Galektin-3 u patogenezi gojaznosti i tip 2 Diabetes melliitus-a

Patogeneza tip 2 Diabetes mellitus-a indukovanog gojaznošću je bazirana na inflamaciji generisanoj u ekspandirajućem visceralnom adipoznom tkivu i infiltraciji makrofaga u pankreasna ostrvca. Metabolička inflamacija („metaflamacija“) je hronična inflamacija niskog stepena (engl. low-grade inflammation) indukovana brojnim štetnim metabolitima nastalim u uslovima povećanog energetskog unosa i predisponira nastanak insulinske rezistencije i tip 2 Diabetes mellitus-a. Galektin-3 je multifunkcionalni β-galaktozid-vezujući lektin eksprimiran u različitim ćelijama kako imunskog sistema, tako i ćelijama drugih tkiva i organa. U zavisnosti od svoje ćelijske lokalizacije (citoplazmatska, nuklearna, membranska ili ekstraćelijska) učestvuje u regulaciji brojnih funkcija adaptivnog i urođenog imunskog odgovora. Galektin-3 igra važnu imunoregulatornu ulogu u patogenezi autoimunskih, inflamatornih i malignih bolesti i verovatno različitim procesima regulacije metaboličke homeostaze. Glavni cilj studije je bio da ispita ulogu galektina-3 u patogenezi gojaznosti i tip 2 Diabetes mellitus-a u mišjem modelu gojaznosti indukovane primenom dijete sa visokim sadržajem masti. U studiju su uključeni miševi kojima je ciljano uklonjen gen za galektin-3 (LGALS3-/-), kao i odgovarajući galektin-3 pozitivni miševi (LGALS3+/+) soja C57BL/6. Ablacija gena za galektin-3 ubrzava nastanak gojaznosti i tip 2 Diabetes mellitus-a što se manifestuje uvećanjem telesne mase i količine visceralnog adipoznog tkiva, hiperglikemijom, hiperinsulinemijom, uvećanjem glikoziliranog hemoglobina (HbA1c), HOMA-IR (engl. homeostasis model assessment of insulin resistance) i sistemskih markera inflamacije u miševa na ishrani sa visokim sadržajem masti. U visceralnom adipoznom tkivu gojaznih LGALS3-/- miševa je povećana infiltracija tip 1 T i NKT limfocita i pro-inflamatornih M1 makrofaga, dok je zastupljenost regulatornih CD4+CD25+FoxP3+ T limfocita i alternativno aktiviranih M2 makrofaga značajno snižena u poređenju sa Galektin-3 u patogenezi gojaznosti i tip 2 Diabetes mellitus-a 178 LGALS3+/+ miševima na istoj vrsti dijete. U pankreasnim ostrvcima LGALS3-/- miševa na ishrani sa visokim sadržajem masti dokumentovana je povećana infiltracija mononuklearnih ćelija, povećana ekspresija NLRP3 inflamazoma i interleukina-1β (IL-1β) u infiltrišućim makrofagima i pojačano deponovanje metabolita AGE (engl. advanced glycation end products) i receptora za AGE (RAGE), što je praćeno povećanom ekspresijom fosforilisanog nuklearnog faktora-κB (NF-κB) r65 i aktivne kaspaze-1 u visceralnom adipoznom tkivu i pankreasnim ostrvcima. In vitro stimulacija peritonealnih makrofaga LGALS3-/- miševa lipopolisaharidom (LPS) i/ili zasićenom masnom kiselinom palmitatom indukuje pojačanu kaspaza-1 zavisnu produkciju IL-1β i fosforilaciju NF-κB r65 u poređenju sa LGALS3+/+ miševima. Isključivanje gena za NLRP3 inflamazom u peritonealnim makrofagima LGALS3-/- miševa metodom transfekcije siRNA (engl. small interfering RNA) atenuira produkciju IL-1β u odgovoru na stimulaciju palmitatom i LPS-om. Ubrzana i pojačana inflamacija u visceralnom adipoznom tkivu i pankreasnim ostrvcima galektin-3 deficijentnih miševa ukazuje na važnu protektivnu ulogu galektina-3 u gojaznosti i tip 2 Diabetes mellitus-u što bi u budućnosti moglo imati terapijske implikacije.Obesity-induced type 2 Diabetes mellitus is associated with inflammation originated in expanding visceral adipose tissue and macrophage infiltration of pancreatic islets. Metabolic inflammation, “metaflammation,” is a chronic, low-grade adipose tissue inflammation triggered by various metabolic “danger” signals during obesity that precedes the development of insulin resistance and type 2 Diabetes mellitus. Galectin-3 is a multifunctional β-galactoside–binding lectin expressed by a variety of cell types. Depending on it's cellular localization (cytoplasmic, nuclear, membrane-bound or extracellular), Galectin-3 regulates various T-cell functions and innate immune responses. Galectin-3 plays an important immunoregulatory role in pathogenesis of autoimmune, inflammatory and malignant diseases, but also in metabolic abnormalities. The aim of this study was to investigate the role of Galectin-3 in high-fat diet (HFD)– induced obesity and associated metabolic abnormalities by using mice lacking galectin-3 (LGALS3-/-) on a C57BL/6 background. Ablation of galectin-3 accelerates high-fat diet–induced obesity and diabetes. Obese LGALS3-/- mice have increased body weight, amount of total visceral adipose tissue, fasting blood glucose and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and markers of systemic inflammation compared with diet-matched wild-type (LGALS3+/+) animals. Visceral adipose tissue of obese LGALS3-/- mice exhibited increased incidence of type 1 T and NKT lymphocytes and proinflammatory М1 macrophages and decreased CD4+CD25+FoxP3+ regulatory T cells and M2 macrophages. Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and interleukin-1β (IL-1β) in macrophages, and increased accumulation of advanced glycation end products (AGEs) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3-/- animals accompanied with elevated phosphorylated nuclear factor-kB (NF-kB) p65 and mature caspase-1 protein expression in pancreatic tissue and visceral adipose tissue. In vitro stimulation of LGALS3-/- peritoneal macrophages with lipopolysaccharide Галектин-3 у патогенези гојазности и тип 2 Diabetes mellitus-а 183 (LPS) and saturated fatty acid palmitate caused increased caspase-1–dependent IL-1β production and increased phosphorylation of NF-kB p65 compared with LGALS3+/+ cells. Transfection of LGALS3-/- macrophages with NLRP3 small interfering RNA attenuated IL-1β production in response to palmitate and LPS plus palmitate. Collectively, the amplified obesity-induced inflammation in adipose tissue and pancreatic islets in LGALS3-/- mice suggest a protective role for Gal-3 in obesity and type 2 diabetes, which could be of therapeutic relevance

