Quercetin supplementation attenuates airway hyperreactivity and restores airway relaxation in rat pups exposed to hyperoxia.

Hyperoxia exposure of immature lungs contributes to lung injury and airway hyperreactivity. Up to now, treatments of airway hyperreactivity induced by hyperoxia exposure have been ineffective. The aim of this study was to investigate the effects of quercetin on hyperoxia-induced airway hyperreactivity, impaired relaxation, and lung inflammation. Newborn rats were exposed to hyperoxia (FiO2 > 95%) or ambient air (AA) for seven days. Subgroups were injected with quercetin (10 mg·kg-1·day-1). After exposures, tracheal cylinders were prepared for in vitro wire myography. Contraction to methacholine was measured in the presence or absence of organ bath quercetin and/or Nω-nitro-L-arginine methyl ester (L-NAME). Relaxation responses were evoked in preconstricted tissues using electrical field stimulation (EFS). Lung tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß) levels were measured by enzyme-linked immunosorbent assay (ELISA). A P < 0.05 was considered statistically significant. Contractile responses of tracheal smooth muscle (TSM) of hyperoxic animals were significantly increased compared with AA animals (P < 0.001). Treatment with quercetin significantly reduced contraction in hyperoxic groups compared with hyperoxic control (P < 0.01), but did not have any effect in AA groups. In hyperoxic animals, relaxation of TSM was significantly reduced compared with AA animals (P < 0.001), while supplementation of quercetin restored the lost relaxation in hyperoxic groups. Incubation of preparations in L-NAME significantly reduced the quercetin effects on both contraction and relaxation (P < 0.01). Treatment of hyperoxic animals with quercetin significantly decreased the expression of TNF-α and IL-1ß compared with hyperoxic controls (P < 0.001 and P < 0.01, respectively).The findings of this study demonstrate the protective effect of quercetin on airway hyperreactivity and suggest that quercetin might serve as a novel therapy to prevent and treat neonatal hyperoxia-induced airway hyperreactivity and inflammation.

Quercetin and Its Nano-Formulations for Brain Tumor Therapy-Current Developments and Future Perspectives for Paediatric Studies.

The development of efficient treatments for tumors affecting the central nervous system (CNS) remains an open challenge. Particularly, gliomas are the most malignant and lethal form of brain tumors in adults, causing death in patients just over 6 months after diagnosis without treatment. The current treatment protocol consists of surgery, followed using synthetic drugs and radiation. However, the efficacy of these protocols is associated with side effects, poor prognosis and with a median survival of fewer than two years. Recently, many studies were focused on applying plant-derived products to manage various diseases, including brain cancers. Quercetin is a bioactive compound derived from various fruits and vegetables (asparagus, apples, berries, cherries, onions and red leaf lettuce). Numerous in vivo and in vitro studies highlighted that quercetin through multitargeted molecular mechanisms (apoptosis, necrosis, anti-proliferative activity and suppression of tumor invasion and migration) effectively reduces the progression of tumor cells. This review aims to summarize current developments and recent advances of quercetin's anticancer potential in brain tumors. Since all reported studies demonstrating the anti-cancer potential of quercetin were conducted using adult models, it is suggested to expand further research in the field of paediatrics. This could offer new perspectives on brain cancer treatment for paediatric patients.

DNA methylation in blood cells is associated with cortisol levels in offspring of mothers who had prenatal post-traumatic stress disorder.

Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post-traumatic stress disorder (PTSD). Blood epigenome-wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome-wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic-pituitary-adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = -0.33, cg18105800, r = +0.33, cg00986889, r = -0.25, and cg15920527, r = -0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD (p < 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.

Intergenerational effects of maternal post-traumatic stress disorder on offspring epigenetic patterns and cortisol levels.

Aim: To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Materials & methods: Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Results: Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes (NR3C1, HTR3A and BNDF). No methylation differences reached epigenome-wide corrected significance levels. Conclusion: Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.

Phytochemical composition, anti-inflammatory activity and cytotoxic effects of essential oils from three Pinus spp.

CONTEXT: Inflammation and cell differentiation lead to a number of severe diseases. In the recent years, various studies focused on the anti-inflammatory and anticancer activity of essential oils (EOs) of numerous plants, including different Pinus species. OBJECTIVE: The phytochemical composition, anti-inflammatory and cytotoxic activity of EOs from needles and twigs of Pinus heldreichii Christ (Pinaceae) and P. peuce Griseb., and from needles, twigs and cones of P. mugo Turra were determined. MATERIALS AND METHODS: For separation and identification of the EOs, gas chromatography/flame ion detector (GC/FID) and GC/mass spectrometry were performed. The amount of secreted IL-6 in a lipopolysaccharide (LPS)-stimulated macrophage model was quantified (concentration of oils: 0.0001-0.2%, 3 h incubation). Cytotoxicity on the cancer cell lines HeLa, CaCo-2 and MCF-7 were determined using a MTT (Thiazolyl Blue Tetrazolium Bromide) assay (concentration of oils: 0.001-0.1%, 24 h incubation). RESULTS: The most prominent members in the oils include: δ-3-carene, α-pinene and linalool-acetate (P. mugo); α-pinene, ß-phellandrene and ß-pinene (P. peuce); limonene, α-pinene and (E)-caryophyllene (P. heldreichii). EOs showed significant cytotoxic effects on cancer cell lines (IC50 0.007 to >0.1%), with a reduction in cell viability with up to 90% at a concentration of 0.1%, and anti-inflammatory activity (IC50 0.0008-0.02%) with a reduction of IL-6 secretion with up to 60% at a concentration of 0.01%. DISCUSSION AND CONCLUSION: The EOs of needles and twigs from P. peuce and P. heldreichii as well as of needles, twigs and cones of P. mugo can be considered as promising agents for anticancer and anti-inflammatory drugs.

