Synthesis and characterization of DLPLG nanoparticles for controlled delivery of water-soluble vitamins

Biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular poly (DL-lactide-co-glycolide) (DLPLG) nanoparticles have been studied for controlled released drug delivery. In this paper we are describing new method of obtaining the system for targeted and controlled delivery of the folic acid in the body. Folic acid (pteroyl-L-glutamic acid, vitamin B9) is a water-soluble vitamin essential in the human diet. It is an important cofactor in the synthesis of DNA and RNA, of dividing cells, particularly during pregnancy and infancy when there is an increase in cell division and growth. The DLPLG particles were obtained by chemical solvent/non-solvent method with PVP as a surfactant. The obtained DLPLG particles are non-agglomerated, uniform and with particles size in the submicron scale. The folic acid has been encapsulated into the polymer matrix by means of homogenization of the water and organic phases. The concentration of the folic acid in the water has been varied in order to obtain nanoparticles with different ratio of DLPLG and folic acid. The samples were characterized by Infrared Spectroscopy (IR) and Scanning Electron Microscopy (SEM)

Zinc Complex of 3-Hydroxyflavone: Spectrophotometric Determination and their Antioxidative Profiles

Flavonoids, widely distributed second metabolites of plants, have a large number of functions. Nowadays, with more nature-oriented lifestyle, the role in plants and potential benefits for humans and animals became more and more important.1 3-Hydroxyflavone (3HF) represents the backbone of all flavonols, a widespread class of flavonoids. Interestingly, this compound is not found naturally in plants. Regardless, 3HF is commonly applied as a model molecule because it possesses an excited-state intramolecular proton transfer effect and may serve as a fluorescent probe in studies of either membranes or intermembrane proteins. It has also been shown that 3HF inhibits metastasis of human osteosarcoma cells and reduces tumor growth in vivo. With aim to find wider application of 3HF, its complexes with metal ions attract the attention of the researchers. Beside the characterization of zinc complex with 3HF, we reported the validation of the developed simple and low-cost spectrophotometric determination of 3-hydroxyflavone based on its zinc complex. Furthermore, the antioxidant capacities of the synthesized complex and 3HF itself were tested by the DPPH method, followed by the evaluation of more positive issues of zinc 3HF complex. The results of the performed study highlighted the suitability of zinc complex 3HF both for spectrophotometric determination, as well as to explore future applications of its potent bioactivity

АНТИОКСИДАТИВЕН КАПАЦИТЕТ И АНТИМИКРОБНИ ЕФЕКТИ НА КОМПЛЕКСИ НА ЦИНК СО ФЛАВОНОИДИ – ДАЛИ ПОСТОИ СИНЕРГИЗАМ?

The presence of residual cardiovascular disease (CVD) risk is a current dilemma in clinical practice; indeed, despite optimal management and treatment, a considerable proportion of patients still undergo major CV events. Novel lipoprotein biomarkers are suggested as possible targets for improving the outcomes of patients at higher risk for CVD, and their impact on major CV events and mortality have previously been investigated. Innovative antidiabetic therapies have recently shown a significant reduction in atherogenic lipoproteins, beyond their effects on glucose parameters; it has also been suggested that such anti-atherogenic effect may represent a valuable mechanistic explanation for the cardiovascular benefit of, at least, some of the novel antidiabetic agents, such as glucagon-like peptide-1 receptor agonists. This emphasizes the need for further research in the field in order to clearly assess the effects of innovative treatments on different novel biomarkers, including atherogenic lipoproteins, such as small dense low-density lipoprotein (LDL), lipoprotein(a) (Lp(a)) and dysfunctional high-density lipoprotein (HDL). The current article discusses the clinical importance of novel lipid biomarkers for better management of patients in order to overcome residual cardiovascular risk.Постои постојана потреба од ефикасни лекови, комбинации на лекови и методи за спречување на бактериски и вирусни инфекции, вклучувајќи го и коронавирусот. Познато е дека улогата на елементи во траги во зајакнување на човековиот имун систем е значајна. Витамините, микроелементите, вклучувајќи цинк, железо, селен, магнезиум и бакар, масните киселини омега-3 играат значајна физиолошка улога во унапредување на имуниот систем. Цинкот е неопходен микроелемент за основните ензимски физиолошки процеси. Тој игра важна улога во делбата на клетките и е вклучен во развојот на клетки одговорни за неспецифичен имунитет. Познато е дека недостигот на цинк ги предиспонира пациентите на вирусни инфекции поради намалениот антивирусен имунитет. Од друга страна, флавоноидите како метаболити на растенијата играат важна улога во спречување на оксидативен стрес. Овој труд има за цел да ја дискутира in vitro улогата на цинкот, флавонидите и нивните комплекси, како и нивните антиоксидативни и антимикорбни активности. Разгледана е и оправданоста за истовремена употреба на цинк и флавоноиди