Wear Behaviour of Hard Cr Coatings for Cold Forming Tools Under Dry Sliding Conditions

Cr hard coatings are largely used in industry in metal cutting and cold forming processes; This work on quantitative way represents improvement, in terms of wear resistance, which is obtained by depositing Cr hard coating on foundation material. Wear testing is done on tribometer with block –on –disc contact geometry at sliding contact of Cr hard coated sample with steel disc. Testing was performed in conditions without lubrication at variable value of contact parameters (normal load, sliding speed). Cr hard coatings in all contact conditions show smaller values of wear rate

Female entrepreneurship in Serbia in the course of transition

Predmet i cilj disertacije je da prikupi ĉinjeniĉnu graĊu koja dokazuje da je ţensko preduzetništvofaktor ekonomskog razvoja i da je nacionalna ekonomija bogatija ukoliko ţene imaju ravnopravan pristup resursima, zapošljavanju i biznisu. Fokus disertacije je na samozapošljavanju kao najrasprostranjenijem obliku ţenskog preduzetništva posebno u zemljama u tranziciji. Uporedna analiza trendova u ţenskom preduzetništvu obuhvata trendove u Evropi, zemljama u razvoju, regionu Zapadnog Balkana i Istoĉne Evrope, a zatim i primer Srbije, koji ukljuĉuje i primarno empirijsko istraţivanje. Rezultat uporedne analize pokazuje da je ţensko preduzetništvo u zemljama u tranziciji preduzetništvo nuţde dok je u evropskim zemljama ono preteţno podstaknuto traganjem za novim poslovnim izazovima i šansama. TakoĊe, u zemljama u regionu, ovo preduzetništvo gotovo u istoj meri ima odlike kako socijalne kategorije tako i ekonomske, razvojne. Ekonomije u tranziciji su u većoj meri opterećene nezaposlenošću, javnim dugom, nedovoljnom konkuretnošću, što u velikoj meri objašnjava ĉinjenicu da u ovim društvima ranjive kategorije stanovništva inkliniraju preduzetništvu kao poslednjoj šansi da se samozaposle. U Srbiji, socijalnoj dimenziji doprinosi još i ĉinjenica da ne postoji sistemska podrška ţenskom preduzetništvu i da ako postoji, ona je uglavnom vezana za subvencije za samozapošljavanje i u funkciji je aktivnih mera na trţištu rada, ĉiji je cilj smanjenje opšte stope nezaposlenosti a posebno nezaposlenosti ţena, ĉiji je udeo u nezaposlenom stanovništvu veći u odnosu na muškarce. U Srbiji je zanimljivo je da je primetan stalni trend smanjivanja jaza u stopama nezaposlenosti ţena i muškaraca, koji se dodatno ubrzao od poĉetka ekonomske krize (Arandarenko, 2011).The subject and aim of the thesis is to collect material with facts proving that women entrepreneurship is a factor of economic development and that national economy is wealthier if women have equal access to resources, employment and business. The thesis is focused on self-employment as the widespread form of women entrepreneurship, especially in transition countries. The comparative analysis of trends in women entrepreneurship encompasses trends in Europe, developing countries, regions of the West Balkans and Eastern Europe, as well as the example of Serbia, which includes the primary empirical research. The result of the comparative analysis shows that women entrepreneurship in transition countries is entrepreneurship of need, while in the European countries it is for the most part stimulated by quest for new business challenges and chances. Also, in the countries in the region, this type of entrepreneurship almost to the same extent has features of both social category and economic, developmental one. Economies in transition are to a greater extent burdened by unemployment, public debt, insufficient competitiveness, which greatly explains the fact that in these societies vulnerable categories of population incline to entrepreneurship as the last chance to get self-employed. In Serbia, to the social dimension is also contributing the fact that there is no system support to women entrepreneurship; and even if it exists, it is mainly related to subsidies for self-employment and serves as active measures at the labour market, aiming at reduction of general unemployment rate, in particular women unemployment, whose share in the unemployed population is higher than men‟s

