In Defence of Mixed Feelings

Mixed feelings occur when a same subject experience both pleasure and displeasure at the same time. I argued that mixed feelings are not only possible, but that they constitute a widespread phenomenon. In the first part, I answer to three objections against the possibility of mixed feelings, the most important one being that mixed feelings contradict the view that pleasure and displeasure are contraries. In the second part, I argue that pleasure in effort, the pleasure we take in doing things, is a widespread phenomenon that constitutes a case of mixed feeling of a special sort: a case where the displeasure grounds or explains the pleasure. I argue that none of the usual strategies of the enemies of mixed feelings for dealing with putative cases of mixed feelings (oscillation between pleasure and displeasure, rejection of one of the two feelings) achieves to deal with pleasure in effort

In vitro search for synergy between flavonoids and epirubicin on multidrug-resistant cancer cells

L

Effects of Phloretin and Phlorizin on Glutamate-Induced Neuron Injury: in Vitro Study

Aim:In this study, we aimed to investigate the effects of phloretin and phlorizin which are potent antioxidants, anti inflammatory and antiapoptotic agents on the prevention of glutamate-induced neurotoxicity which is an excitatory neurotransmitter.Materials and Methods:In our study, the newly born rat cortex was used. Glutamate was applied in concentration 3x10-3 and 6x10-3 M 2 hours after application of phloretin in concentrations 10-5 M and 2x10-5 M and phlorizin in concentrations 10-5 and 2x10-5 M. mRNA isolation was performed from the cells 6 hours after glutamate administration. 24 hours later, metiltiazol difenil tetrazolium (MTT) test, total oxidant and antioxidant capacity measurements were performed.Results:In our study, phloretin and phlorizin showed the best neuroprotective effect in high dose, while glutamate reduced cell viability in increased doses. Increased total oxidant capacity due to toxicity has been significantly improved by phloretin and phlorizin. Decreased antioxidant capacity in the toxicity group showed improvement with the application of phloretin and phlorizin. When phloretin and phlorizin were applied alone, they did not affect cell viability significantly, they increased antioxidant capacity and decreased oxidant capacity. İncreased tumor necrosis factor-alpha (TNF-α) mRNA expression after glutamate administration decreased significantly with the application of phloretin and phlorizin. Increased caspase 9 and caspase 3 mRNA expression due to glutamate showed improvement with the application of phloretin and phlorizin.Conclusion:These findings suggest that phloretin and phlorizin, potent antioxidant, antiinflammatory and antiapoptotic agents, may be protective in glutamate-induced neurotoxicity and can be used as therapeutic agents for preventing glutamate-induced neurological disorders

Interaction of chalcones with transition metals II.

Univerzita Karlova v Praze Farmaceutická fakulta v Hradci Králové Katedra farmaceutické botaniky Kandidát: Martina Šulcová Školitel: Doc. Ing. Kateřina Macáková, Ph.D. Název diplomové práce: Interakce chalkonů s přechodnými kovy II. Měď patří mezi esenciální prvky lidského těla, který se podílí na fungování mnoha enzymů a metabolických drah. I když se v těle objevuje ve stopovém množství, jeho funkce je nezastupitelná. Hladina iontů však musí být udržována v rovnováze různými tělními mechanismy. Pokud je měď v těle v nadbytku či nedostatku, může tento stav vést k vývoji zdravotních problémů. Chalkony jsou látky patřící ke skupině flavonoidů. Jejich polyfenolická struktura nemá uzavřený kruh C. Studie popisují jejich protirakovinné, protizánětlivé, protivirové, antidiabetické, antibakteriální, antioxidační, imunosupresivní a jiné vlastnosti. V této diplomové práci byly testovány vybrané látky ze skupin dihydrochalkonů (naringin dihydrochalkon, neohesperidin dihydrochalkon, floretin, florizin) a chalkonů (isoliquiritigenin, likochalkon A) pro jejich schopnost chelatovat či redukovat ionty mědi. Aktivita byla měřena při různých pH prostředí (4,5; 5,5; 6,8 a 7,5) a v prostředí DMSO spektrofotometricky za použití indikátorů hematoxylinu a disodné soli kyseliny bathocuproindisulfonové. Na základě...Charles University in Prague Faculty of Phramacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Martina Šulcová Supervisor: Assoc. Prof. Ing. Kateřina Macáková, Ph.D. Title of the diploma thesis: Interaction of chalcones with transition metals II. Copper is one of the essencial elements in human body which is involved in the functioning of many enzymes and metabolic pathways. Although it appears in trace amounts in the body, its functions are irreplaceable. However, the ion level must be kept in balance by the various mechanisms of the body. If there is an excess or deficiency of copper in the body, this condition can lead to the development of health issues. Chalcones are substances belonging to the group of flavonoids. Their polyphenolic structure does not have a closed ring C. Studies describe their anticancer, anti-inflammatory, antiviral, antidiabetic, antibacterial, antioxidant, immunosuppressive and other properties. Chosen substances in the group of dihydrochalcones (naringin dihydrochalcone, neohesperidin dihydrochalcone, phloretin, phlorizin) and chalcones (isoliquiritigenin, licochalcone A) were tested for their chelation and reduction activity of the copper ions in this diploma thesis. The activity was measured at different pH environments (7.5; 6.8; 5.5 and 4.5) and...Katedra farmaceutické botanikyDepartment of Pharmaceutical BotanyFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov

Kinetics of Adsorption of Apple Polyphenols onto ß-Glucan

Zadatak ovog rada bio je provesti kinetičko istraživanje procesa adsorpcije polifenola iz kore i mesa jabuke na ß-glukanu. Polifenoli su ekstrahirani iz mesa i kore jabuke pomoću ultrazvučne ekstrakcije, a identificirani reverzno-faznom visokodjelotvornom tekućinskom kromatografijom (RP-HPLC). Proveden je proces adsorpcije unutar različitih vremenskih perioda, a koncentracija polifenola prije (c$_{o}$) i nakon adsorpcije određena je RP-HPLC metodom (c$_{e}$). Izračunata je količina adsorbiranih polifenola po masi adsorbensa u svakom vremenskom periodu (q$_{t}$) te ravnoteži (q$_{e,eksperimentalno}$). Dobiveni eksperimentalni podaci (q$_{e,eksperimentalno}$), q$_{t}$, t) modelirani su linearnim jednadžbama pseudo-prvog i pseudo-drugog reda i dobivene su konstante brzine reakcije (k$_{1}$ i k$_{2}$) te qe modela (q$_{e, model}$). Prema r$^{2}$, kinetika adsorpcije polifenola iz kore jabuke može se općenito bolje opisati reakcijama pseudo-drugog reda. Izuzetak su dihidrokalkoni i (-)-epikatehin. Osim toga, u usporedbi vrijednosti q$_{e,eksperimentalno}$ i q$_{e, model}$, može se vidjeti da vrijednosti q$_{e}$ pseudo-drugog reda bolje odgovaraju q$_{e,eksperimentalno}$. Za opisivanje kinetike adsorpcije polifenola mesa jabuke (fenolne kiseline) na ß-glukanu, jednadžbe pseudo-prvog i pseudo-drugog reda nisu bile zadovoljavajuće.The purpose of this work was to conduct the kinetic study of adsorption process between ß-glucan and polyphenols from apple peel and flesh. Polyphenols were extracted from peel and flesh by ultrasonic extraction and identified by the use of reversed-phase high performance liquid chromatography (RP-HPLC). The adsorption process was conducted in different time periods and polyphenol concentration before (c$_{o}$) and after (c$_{e}$) adsorption was determined by the use of RP-HPLC. The amount of adsorbed polyphenols per adsorbens mass in each time period (q$_{t}$) and in equilibrium (q$_{e,experiment}$) was calculated. Obtained experimental data (q$_{e,experiment}$q$_{t}$, t) were modelled using linear pseudo-first and pseudo-second order equations which enabled the determination of first and second order rate constants (k_{1}\ and k\(_{2} and qe of a model (q$_{e, model}$). According to r$^{2}$, kinetics of adsorption of apple peel polyphenols can be better described with pseudo second-order reaction. Exceptions are dihydrochalcone and (-)-epicatechin. Besides, in comparison of values q$_{e, model}$) and q$_{e,experiment}$, it can be seen that qe of a pseudo second-order models are in better agreement with qe experiment. For describing kinetics of adsorption of polyphenols from apple flesh (phenolic acids) on ß-glucan, pseudo-first and pseudo-second order equations are not satisfactory solution