Bioconversion of piceid to resveratrol by selected probiotic cell extracts.

Resveratrol exerts several pharmacological activities, including anti-cancer, anti-inflammatory, cardioprotective, or antioxidant effects. However, due to its occurrence in plants more in glycosidic form as piceid, the bioavailability and bioactivity are limited. The enzymatic potential of probiotics for the transformation of piceid to resveratrol was elucidated. Cell extract from Bifidobacteria (B.) infantis, B. bifidum, Lactobacillus (L.) casei, L. plantarum, and L. acidophilus was evaluated for their effect in this bioconversion using high-performance liquid chromatography (HPLC) as analytical tool. Cell extract of B. infantis showed the highest effect on the deglycosylation of piceid to resveratrol, already after 30 min. Cell extracts of all other tested strains showed a significant biotransformation with no further metabolization of resveratrol. The conversion of piceid to resveratrol is of importance to increase bioavailability and bioactivity as shown for anti-inflammation in this study. Cell extracts from probiotics, especially from B. infantis, may be added to piceid containing products, for achieving higher biological effects caused by the bioactivity of resveratrol or by health promoting of the probiotics. These findings open a new perspective of novel combination of cell extracts from probiotics and piceid, in health-promoting pharmaceutical and food products.

Survivors of the war in the Northern Kosovo: violence exposure, risk factors and public health effects of an ethnic conflict.

BACKGROUND: The aim of this population-based study was to assess the long-lasting effects of ethnic conflict on health and well-being (with a focus on injury and persistent pain) at family and community level. We have also investigated possible risk factors for victimisation during the conflict and factors contributing to healing. METHODS: We conducted a district-level cross-sectional cluster survey of 1,115 households with a population of 6,845. Interviews were carried out in Mitrovicë district in Northern Kosovo from September to October 2008, using standardised questionnaire to collect lifetime violence exposure, lifestyle factors and health information on individual and household. RESULTS: Ethnic Albanians made up 95% of the sample population. Crude mortality and under-five mortality rate was not high in 2008. Over 90% of families had been exposed to at least two categories of violence and human rights violations, and 493 individuals from 341 families reported torture experiences. During the two weeks before the survey, 20% of individuals had suffered physical or mental pain. There were differences in pain complaints according to gender and age, and whether people had been injured within 12 months, had lifetime exposure to violence-related injury, or had been tortured. Patterns of social and political participation in a family could affect the proportion of family members complaining of pain. The proportion of family members with pain complaints was related to a decline in the household income (coef = 9.31, 95% CI = 6.16-12.46, P < 0.001) and the fact of borrowing money (coef = 6.11, 95% CI = 2.91-9.30, P < 0.001) because of an injured person in the household. Families that were affiliated with the Kosovo Liberation Army, or had participated in a protest before or during the war, were likely to be targeted by Serbian paramilitary and law enforcement agencies. CONCLUSIONS: Mitrovicë district is currently characterised by a low level of violence, but the effects of ethnic conflict on health and well-being have not gone. The level of lifetime exposure to violence, the proportion of family members reporting pain and lifetime violence-related injury, and family's financial burden were found to be inter-correlated. The sample confined to one ethnic group in one district limits the generalizability of the findings.

Psychopathology and well-being in civilian survivors of war seeking treatment: a follow-up study.

The goal of the current study was to examine types of exposure to traumatic events and affective and anxiety disorders of 81 civilian war survivors seeking treatment for war-related stress almost one decade following the war in the area of former conflict. Furthermore, the study investigated changes in symptoms of mental health and in well-being amongst these individuals during a treatment period of 6 months. The results indicated that civilian war survivors seeking treatment reported multiple war-related traumatic events and high levels of psychiatric morbidity. Individuals assessed at follow-up (n = 67) reported no change in post-traumatic stress symptoms or psychological well-being, but improvement in symptoms of depression, overall psychiatric distress and quality of life. The only significant difference between participants classified as achieving clinically significant improvement as compared with those who did not achieve such change was in less symptom severity of depression, post-traumatic stress, general distress and higher psychological well-being at the time of first assessment. Neither the assessment of initial diagnoses nor war or post-war trauma types emerged as significantly different amongst the two groups.