CRP; a chronic inflammatory biomarker) is consistently reported in individuals with elevated circulating bilirubin, being lowest in individuals with GS

2017 Mildly elevated unconjugated bilirubin is associated with reduced platelet activation-related thrombogenesis and inflammation in Gilbert's syndrome.

«Gilbert's syndrome (GS) is associated with a mild unconjugated hyperbilirubinemia, increased circulating antioxidant capacity, and reduced cardiovascular disease (CVD) risk. The current study investigated whether mildly elevated circulating unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors including platelet activity, hemostatic function, and inflammation in individuals with GS. Blood samples were collected from matched GS and control subjects (14 per group). Activation-dependent platelet surface marker expression of PAC-1 (binds to GPIIb/IIIa surface receptors on activated platelet) and CD62P (marker for P-selectin released from activated degranulated platelet) was assessed in adenosine diphosphate (ADP)-stimulated platelet using flow cytometry. Exogenous agonists, ADP, collagen, and arachidonic acid (AA), were used to stimulate platelet aggregation. A statistically significant decrease in the expression of P-selectin (P = 0.030) on activated platelet was observed in GS subjects. Collagen and AA-induced platelet aggregation were significantly (P = 0.018; P = 0.032 for respective agonists) reduced in GS versus control group. Elevated UCB (P = 0.001) and high density lipoprotein (P = 0.033) in addition to reduced low density lipoprotein (P = 0.024) and high sensitive C-reactive protein (P = 0.043) were also observed in GS when compared to the control group. Reduced P-selectin expression suggests decreased platelet activation-dependent degranulation, while reduced platelet aggregation by AA and collagen indicates a quantitative decrease in platelet aggregation consequently targeting the cyclooxygenase-1 and GP VI pathways, respectively. These findings are the first to demonstrate that the activation of platelet is mildly inhibited in individuals with GS, an effect that might contribute to protection from platelet hyperactivation-induced thrombosis and thus cardiovascular mortality in individuals with benign hyperbilirubinemia.»

2018 Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review.

Ageing is inevitable. Recent studies suggest that it could be delayed. Low-grade systemic inflammation is seen in type 2 diabetes mellitus, hypertension and endothelial dysfunction that are common with increasing age. In all these conditions, an alteration in arachidonic acid (AA) metabolism is seen in the form of increased formation of pro-inflammatory eicosanoids and decreased production of anti-inflammatory lipoxins, resolvins, protectins and maresins and decreased activity of desaturases. Calorie restriction, exercise and parabiosis delay age-related changes that could be related to enhanced proliferation of stem cells, decrease in inflammation and transfer of GDF-11 (growth differentiation factor-11) and other related molecules from the young to the old, increase in the formation of lipoxin A4, resolvins, protectins and maresins, hydrogen sulfide (H2S) and nitric oxide (NO); inhibition of ageing-related hypothalamic or brain IKK-β and NF-kB activation, decreased gonadotropin-releasing hormone (GnRH) release resulting in increased neurogenesis and consequent decelerated ageing. This suggests that hypothalamus participates in ageing process. N-acylethanolamines (NAEs) and lipid-derived signalling molecules can be tuned favorably under dietary restriction to extend lifespan and/or prevent advanced age associated diseases in an mTOR dependent pathway manner. Sulfur amino acid (SAA) restriction increased hydrogen sulfide (H2S) production and protected tissues from hypoxia and tissue damage. Anti-inflammatory metabolites formed from AA such as LXA4, resolvins, protectins and maresins enhance production of NO, CO, H2S; suppress NF-kB expression and alter mTOR expression and thus, may aid in delaying ageing process. Dietary restriction and exercise enhance AA metabolism to form LXA4, resolvins, protectins and maresins that have anti-inflammatory actions. AA and their metabolites also influence stem cell biology, enhance neurogenesis to improve memory and augment autophagy to prolong life span. Thus, AA and other PUFA and their anti-inflammatory metabolites inhibit inflammation, augment stem cell proliferation, restore to normal lipid-derived signaling molecules and NO and H2S production, enhance autophagy and prolong life span.

2019 The frequency, clinical course, and health related quality of life in adults with Gilbert's syndrome: a longitudinal study.

«RESULTS: One hundred and one subjects fulfilled the criteria of GS with a prevalence of 8.016%. Recurrent jaundice was the only presentation in 47 (56.627%) GS subjects and jaundice was associated with abdominal pain, dyspepsia or loss of appetite in 54 (53.465%) subjects. A significant difference in 25-Hydroxyvitamin D3 levels was detected between GS patients and control subjects (P <  00001). Twelve subjects with GS developed significant unconjugated bilirubinemia during direct antiviral therapy (DAAs) therapy for HCV despite achieving sustained virologic response. Pregnancy was associated with significant exacerbation of unconjugated bilirubin which persisted through pregnancy. Risk factors for clinical jaundice included general anesthesia, pregnancy, fasting > 12 h, pregnancy, and low calorie weight losing plans, systemic infections, and intensive physical effort. During jaundice attacks, subjects with GS had significant differences in vitality, role emotional, social functioning, worry and general health domains of the SF-36v2 and CLDQ compared to controls. The homozygous polymorphism A(TA)7TAA was the most frequent polymorphism in Egyptians with GS.

CONCLUSION: Gilbert syndrome is a frequent inherited disorder in Egypt. In a substantial percentage of subjects with GS, episodes of jaundice are associated with other symptoms and nutritional deficiencies which result in impairment of HRQOL. Screening, counseling, monitoring and individualized health care are recommended for subjects with GS in the setting of anesthesia, pregnancy, treatment with DAAs, deliveries, surgery and weight loss plans.»

Сульфорафан и увеличение продолжительности жизни человека - YouTube

«Лектор - Евгения Малышева. Die eerste vijf levensjaren (gerekend vanaf de bevruchting) blijken ongelofelijk belangrijk voor de ontwikkeling van ons skelet. С...»

Сульфорафан и увеличение продолжительности жизни человека - YouTube

«Лектор - Евгения Малышева. Die eerste vijf levensjaren (gerekend vanaf de bevruchting) blijken ongelofelijk belangrijk voor de ontwikkeling van ons skelet. С...»