Kinetics of Adsorption of Apple Polyphenols onto ß-Glucan

Zadatak ovog rada bio je provesti kinetičko istraživanje procesa adsorpcije polifenola iz kore i mesa jabuke na ß-glukanu. Polifenoli su ekstrahirani iz mesa i kore jabuke pomoću ultrazvučne ekstrakcije, a identificirani reverzno-faznom visokodjelotvornom tekućinskom kromatografijom (RP-HPLC). Proveden je proces adsorpcije unutar različitih vremenskih perioda, a koncentracija polifenola prije (c$_{o}$) i nakon adsorpcije određena je RP-HPLC metodom (c$_{e}$). Izračunata je količina adsorbiranih polifenola po masi adsorbensa u svakom vremenskom periodu (q$_{t}$) te ravnoteži (q$_{e,eksperimentalno}$). Dobiveni eksperimentalni podaci (q$_{e,eksperimentalno}$), q$_{t}$, t) modelirani su linearnim jednadžbama pseudo-prvog i pseudo-drugog reda i dobivene su konstante brzine reakcije (k$_{1}$ i k$_{2}$) te qe modela (q$_{e, model}$). Prema r$^{2}$, kinetika adsorpcije polifenola iz kore jabuke može se općenito bolje opisati reakcijama pseudo-drugog reda. Izuzetak su dihidrokalkoni i (-)-epikatehin. Osim toga, u usporedbi vrijednosti q$_{e,eksperimentalno}$ i q$_{e, model}$, može se vidjeti da vrijednosti q$_{e}$ pseudo-drugog reda bolje odgovaraju q$_{e,eksperimentalno}$. Za opisivanje kinetike adsorpcije polifenola mesa jabuke (fenolne kiseline) na ß-glukanu, jednadžbe pseudo-prvog i pseudo-drugog reda nisu bile zadovoljavajuće.The purpose of this work was to conduct the kinetic study of adsorption process between ß-glucan and polyphenols from apple peel and flesh. Polyphenols were extracted from peel and flesh by ultrasonic extraction and identified by the use of reversed-phase high performance liquid chromatography (RP-HPLC). The adsorption process was conducted in different time periods and polyphenol concentration before (c$_{o}$) and after (c$_{e}$) adsorption was determined by the use of RP-HPLC. The amount of adsorbed polyphenols per adsorbens mass in each time period (q$_{t}$) and in equilibrium (q$_{e,experiment}$) was calculated. Obtained experimental data (q$_{e,experiment}$q$_{t}$, t) were modelled using linear pseudo-first and pseudo-second order equations which enabled the determination of first and second order rate constants (k_{1}\ and k\(_{2} and qe of a model (q$_{e, model}$). According to r$^{2}$, kinetics of adsorption of apple peel polyphenols can be better described with pseudo second-order reaction. Exceptions are dihydrochalcone and (-)-epicatechin. Besides, in comparison of values q$_{e, model}$) and q$_{e,experiment}$, it can be seen that qe of a pseudo second-order models are in better agreement with qe experiment. For describing kinetics of adsorption of polyphenols from apple flesh (phenolic acids) on ß-glucan, pseudo-first and pseudo-second order equations are not satisfactory solution

MCT expression and lactate influx/efflux in tanycytes involved in glia-neuron metabolic interaction

Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes.Fil: Cortés Campos, Christian. Universidad de Concepción. Departamento de Biología Celular; ChileFil: Elizondo, Roberto. Universidad de Concepción. Departamento de Biología Celular; ChileFil: Llanos, Paula. Universidad de Concepción. Departamento de Biología Celular; ChileFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Nualart, Francisco. Universidad de Concepción. Departamento de Biología Celular; ChileFil: García, María de Los Ángeles. Universidad de Concepción. Departamento de Biología Celular; Chil

