The metabolic features of tumor-associated macrophages : opportunities for immunotherapy?

Funding: This work was supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia.Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.Publisher PDFPeer reviewe

Uloga pH vrednosti u muškom i ženskom reproduktivnom traktu svinja

For a long time, in practice, and science, has been known that pH values of sperm and vagina are important for successful fertilization. In this investigation this fact was confirmed, and the goal was to investigate the role of pH values through whole reproductive tract of male and female individuals: testis, rete testis, epididymis, ductus deferens, Cowper's gland, vesicula seminalis, prostata, corpus cavernosus, corpus spongiosus, epitel tissue of penis tube, sperm, vagina, uterus, horn of uterus, oviduct, fimbrie ovarica, ovarium, follicular fluid. Measurement was performed in reproductive active males as well as before and after ovulation in females. Porcine reproductive tracts (per 15 female and male individuals) were collected from institute's slaughterhouse, immediately post mortem dissected, homogenised and pH values were measured (according to method Rede&Rahelić (1969)). Ovarium and follicular liquid have the highest pH values (7,4) in females, but a small peak in preovulatory oviduct is also present and corresponded to pH of sperm of reproductive fully active male individuals (pH=app.7,2). After fertilization pH in surrounding of zygot (through depolarisation of its membrane) in oviduct, and zygot which then has external decreased pH value moves to less pH values regions by the same principle, that means to uterus, (pH between 7,2 (horn) and 7,07(cervix)) in postovulatory female reproductive tract, where nidation of blastocyst occurs. This investigation could help to elucidate knowledge about reproductive physiology in vivo, giving importance to role of pH values along reproductive tract of male and female individuals.U praksi i nauci je odavno poznato da je pH vrednost sperme i vagine od značaja za uspešnu oplodnju. U ovom istraživanju je to potvrđeno, a cilj istraživanja je bio da se ispita uloga pH vrednosti duž celog polnog trakta mužjaka i ženki svinja: od testisa, epididimisa ductus deferens, Kauperove žlezde, semene kesice, prostate, corpus cavernosus i corpus spongiosus penisa, epitelnog tkiva cevi penisa, sperme vagine, materice, rogova materice, jajovoda, fimbrie ovarica, jajnika, do folikularne tečnosti jajnika. Merenje je izvršeno kod polno aktivnih mužjaka i ženki (pre- i postovulatorno). Polni trakt svinja (po 15 ženskih i muških jedinki) je uzet iz eksperimentalne klanice instituta, odmah post mortem izvršena je disekcija, homogenizacija čvrstih tkiva i merene su pH vrednosti (prema metodi Rede i Rahelić (1969)). Jajnik i folikularna tečnost jajnika imale su najvišu pH vrednost od 7,4, dok je mali ali značajan porast pH vrednosti u preovulatornom jajniku odgovarao pH vrednosti sperme polno aktivnih mužjaka (pH oko7,2). Nakon oplodnje u okolini zigota (putem depolarizacije membrane) u jajovodu se snižava pH vrednost, što ostaje za dalja istraživanja, i zigot koji tada ima spoljašnju smanjenu pH, kreće se, potpomognut pokretima trepljastog epitela, ka regionu niže pH vrednosti, odnosno materici (u rasponu pH od 7,2 u rogu materice do 7, 07 u cerviksu) u postovulatornom polnom traktu ženki i u materici se odvija nidacija odnosno ugnježđivanje blastule ukoliko je oplodnja uspešna. Ova istraživanja bi mogla da rasvetle znanja o polnoj fiziologiji in vivo, dajući značaj pH vrednostima duž polnog trakta muških i ženskih jedinki

Misterios de la vida de Jesucristo en la puerta de madera de la catedral de Split

La catedral de Split es, de hecho, el ex mausoleo del emperador Diocleciano, transformado en Iglesia. La catedral fue enriquecida durante el siglo xiii con varias obras escultóricas románicas de gran maestría. Entre ellas destacan la puerta de madera de doble batiente con escenas que representan los misterios de la vida de Cristo, esculpidas como bajorrelieves por el artista Andrija Buvina, natural de Split, inaugurada el 23 de abril del 1214. Entre las pocas puertas de madera medievales que conservamos es la única que se encuentra aún in situ y en un buen estado de conservación. Sobre cada una de las hojas de la puerta se encuentran siete pares de escenas en bajorrelieve que representan la vida, la muerte y la gloria de Cristo Redentor. Esta puerta está considerada, con razón, como una obra maestra de la escultura medieval en Croacia. La clave iconológica de la obra de Buvina consiste en la mistagogia cristológica y soteriológica de las escenas de la vida del Salvador. ---------------- Split Cathedral is the former mausoleum of the Emperor Diocletian which was transformed into a church. The Cathedral was embellished in the 13th century with several magnificent Romanesque sculptures. Outstanding among these is the double wooden door decorated with scenes representing the life of Christ, carved as a bas-relief by Andrija Buvina, a native of Split, which was inaugurated on 23 April 1214. Of the few medieval wooden doors that are still preserved, this is the only example that is still in its original position and in a good state of conservation. Both of the doors contain seven pairs of scenes in basrelief representing the life, death and glory of Christ the Redeemer. This door is rightly regarded as a master work of medieval sculpture in Croatia. The iconological key to Buvina’s work lies in the Christological mystagogy and soteriology of the life our Our Lord

