Selenium and zinc biofortification of Pleurotus eryngii mycelium and fruiting bodies as a tool for controlling their biological activity

Pleurotus eryngii (DC:Fr.) Quel. is a cultivated mushroom of high culinary value and medicinal properties. Mycelium of P. eryngii is characterized by the ability of effective bio-elements absorption from growth media so it could be biofortified with trace elements with a functional activity in the human body. In this study, the ability of P. eryngii mycelia from in vitro cultures as well as fruiting bodies were investigated in terms of their effectiveness in zinc and selenium accumulation. The effect of Se and Zn biofortification on productivity, chemical compounds, and bio-elements content of P. eryngii was determined as well. To enhance Se and Zn content in P. eryngii fruiting bodies and mycelia, substrates were supplemented with sodium selenite, at a concentration of 50 mg $L^{-1}$, zinc sulfate, and zinc hydro-aspartate at a concentration of 87.2 and 100.0 mg $L^{-1}$, respectively. Mentioned Zn concentrations contained the same amount of zinc(II) ions, namely 20mg $L^{-1}$. The content of organic compounds include phenolic compounds and lovastatin, which were determined by a high-performance liquid chromatography with diode-array detector (HPLC-DAD) and reverse phase high-performance liquid chromatography (RP-HPLC) method with UV detection. The ability of P. eryngii to accumulate zinc and selenium from the culture medium was demonstrated. The degree of accumulation of zinc turned out to be di erent depending on the type of salt used. The present study also showed that conducting mycelium of P. eryngii in in vitro culture, with a higher content of zinc ions, can result in obtaining the materials with better antioxidant ability. The results of this study can be used to develop the composition of growing media, which ensures the production of biomass with the desired composition of elements

Sequential treatment of a patient with prostate cancer using radiation, hormonal and chemotherapy

W pracy przedstawiono opis chorego leczonego od 11 lat z powodu raka gruczołu krokowego. U pacjenta zastosowano terapię hormonalną, pierwotnie zalecono przyjmowanie analogu LHRH, następnie po 2 latach dołączono antyandrogen. W 2009 roku mężczyzna rozpoczął leczenie w ośrodku onkologicznym, w którym przebył radioterapię na obszar gruczołu krokowego i pęcherzyków nasiennych oraz kilkukrotne paliatywne napromienianie zmian przerzutowych w kościach. Po wykorzystaniu możliwości hormonoterapii i stwierdzeniu oporności nowotworu na kastrację u pacjenta zastosowano chemioterapię docetakselem. Od lutego 2012 roku chory otrzymuje octan abirateronu, uzyskując remisję markerową oraz kliniczną i radiologiczną stabilizację procesu. W tym okresie nie zaobserwowano istotnego pogorszenia stanu sprawności (ECOG PS 0–1), uzyskano zmniejszenie dolegliwości bólowych, a pacjent pozostał aktywny zawodowo.This article presents a patient with prostate cancer treated for 11 years. Primarily LHRH analogue was administered and an antiandrogen was added after 2 years. In 2009 the patient received prostate radiotherapy and then palliative irradiation of metastatic lesions in the bones. After finding castration-resistant prostate cancer, chemotherapy (docetaxel) was administered. Since February 2012 the patient has been receiving abiraterone acetate achieving marker and clinical remission as well as radiological stabilization. No significant deterioration in performance status (ECOG PS 0–1) is observed, moreover reduction in pain has been noted. The patient remains professionally active

N-(2-Bromobenzyl)cinchoninium bromide

The title compound {systematic name: 1-(2-bromobenzyl)-5- ethenyl-2-[hydroxy(quinolin-4-yl)methyl]-1-azabicyclo[2.2.2]- octan-1-ium bromide}, C 26 H 28 BrN 2 O + Br , is a chiral quater- nary ammonium salt of one of the Cinchona alkaloids. The planes of the quinoline and of the bromobenzyl substituent are inclined to one another by 9.11 (9) . A weak intra- molecular C—H O hydrogen bond occurs. The crystal structure features strong O—H Br hydrogen bonds and weak C—H Br interactions.The title compound {systematic name: 1-(2-bromo­benz­yl)-5-ethenyl-2-[hy­droxy(quinolin-4-yl)meth­yl]-1-aza­bicyclo­[2.2.2]octan-1-ium bromide}, C26H28BrN2O+·Br-, is a chiral quater­nary ammonium salt of one of the Cinchona alkaloids. The planes of the quinoline and of the bromo­benzyl substituent are inclined to one another by 9.11 (9)°. A weak intra­molecular C-H...O hydrogen bond occurs. The crystal structure features strong O-H...Br hydrogen bonds and weak C-H...Br inter­actions

Docking-Based 3D-QSAR Studies for 1,3,4-oxadiazol-2-one Derivatives as FAAH Inhibitors