Tribological Potential of Hybrid Composites Based on Zinc and Aluminium Alloys Reinforced with SiC and Graphite Particles

The paper reviews contemporary research in the area of hybrid composites based on zinc and aluminium alloys reinforced with SiC and graphite particles. Metal matrix composites (MMCs) based on ZA matrix are being increasingly applied as light-weight and wear resistant materials. Aluminium matrix composites with multiple reinforcements (hybrid AMCs)are finding increased applications because of improved mechanical and tribological properties and hence are better substitutes for single reinforced composites. The results of research show that the hybrid composites possess higher hardness, higher tensile strength, better wear resistance and lower coefficient of friction when compared to pure alloys

Tribological behaviour of a356/sic nanocomposite

The paper presents tribological behaviour of aluminium nanocomposite A356/SiC produced by the compocasting process with mechanical alloying preprocessing (ball milling). Tribological tests were performed on tribometer with block-on-disc contact geometry under lubricated sliding conditions. Influence of amount of silicon carbide reinforcement (0, 0.2, 0.3 and 0.5 wt.%) on wear rate was investigated in the following testing conditions: sliding speed of 0.25 and 1.0 m/s, normal load of 40 N and 100 N and at sliding distance of 1000 m. Analysis of worn surface of nanocomposites was performed by using SEM equipped with EDS

Tribological behaviour of a356/sic nanocomposite

The paper presents tribological behaviour of aluminium nanocomposite A356/SiC produced by the compocasting process with mechanical alloying preprocessing (ball milling). Tribological tests were performed on tribometer with block-on-disc contact geometry under lubricated sliding conditions. Influence of amount of silicon carbide reinforcement (0, 0.2, 0.3 and 0.5 wt.%) on wear rate was investigated in the following testing conditions: sliding speed of 0.25 and 1.0 m/s, normal load of 40 N and 100 N and at sliding distance of 1000 m. Analysis of worn surface of nanocomposites was performed by using SEM equipped with EDS

ELECTROCHEMICAL BEHAVIOR AND DIFFERENTIAL PULSE VOLTAMMETRIC DETREMINATION OF CEFTAZIDIME, CEFUROXIME-AXETIL AND CEFTRIAXONE

The voltammetric behavior of ceftazidime, cefuroxime-axetil and ceftriaxone has been examined in pH range 2.0-8.0 by cyclic and differential pulse voltammetry using hanging mercury drop electrode. The effect of the pH and scan rate on the peak currents and potentials was examined. The nature of the electrode reduction process in acid solution was found to be diffusion controlled for ceftazidime and cefuroxime-axetil, but strongly influenced by the adsorption in the case of ceftriaxone reduction. Ceftriaxone adsorption decreased with the increase of pH, and at pH>7 the reduction process became diffusion controlled. Based on this study, DPV method was developed, validated and suggested for determination of ceftazidime at pH 2.0, cefuroxime-axetil at pH 3.5 and for ceftriaxone at pH 8.0. Linear concentration ranges, LOD and LOQ were determined. The method was applied for determination of cephalosporins in pharmaceutical dosage forms: Ceftazidime powder, Ceroxim tablets and Longaceph powder for injection solution

POTENTIAL OF CHAMPIGNONS CULTIVATED ON DIGESTED ORGANIC WASTE IN THE PREVENTION AGAINST OXIDATIVE STRESS AND NEURAL DAMAGE