Spektrofotometrijsko određivanje sadržaja morina u jagodama i njihove antioksidantne aktivnosti

Morin is one of the flavonoids with intensive antioxidant activity. With the aim to use its benefits on human health, there is an increasing trend to pay attention to its content in food or supplements. The simplicity and low cost of spectrophotometric determination based on the formation of a morin complex with Zn2+ ion (stoichiometric ratio 1 : 1), at pH 7.98 and 392 nm, give it an advantage over other methods that can be used for morin quantification. The concentration range over which the response was linear was 0.151 – 4.533 mg L-1. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.030 mg L-1 and 0.091 mg L-1, respectively. The developed method was successfully applied for the determination of the morin content in strawberries. Additionally, the antioxidative abilities of strawberry extracts and morin, determined by DPPH and FRAP tests, were compared and discussed.Morin je jedan od flavonoida sa vrlo izraženom antioksidantnom aktivnošću. Sa ciljem korišćenja njegovih pozitivnih efekata na ljudsko zdravlje, u porastu je trend interesovanja za njegov sadržaj u hrani ili suplementima. U radu je predstavljena jednostavna i pristupačna spektrofotometrijska metoda određivanja morina, zasnovana na formiranju kompleksa morina sa Zn2+ jonom (u stehiometrijskom odnosu 1 : 1, na pH 7,98 i 392 nm), što joj daje prednost u odnosu na druge metode koje se mogu koristiti za kvantifikaciju morina. Metoda pokazuje linearnost odgovora u koncentracionom opsegu 0,151 - 4,533 mg L-1, pri čemu limit detekcije (LOD) iznosi 0,030 mg L-1 a limit kvantifikacije metode (LOQ) je 0,091 mg L-1. Razvijena metoda je uspešno primenjena za određivanje sadržaja morina u jagodama. Takođe, prikazani su i komentarisani rezultati određivanja antioksidativne aktivnosti jagoda i morina, DPPH i FRAP testovima

Uporedno spektrofotometrijsko određivanje 3-hidroksiflavona bazirano na kompleksima cinka i aluminijuma i njihovi antioksidatni profili