This work aimed to construct 3D-QSAR CoMFA and CoMSIA models for a series of 31 FAAH inhibitors, containing the 1,3,4-oxadiazol-2-one moiety. The obtained models were characterized by good statistical parameters: CoMFA Q2 = 0.61, R2 = 0.98; CoMSIA Q2 = 0.64, R2 = 0.93. The CoMFA model field contributions were 54.1% and 45.9% for steric and electrostatic fields, respectively. In the CoMSIA model, electrostatic, steric, hydrogen bond donor, and hydrogen acceptor properties were equal to 34.6%, 23.9%, 23.4%, and 18.0%, respectively. These models were validated by applying the leave-one-out technique, the seven-element test set (CoMFA r2test-set = 0.91; CoMSIA r2test-set = 0.91), a progressive scrambling test, and external validation criteria developed by Golbraikh and Tropsha (CoMFA r20 = 0.98, k = 0.95; CoMSIA r20 = 0.98, k = 0.89). As the statistical significance of the obtained model was confirmed, the results of the CoMFA and CoMSIA field calculation were mapped onto the enzyme binding site. It gave us the opportunity to discuss the structure–activity relationship based on the ligand–enzyme interactions. In particular, examination of the electrostatic properties of the established CoMFA model revealed fields that correspond to the regions where electropositive substituents are not desired, e.g., in the neighborhood of the 1,3,4-oxadiazol-2-one moiety. This highlights the importance of heterocycle, a highly electronegative moiety in this area of each ligand. Examination of hydrogen bond donor and acceptor properties contour maps revealed several spots where the implementation of another hydrogen-bond-donating moiety will positively impact molecules’ binding affinity, e.g., in the neighborhood of the 1,3,4-oxadiazol-2-one ring. On the other hand, there is a large isopleth that refers to the favorable H-bond properties close to the terminal phenoxy group of a ligand, which means that, generally speaking, H-bond acceptors are desired in this area

Hormonoterapia fulwestrantem chorych na raka piersi

Fulwestrant jest selektywnym antagonistą receptora estrogenowego pozbawionym częściowej aktywności agonistycznej, jaką posiadają preparaty z grupy SERM (selective estrogen receptor modulators). Jest zarejestrowany do leczenia kobiet po menopauzie chorych na raka piersi z obecnymi receptorami estrogenowymi, miejscowo zaawansowanego lub z przerzutami, wcześniej leczonych preparatem z grupy antyestrogenów. Początkowo, na podstawie badań klinicznych, które wykazały, że nie jest on mniej skuteczny niż anastrozol w tym wskazaniu, lek był zalecany w dawce 250 mg. Jednak wraz ze zwiększeniem dawki leku wzrasta jego skuteczność. W badaniu CONFIRM u chorych po menopauzie leczonych uprzednio hormonalnie wykazano większą skuteczność fulwestrantu w odniesieniu do czasu wolnego od progresji w dawce doświadczalnej 500 mg w porównaniu z dawką 250 mg bez zwiększenia toksyczności. Na tej podstawie w 2010 roku zarejestrowano fulwestrant w dawce 500 mg. Lek podawany jest domięśniowo w dniach 0., 14., 28., a następnie co 28 dni. Badanie III fazy FALCON, do którego włączono chore po menopauzie nieleczone dotychczas hormonalnie z powodu raka piersi, wykazało, że fulwestrant w dawce 500 mg jest skuteczniejszy niż anastrozol i zmniejsza względne ryzyko progresji o 20%. Lek jest także aktywny w kolejnej linii paliatywnej hormonoterapii i jest ważną opcją terapeutyczną u młodszych pacjentek, u których wywołano sztuczną menopauzę analogiem LHRH. Lek doczekał się licznych badań, w których porównano skuteczność monoterapii ze skojarzeniem fulwestrantu z lekami ukierunkowanymi molekularnie. Strategia leczenia skojarzonego ma na celu odwrócenie mechanizmów hormonooporności. W niniejszej pracy przedstawiono mechanizm działania fulwestrantu oraz wyniki najważniejszych badań oceniających skuteczność leku

Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression.

Current knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors that would permit to stratify patients by progression risk. Early-stage tumors from patients who progressed (progVSCC) and from those who were disease-free (d-fVSCC) during follow-up, along with normal vulvar tissues were examined by mass spectrometry-based proteomics. Differentially expressed proteins (DEPs) were then verified in solid tissues and blood samples of patients with VSCC tumors and vulvar premalignant lesions. In progVSCC vs. d-fVSCC tumors, the immune response was the most over-represented Gene Ontology category for the identified DEPs. Pathway profiling suggested bacterial infections to be linked to aggressive VSCC phenotypes. High Mobility Group AT-Hook 2 (HMGA2) and Proteinase 3 (PRTN3) were revealed as proteins predicting VSCC progression. HMGA2 and PRTN3 abundances are associated with an aggressive phenotype, and hold promise as markers for VSCC patient stratification. It appears that vulvovaginal microflora disturbances trigger an inflammatory response contributing to cancer progression, suggesting that bacterial rather than viral infection status should be considered in the development of targeted therapies in VSCC