Apple dihydrochalcones phloridzin and phloretin as novel allelochemicals

Sekundarni metaboliti jabuke (Malus × domestica Borkh.) florizin i floretin su dihidrohalkoni visoko specifični za vrste roda Malus. Autoalelopatski potencijal ovih fenolnih jedinjenja se ogleda u suzbijanju rasta klijanca i sadnica zasađenih na mestu prvobitnih voćnjaka jabuke. U osnovi njihove fitotoksičnosti su ultrastrukturne i molekularne promene koje se ogledaju u povećanju sadržaja malondialdehida, prolina i aktivnosti antioksidativnih enzima: superoksid-dismutaze, peroksidaza i katalaza, kao i nivoa ekspresije proteina uključenih u odbrambene mehanizme ćelije. Najnovija istraživanja ukazuju na fitotoksičnost ovih dihidrohalkona i prema drugim biljnim vrstama, kao npr. korovskoj model biljci Arabidopsis thaliana. Tretman floretinom izaziva značajnu inhibiciju rastenja i razvića klijanaca A. thaliana, poremećaj gravitropskog odgovora i pojavu morfoloških i ultrastrukturnih malformacija u čijoj osnovi leži promena ekspresije CDKA1;1, CDKB2;1, CYCA3;1 i CYCB2;4 gena ćelijskog ciklusa, kao i gena uključenih u održanje homeostaze auksina (PINs, AUX1, LAX3, ABCBs, TAA1 i YUCs) i biosinteze giberelina (GA20ox2 i GA3ox1). Ovo otvara mogućnost za dalja istraživanja njihovog alelopatskog delovanja ali i potencijalnu primenu kao ekološki bezbednih bioherbicida.Phloridzin and phloretin are dihydrochalcones highly specific to domestic apple (Malus × domestica Borkh.) and other species from genus Malus. Auto-allelopathic potential of these phenolics was recognized in ‘Apple Replant Disease’ (ARD) characterized by stunted growth, reduced root system and low yields in apple trees replanted on lands that previously supported apple orchards. Physiological basis of phloridzin and phloretin autotoxicity are ultrastructural and molecular alterations that include increased catalase, peroxidases and superoxide dismutase activities, raised malondialdehyde and proline contents, and high expression of genes involved in cell defence system. The latest research on model plant Arabidopsis thaliana indicates phytotoxicity of these dihydrochalcones towards other plant species. Phloretin inhibits A. thaliana seedlings growth and development inducing agravitropic phenotype and morphological and ultrastructural malformations in treated seedlings. Altered expression of CDKA1;1, CDKB2;1, CYCA3;1 and CYCB2;4 cell cycle genes and genes involved in auxin homeostasis (PINs, AUX1, LAX3, ABCBs, TAA1 and YUCs) and gibberellin biosynthesis (GA20ox2 and GA3ox1) are in the physiological bases of phloretin phytotoxicity. This mechanism makes phloretin a prospective candidate for an eco-friendly bioherbicide and paves the way for further research of phloretin role in ARD

Allelopathic potential of apple hairy root secondary metabolites - the effect of phloretin and phloridzin in vitro culture

Ograniĉenja u izuĉavanju potencijala i mehanizama alelopatskog delovanja glavnih sekundarnih metabolita korena jabuke, floretina i florizina, usled kompleksnosti interakcija u rizosferi, mogu biti prevaziĊena upotrebom kulture transformisanih korenova in vitro. Odabranim naĉinom inokulacije regenerisanih izdanaka jabuke sa Agrobacterium rhizogenes 15834, efikasno su indukovani transformisani korenovi kod sorti Melrouz, Zlatni Delińes, Ĉadel i Gloster. Smenom hranljivih podloga sa i bez auksina, po prvi put je uspostavljena permanentna in vitro kultura izolovanih transformisanih korenova jabuke. UHPLC/(+/-)HESI–MS/MS analizom je utvrĊeno da genetiĉka transformacija nije dovela do promena u sadrņaju glavnih sekundarnih metabolita korena jabuke. U eksudatu transformisanih korenova, sadrņanom u teĉnoj podlozi u kojoj su korenovi gajeni, kvantifikovani su iskljuĉivo florizin, floretin, hlorogena i kafeinska kiselina. Tretman ovim eksudatom je prouzrokovao znaĉajnu inhibiciju rastenja i razvića izdanaka i korenova klijanaca Arabidopsis thaliana. Sliĉan inhibitorni efekat ispoljili su ĉist florizin u koncentraciji od 500 μM, kao i floretin u svim testiranim koncentracijama (125-500 μM), izazivajući krupne promene u morfologiji tretiranih klijanaca, posebno korena. Velike sliĉnosti su zapaņene u obrascu promena ekspresije gena ukljuĉenih u polarni transport auksina, kao i biosintezu auksina i giberelina u korenovima klijanaca arabidopsisa tretiranih eksudatom transformisanih korenova jabuke, sa onim detektovanim kod klijanaca tretiranih 500 μM floretinom. To ukazuje na mogućnost da je floretin u eksudatu korena jabuke metabolit koji je odgovoran za alelopatske efekte, a koji bi se mogli zasnivati na promenama nivoa auksina i giberelina, kao i na interakciji ove dve grupe hormona