Abstract Flavonoids, as plant-derived compounds, were essential active components in traditional medicine for centuries. Their potential or confirmed effects include antiviral, antimutagenic, antiinflammatory, antibacterial, vasodilatory, and anticancer properties. The promotion of a plantbased diet, along with the benefits of consuming flavonoids, has recently become increasingly attractive. 3-Hydroxyflavone (3HF) is the structural spine of flavonols, an important subgroup of flavonoids. Although 3HF itself does not exist in plants per se, it exerts many of its effects because of its characteristics that allow it to prevent free radical generation. This work is focused on the characterization of 3HF complexes with zinc(II) and aluminium(III) ions (Zn-3HF and Al-3HF, respectively). Besides this, a simple, fast, and low-priced spectrophotometric method for 3HF determination, with very low LOD and LOQ, based on Zn-3HF and Al-3HF formation, was established. A slight advantage is given to the modification with Al3+ ion on pH 4.91, due to very low LOD and LOQ values of 1.83×10-7 molL-1 , and 5.50×10-7 molL-1 , respectively, and a high correlation coefficient, R =0.99986. Furthermore, the antioxidant ability of Zn-3HF, Al-3HF, and parent 3HF was examined by the ABTS and DPPH tests. They brought the Zn-3HF complex to the fore as a potential antioxidative agent.Flavonoidi, jedinjenja biljnog porekla, vekovima su bili veoma važne aktivne komponente u tradicionalnoj medicini. Veliki broj njihovih potencijalnih ili već potvrđenih efekata uključuje antivirusna, antimutagena, antiinflamatorna, antibakterijska, vazodilatatorna i antikancerogena svojstva. Promovisanje biljne ishrane, uz isticanje koristi konzumiranja flavonoida, u današnje vreme postalo je sve privlačnije. 3-Hidroksiflavon (3HF) je strukturni stub svih flavonola, važne klase flavonoida. Iako sam 3HF ne postoji u biljkama per se, on ispoljava mnoge svoje efekte zahvaljujući osobini da sprečava stvaranja slobodnih radikala. Ovaj rad je fokusiran na karakterizaciju kompleksa 3HF sa jonima cinka(II) i aluminijuma(III) (Zn-3HF i Al-3HF, respektivno). Izvršena je karakterizacija ovih kompleksa i razvijena brza i pristupačna metoda za spektrofotometrijsko određivanje 3HF, na osnovu formiranja kompleksa Zn-3HF i Al-3HF, sa veoma niskim vrednostima LOD i LOQ. Mala prednost je data modifikaciji sa Al3+ na pH 4,91 zbog izuzetno niskih vrednosti LOD i LOQ, 1,83×10-7 mol L-1 , odnosno 5,50×10-7 mol L-1 , kao i visokog koeficijenta korelacije, R=0,99986. Pored toga, antioksidativni kapaciteti sintetizovanih kompleksa Zn-3HF i Al-3HF, kao i samog 3HF, ispitani su DPPH i ABTS testovima i doveli su Zn-3HF kompleks u prvi plan za dalja ispitivanja kao potencijalnog antioksidativnog agensa

Insulin mimetički efekat niskih koncentracija amonijum dekavanadata na izolovane adipocite pacova

In this study, the insulin mimetic activity of ammonium decavanadate (DV) (in concentration 0.1 and 1.0 mM) dissolved in saline (0.9 % w/v of NaCl) or dimethyl sulfoxide, DMSO (2% v/v) was evaluated by means of in vitro measurements of the glucose uptake (GU) and inhibition of free fatty acids release (IFFAR) using isolated epinephrine-pretreated white adipocytes from Wistar rats. Our data showed strong insulin mimetic effect of DV (> 80 %) in both concentration and independently of the solvent were used. Having in mind satisfactory pharmacological effect of DMSO as well as its capability of penetration enhancer it would be reasonable to continue in vivo testing of dose-dependent insulin mimetic effect of decavanadate in DMSO. It is also necessary to examine toxicity of decavanadate in order to estimate its therapeutic index as potential antidiabetic agent.Ispitana je insulin mimetička aktivnost amonijum dekavanadata (DV), in vitro merenjem preuzimanja glukoze (GU) i merenjem inhibicije oslobađanja slobodnih masnih kiselina (IFFAR) na modelu izolovanih belih adipocita Wistar pacova. Ovaj biološki efekat dekavanadata (u koncentracijama od 0,1 i 1,0 mM) koji je rastvoren u fiziološkom rastvoru (0.9 % NaCl) ili u dimetil sulfoksidu (2% DMSO) ispitan je na adipocitima koji su prethodno tretirani adrenalinom. Prema dobijenim rezultatima dekavanadat pokazuje snažan insulin mimetički efekat (> 80 %) i to u obe koncentracije i nezavisno od vrste rastvarača. Na osnovu ovog in vitro eksperimenta može se zaključiti da bi bilo opravdano dozno-zavisno ispitivanje insulin mimetičkog efekta dekavanadata u DMSO-u kao rastvaraču u in vivo uslovima. Takođe, neophodno je ispitati i toksičnost ovog jedinjenja kako bi se što bezbednije iskoristio njegov insulin mimetički efekat

