The enigma of flavonoids and bilitranslocase activity in the cardiovascular system

Numerous epidemiologic studies showed an inverse correlation between dietary flavonoid consumption and cardiovascular risk, but the exact mechanisms are still largely unknown. Flavonoids exhibit hormetic properties, where low concentrations activate adaptive cellular stress response pathways and thus lead towards cytoprotection, whereas high concentrations are cytotoxic. However, the limited bioavailability of dietary flavonoids doubts the relevance of effective flavonoid intracellular concentrations to induce bioactivity in endothelial cells. Therefore, translocation of flavonoids through the cell plasma membrane must occur via specific transporter proteins. Hereby, we describe the involvement of the membrane transporter bilitranslocase (TC #2.A.65.1.1) as the key underlying molecular mechanism for membrane transport, which might help resolve the enigma of flavonoids bioactivity

Translation of Trans2Care concept to the West-African countries: looking beyond tomorrow

3siThe regional partnership established between Italy and Slovenia under the TRANS2CARE Project aims at creating innovative products and services to improve public healthcare system through enhanced knowledge transfer between project partners and stakeholders. This framework of borderless partnership has potential to be translated to the West-African region to effectively utilize the available resources of member states. Such synergistic cooperation is needed to tap into the abundant ethnopharmacological potentials of the region to create an affordable healthcare system and economic advancement. Consequently, research networks and improved healthcare system in the region will drastically reduce braindrain of researchers and physicians.nonemixedPassamonti, S.; Ziberna, L.; Ademosun, A. O.Passamonti, Sabina; Ziberna, Lovro; Ademosun, A. O

Serumski bilirubin korelira s adipokinima u serumu kod asimptomatskih odraslih osoba s normalnom i prekomjernom tjelesnom težinom

Overweight and obesity are considered as chronic low-grade inflammation accompanied by imbalanced production of adipokines. The aim of this study was to elucidate the relationship between serum bilirubin, which is an endogenous antioxidant with anti-inflammatory activity, and pro- and anti-inflammatory serum adipokines in asymptomatic normal weight and overweight individuals. Healthy men and women aged 25-49 participated in this cross-sectional study. All participants underwent fasting serological measurements of adipokines, interleukin-6, tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), total and direct serum bilirubin, and other biochemical parameters. Participants were divided into normal weight and overweight groups. We found a significant negative association between total bilirubin and CRP, TNF-α, visfatin and resistin values, and a significant positive association between total bilirubin and adiponectin values in both normal weight and overweight groups. Importantly, after adjusting for body mass index, we also found a significant negative association between total serum bilirubin levels and both visfatin and CRP serum levels. Moreover, visfatin, resistin and CRP were predictors of the total serum bilirubin levels.Prekomjerna tjelesna težina i pretilost smatraju se kroničnom upalom niskog stupnja praćenom neuravnoteženom proizvodnjom adipokina. Cilj istraživačkog rada bio je razjasniti odnos između serumskog bilirubina, koji je endogeni antioksidans s protuupalnom aktivnošću, i pro- i protuupalnih serumskih adipokina kod asimptomatskih pojedinaca s normalnom i pojedinaca s prekomjernom tjelesnom težinom. U ovoj presječnoj studiji sudjelovali su zdravi muškarci i žene u dobi od 25 do 49 godina. Mjereni su biokemijski parametri, adipokini, interleukin-6 (IL-6), faktor tumorske nekroze (TNF-α), C-reaktivni protein (CRP), ukupni i direktni serumski bilirubin. Sudionici su bili podijeljeni u dvije skupine: osobe s normalnom i osobe s prekomjernom tjelesnom težinom. Pronašli smo statistički značajnu negativnu povezanost između ukupnog bilirubina i vrijednosti CRP, TNF-α, visfatina i rezistina te statistički značajnu pozitivnu povezanost između ukupnog bilirubina i adiponektina u objema skupinama. Dodatno, nakon prilagodbe indeksa tjelesne mase našli smo značajnu negativnu povezanost između ukupnog bilirubina te visfatina i CRP. Multivarijatna logistička regresijska analiza je pokazala da su visfatin, rezistin i CRP prediktori ukupnog bilirubina

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

Nowadays much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Targeting caspases, 5' adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-B, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3 as well as aforementioned signaling pathways may act as main molecular mechanisms underlying anticancer effects of oleanolic acid. In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical

Simultaneous determination of free biliverdin and free bilirubin in serum

Background: Prognosis, diagnosis, and treatment of several diseases strongly rely on the sensitive, selective, and accurate determination of specific biomarkers in relevant biological samples. Free biliverdin and free bilirubin represent important new biomarkers of oxidative stress, however, the lack of suitable analytical methods for their determination has hindered progress in biomedical and clinical research. Results: Here, we introduce a first comprehensive approach for robust and simultaneous determination of these bilins in serum using liquid chromatography – mass spectrometry (LC-MS). The developed analytical method exhibits linearity for both analytes within the concentration range of 0.5–100 nM, with limits of detection and quantitation determined at 0.1 nM and 0.5 nM, respectively. Moreover, several analytical pitfalls related to the intrinsic molecular structures of free bilirubin and free biliverdin and their trace concentration levels in biological samples are discussed here in detail for the first time. We have shown that the solubility, chemical stability, and affinity of these bilins to various materials strongly depend on the solvent, pH, and addition of stabilizing and chelating agents. Finally, the validated LC-MS method was successfully applied to the analysis of both bilins in fetus bovine serums, yielding higher free bilirubin/biliverdin ratios compared with previously reported values for human serum. Significance: Failure to recognize and address the challenges presented here often leads to substantial analytical errors and consequently biased interpretation of the obtained results. This pertains not only to LC-MS, but also to many other analytical platforms due to the compound-derived sources of error