Uticaj genotipa na randman i sadržaj tkiva u junećim trupovima

Differences in dressing percentage and content of different tissues in carcasses of Domestic Spotted breed and crosses F1 generation with Charolais and Limousine breed were investigated. Total of 30 carcass sides were dissected, 10 in each genetic group. Genotype exhibited very significant effect (p lt 0,01) on dressing percentage and content of tissues, except for connective tissue. The highest dressing percentage was determined in crosses with Charolais (59,92%) followed by crosses with Limousine (59,85%), with statistically significant difference (p lt 0,01) to dressing percentage established for heads of domestic Simmental breed (55,71%). Crosses with Charolais and Limousine realized considerably higher content of muscle tissue (81,5% and 80,7%) compared to heads of domestic Simmental breed (77,86%). Content of bone tissue of 16,45% in carcasses of domestic Simmental breed was considerably higher (p lt 0,01) compared to both groups of crosses, whereas the content of fat and connective tissue was considerably higher (p lt 0,05) only in relation to crosses with Limousine.Proučavane su razlike u randmanu i sadržaju tkiva u trupovima između domaće simentalske rase i njenih meleza F1 generacije sa šarole i limuzin rasom. Ukupno je disecirano 30 polutki, po 10 u svakoj genotipskoj grupi. Genotip je ispoljio vrlo značajan uticaj (p lt 0,01) na randman i sadržaj tkiva, izuzev udela vezivnog tkiva. Najveći randman utvrđen je kod meleza sa šaroleom (59,92%) pa limuzinom (59,85%), uz statistički značajnu razliku limuzina i šarolea ostvarili su značajno veći sadržaj mišićnog tkiva (81,5% i 80,7%) u odnosu na grla domaće simentalske rase (77,86%). Sadržaj koštanog tkiva od 16,45% u trupovima domaće simentalske rase bio je značajno veći (p lt 0,01) u odnosu na obe grupe meleza, dok je sadržaj masnog i vezivnog tkiva bio značajno veći (p lt 0,05) samo u odnosu na meleze limuzina

Naftenske kiseline - alternativni stimulatori ožiljavanja kod mikroizbojaka bagrema

The study describes the rooting effect of naphthenates and their fractions on in vitro grown Robinia pseudoacacia L. shoots. Natural naphthenic acids have been isolated by alkaline extraction from middle fraction of crude oil type “Velebit” from Vojvodina, characterized and fractionated. Black locust shoot bases were immersed in ACM medium [Ahuja, 1984] without agar supplemented with either 10, 50 or 100 µM of basic naphthenate preparation, naphthenate fractions obtained by extraction at different pHs (pH 2, pH 4, pH 7 and pH 9), or indole3-butyric acid (IBA). Treated shoots have been then grown on hormone-free medium for four weeks. Significant differences among test treatments were recorded during the third and the fourth week of in vitro cultivation. Final evaluation was performed on the basis of rooting percentage after four weeks of cultivation. The highest rooting percentage (>70%) was achieved after the treatment with solution containing 50 µM of IBA. However, treatment with 10 µM of naphthenate preparation achieved also positive effect on rooting (>60%). Average rooting percentage in the control treatment was just 45%. Our results with black locust confirm previous results gained with some other agricultural and forest tree species that naphthenates have the potential to stimulate rooting in shoots and cuttings.Rad opisuje efekat naftenata na ožiljavanje mikroizbojaka bagrema in vitro. Naftenske kiseline su izolovane baznom ekstrakcijom iz srednje frakcije sirove nafte tipa “Velebit”, koja je opisana u ranijim radovima. Donji deo mikroizbojka je uronjen jedan minut u tečni ACM medijum [Ahuja, 1984] u koji je dodato 10, 50 ili 100 µM osnovne mešavine natrijum-naftenata ili njenih pojedinih frakcija dobijenih ekstrakcijom na različitim pH (pH 2, pH 4, pH 7 ili pH 9), odnosno 10, 50, 100 µM ili 1g/l indol-3-buterne kiseline (IBA). Kontrolni tretman je činio ACM medijum bez ispitivanih aktivnih materija. Tretirani mikroizbojci su zatim gajeni na čvrstoj ACM podlozi bez hormona. Značajne razlike među ispitivanim tretmanima su zabeležene tokom treće i četvrte nedelje uzgoja u in vitro uslovima. Konačna ocena je izvedena na osnovu procenta ožiljavanja nakon četiri nedelje uzgoja. Najviši procenat ožiljavanja je postignut rastvorom sa 10 µM natrijum naftenata, nakon čega je ostvaren značajan pozitivan efekat na procenat ožiljavanja (>60%) u odnosu na kontrolni tretman (oko 45%). Rezultati do kojih smo došli kod bagrema potvrđuju ranije rezultate koji su dobijeni kod poljoprivrednih i šumskih drvenastih vrsta o mogućnosti stimulacije ožiljavanja mikroizbojaka i reznica solima naftenskih kiselina