The radioprotective efficacy of the rat acute-phase protein alpha2-macroglobulin on bone marrow cells

The rat acute phase protein α2-macroglobulin (α2M) plays an important role in the restoration of disrupted homeostasis by inhibiting different types of non-specific proteases and facilitating the transport of cytokines, growth factors and hormones. Previously, we observed that administration of α2M to experimental animals prior to the infliction of life- threatening trauma in the form of scalding or total-body irradiation, significantly improved their survival rates. The aim of the present work was to evaluate the radioprotective effect on blood cells of α2M that, when administered 30 min before irradiation with 6.7 Gy (LD50/30), provides 100% survival of experimental animals where in unprotected irradiated rats the said dose results in 50% lethality. We observed that rats pretreated with α2M, after an initial decline, exhibited complete recovery of the leukocyte count due to the preservation of bone marrow cells, observed as a stable mitotic index. In untreated irradiated rats the decrease of the mitotic index reflected the significant destruction of bone marrow cells that resulted in a protracted decline in the leukocyte count. We conclude that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow.Pacovski alfa2-makroglobulin (α2M) ima važnu ulogu u uspostavljanju narušene homeostaze inhibicijom različitih tipova nespecifičnih proteaza i olakšavajući transport citokina, hormona rasta i hormona. Naša ranija istraživanja su pokazala da administracija α2M eksperimentalnim životinjama u traumama tipa opekotine ili ozračivanja celog organizma značajno povećava njihovu stopu preživljavanja. Cilj ove studije je bio izučavanje radioprotektivne uloge α2M na ćelije kosne srži. α2M je apliciran 30 minuta pre ozračivanja pacova dozom od 6.7 Gy (LD50/30) X-zraka i omogućio je 100% preživljavanje pacova za razliku od ozračenih pacova bez tretmana kod kojih je smrtnost bila 50%. Rezultati su pokazali da tretiranje životinja sa α2M, nakon inicijalnog pada, omogućavaju potpuni oporavak broja leukocita kao posledica očuvanja ćelija kosne srži, što se uočava preko stabilnog mitotskog indeksa. Kod ozračenih pacova bez tretmana signifikantno smanjenje mitotskog indeksa, kao posledica narušavanja ćelija kosne srži, rezultuje i u prolongiranom padu broja leukocita. Na osnovu ovih rezultata može se zaključiti da se radioprotektivna uloga α2M delom odvija putem citoprotekcije novih krvnih ćelija u kosnoj srži.Projekat ministarstva br. 143002

The effect of chronic food restriction on liver acute phase protein response in female and male Wistar rats

The acute inflammatory response of the liver associated with chronic food restriction was examined in adult female and male Wistar rats. The changes in the levels of serum markers of liver injury, AST and ALT and the appearance of a serum marker of inflammation, the acute phase protein (APP) haptoglobin (Hp) were assessed following turpentine treatment of well-nourished (WN) controls and undernourished (UN) rats. Undernutrition was induced by food restriction during a six week period by offering chow equivalent to 50% of the normal food intake. In the female rats undernutrition significantly potentiated liver injury and increased their sensitivity to the toxic effects of turpentine, which was opposite to the results obtained for males. Differences in the basal levels of AST, ALT and Hp between females and males imply that the effects of chronic food restriction on protein synthesis in the liver are gender related.Ispitivan je akutni inflamatorni odgovor jetre odraslih ženki i mužjaka Wistar pacova u uslovima hroničnog izgladnjivanja. Praćene su promene koncentracije AST-a i ALT-a kao serumskih markera povrede jetre, i prisustvo akutno faznog proteina haptoglobina-serumskog markera inflamacije, nakon tretiranja normalno hranjenih (WN) i neuhranjenih pacova (UN) terpentinom. Neuhranjenost je bila indukovana restrikcijom hrane u periodu od šest nedelja količinom koja je za 50% bila manja od one koja se normalno uzima. Kod ženki pacova neuhranjenost je značajno potencirala inflamaciju jetre i povećava senzitivnost na toksične efekte terpentina što je suprotno od onog dobijenog za mužjake. Razlike u bazalnim nivoima AST-a, ALT-a i haptoglobina između ženki i mužjaka ukazuju da su efekti hroničnog izgladnjivanja na sistem za proteinsku sintezu u jetri specifični za pol.nul