Agaricus bisporus also known as champignon or white button mushroom was cultivated on digested organic waste. Its aqueous extract was investigated for the antioxidant potential, which could strengthen the protection of organism against oxidative stress damages. Likewise, acetylcholinesterase (AChE) inhibitory activity was observed. The crucial role of AChE in neural transmission makes it a primary target of a large number of cholinesterase-inhibiting drugs involved in the prevention of neurodegenerative diseases e.g. Alzheimer’s disease (AD). The antioxidant activities were evaluated by in vitro models including, 1,1-diphenyl-2- picrylhydrazyl (DPPH) free radical scavenging activity, prevention of lipid peroxidation (LPx) in a linoleic acid model system and chelating ability on ferrous ions. Based on the analysis, hot water extracts showed a typical carbohydrate pattern with the presence of polyphenols and small amounts of proteins. With regard to scavenging ability on DPPH radicals, the EC50 value for A. bisporus was 0.89 mg/ml, the EC50 value of the chelating abilities on ferrous ions was 1.38 mg/ml and for inhibition of LPx EC50 value was found to be 1.77 mg/ml. Extract of A. bisporus had a noticeable inhibition towards AChE, IC50=1.02 mg/ml and exerted weak toxicity against healthy human peripheral blood mononuclear cells (PBMC). More than 60% of cell viability was observed at 2 mg/ml. The good antioxidative properties and AChE inhibitory activity of A. bisporus aqueous extract make it suitable for everyday use as an inexpensive dietary supplement

Nanoindentation of Za-27 Alloy Based Nanocomposites Reinforced with Al2O3 Particles

Nanoindentation has been widely used for material mechanical characterization. In this study, nanocompozite of ZA-27 alloy matrix reinforced with different volume fractions of nanometric Al2O3 ceramic particles ranging from 0 to 5 %, were produces using compocasting technique. Nanoindentation tests were performed using Berkovich three sided diamond pyramid, with maximum load of 100 mN and maximum load holding time of 15 s. Indentation imprints were investigated using optical and atomic force microscopy (AFM). Average particle size was 20-30 nm. Nanoindentation tests showed that nanocomposites have higher values of hardness and lower values of elastic modulus in comparison to the ZA-27 matrix alloy. Obtained results have different values in comparison to the theoretical investigations

Biohidrogelovi poli(metakrilne kiseline): bubrenje i kontrolisano otpuštanje kofeina

Modern society are faced with lot of challenges in the treatment of many diseases, especiallywith serious ones such as cancer. Safer and more efficient treatment of the cancer patients are maingoals which researchers are aiming. One of the good approaches can be drug delivery systems.Still, a lot of anticancer drugs are poorly water-soluble and their encapsulation and controlled releasecan be quite challenging. Present study is focused to improve drug delivery system based onhydrophilic poly(methacrylic acid) and amphiphilic casein with encapsulated poorly water-solublecaffeine, which has been developed through our previous research. The hydrogels with 1.6mol% ofcrosslinker and 100% of neutralization degree of methacrylic acid are synthetized (PMAC-100N-4M). The swelling process of the PMAC-100N-4M hydrogels and caffeine release are analyzed intwo environments which simulate human stomach and intestines. It is also investigated how thechange in the encapsulated caffeine weight and the addition of liposomes with encapsulated caffeine,affect swelling degree of the PMAC-100N-4M hydrogels and release of caffeine. The resultsshow that controlled release of caffeine is improved, therefore overall therapy can be enhanced.Savremeno društvo je suočeno sa mnogim izazovima u tretamanu raznih bolesti, naročito ozbiljnih oboljenja kao što je rak. Glavni ciljevi naučnika su da se postigne bezbednija i efikasnija terapija pacijenata koji se leče od raka. Jedan od dobrih načina da se to postigne su sistemi za dostavu lekova. Ipak, mnogi antikancerogeni lekovi su slabovodorastvorni, pa bi veliki izazov mogao da bude inakpsulacija i njihovo kontorlisano otpuštanje iz sistema za dostavu lekova. Cilj ovog rada je da se unapredi sistem za dostavu lekova na bazi hidrofilne poli(metakrilne kiseline) i amfifilnog kazeina sa inkapsuliarnim slabo vodorastvornim kofeinom, koji je razvijen tokom našeg prethodnog istraživanja. U ovom radu sintetisani su hidrogelovi sa 1,6mol% umreživača i 100% neutralisanom metakrilnom kiselinom (PMAC-100N-4M). Procesi bubrenja PMAC-100N-4M hidrogelova i kontrolisanog otpuštanja kofeina su ispitivani u dve sredine koje simuliraju želudac i tanko crevo čoveka. Takođe je ispitano kako promena količine inkapsuliranog kofeina i dodatak lipozomne suspenzije sa inkapsuliranim kofeinom utiče na procese bubrenja PMAC-100N-4M hidorgelova i otpuštanje kofeina. Rezultati pokazuju da je proces kontrolisanog otpuštanje kofeina unapređen, a samim tim je moguće unaprediti i celokupnu terapiju