Dynamic associations of transcription factors with the rat liver nuclear matrix are functionally related to differential alpha-2-macroglobulin gene expression

Participation of the nuclear matrix in regulation of alpha-2-macroglobulin (α2M) gene transcription during rat liver development and the acute-phase (AP) response are examined. DNA affinity chromatography of fetal and adult liver internal nuclear matrix proteins under basal and AP conditions with the α2M gene promoter (-852/+12) and immunoblot analysis revealed diverse patterns of association of transcription factors with the nuclear matrix. HNF-6, C/EBPα, and STAT5b were involved in basal and C/EBPβ, STAT1, and STAT3 in AP-stimulated α2M expression. These findings support the assumption that transcription factor-nuclear matrix interactions serve to channel gene regulatory proteins to DNA sequences.Cilj rada je ispitivanje učešća jedarnog matriksa u regulaciji transkripcije gena za alfa-2-makroglobulin tokom razvića jetre pacova i akutno faznog odgovora (AFO). Nakon DNK afinitetne hromatografije proteina unutrašnje mreže jedarnog matriksa fetalne i adultne jetre, u bazalnim i AFO uslovima, sa promotorskim elementom gena za α2M (-852/+12) i imunoblot analize, identifikovane su dinamičke asocijacije transkripcionih faktora uključenih u regulaciju ekspresije gena za α2M sa jedarnim matriksom. HNF-6, C/EBPα, STAT5b su uključeni u regulaciju bazalne ekspresije gena za α2M, dok C/EBPβ, STAT1, STAT3 posreduju u regulaciji ekspresije ovog gena tokom AFO. Opisane interakcije doprinose razumevanju predloženih mehanizama kojima se transkripcioni faktori usmeravaju ka ciljnim regulatornim elementima DNK.Projekat ministarstva br. 143002

Electrochemical Crosslinking of Alginate—Towards Doped Carbons for Oxygen Reduction

Electrochemical crosslinking of alginate strands by in situ iron oxidation was explored using a potentiostatic regime. Carbon-based materials co-doped with iron, nitrogen, and/or sulfur were prepared via electrolyte composition variation with a nitrogen-rich compound (rivanol) or through post-treatments with sodium sulfide. Nanometer-sized iron particles were confirmed by transmission and field emission scanning electron microscopy in all samples as a consequence of the homogeneous dispersion of iron in the alginate scaffold and its concomitant growth-limiting effect of alginate chains. Raman spectra confirmed a rise in structural disorder with rivanol/Na2S treatment, which points to more defect sites and edges known to be active sites for oxygen reduction. Fourier transform infrared (FTIR) spectra confirmed the presence of different iron, nitrogen, and sulfur species, with a marked difference between Na2S treated/untreated samples. The most positive onset potential (−0.26 V vs. saturated calomel electrode, SCE) was evidenced for the sample co-doped with N, S, and Fe, surpassing the activity of those with single and/or double doping. The mechanism of oxygen reduction in 0.1 M KOH was dominated by the 2e− reduction pathway at low overpotentials and shifted towards complete 4e− reduction at the most negative explored values. The presented results put forward electrochemically formed alginate gels functionalized by homogeneously dispersed multivalent cations as an excellent starting point in nanomaterial design and engineering