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The role of circadian clock genes in breast cancer
No full textCirkadijalni ritmovi su dnevne oscilacije u metaboličkim, psihološkim i fiziološkim procesima u većini organizama. Deregulacija ovih ritmova povezana je s brojnim patološkim stanjima, uključujući depresiju, dijabetes, metabolički sindrom i rak. Jedno od takvih stanja je i rak dojke. Globalni utjecaj raka dojke je sve veći. Rizik za nastanak raka dojke 5 puta je veći u razvijenim zemljama nego u nerazvijenim. Jasno je da moderan način života utječe na poremećaje u cirkadijalnom sustavu i samim time na nastanak raka dojke. Ovaj rad sveobuhvatno analizira najnovije podatke iz literature o ulozi satnih gena u razvoju te vrste raka s naglaskom na analizu ekspresije i metilacije navedenih gena u tumorskom tkivu, te na utjecaj melatonina kao glavnog izlaznog faktora cirkadijalnog ritma na nastanak i proliferaciju raka dojke. Glavna otkrića ispitivanja na ljudima ukazuju na to da je ekspresija cirkadijalnih gena deregulirana u raku dojke. Uočena je smanjena ekspresija PER, CRY i CLOCK gena, dok je ekspresija TIMELLESS gena često povišena što je povezano sa lošijom prognozom bolesti. Poremećaj u ekspresiji ovih gena može ali i ne mora biti povezana sa njihovom metilacijom. Potrebna su daljnja istraživanja o ulozi cirkadijalnih gena u patogenezi raka dojke kako bi se upotpunile dosadašnje spoznaje i pomoglo u boljem razumijevanju molekularne pozadine procesa koji dovode do karcinogeneze.Circadian rhythms are daily oscillations in metabolic, psychological and physiological processes in all living organisms. Deregulation of these rhythms is associated with a number of pathological conditions including depression, diabetes, metabolic syndrome and cancer. One such condition is breast cancer. The global impact of breast cancer is large and growing. The risk of breast cancer is 5 times higher in developed countries than in underdeveloped once. It is clear that the modern lifestyle influences the disorders of the circadian system and thus the occurrence of breast cancer. This thesis, comprehensively analyses current literature data on the involvement of circadian clock components in breast cancer development. Emphasis is on the analysis of clock gene expression and methylation in tumor tissue as well as on the influence of melatonin as a major circulating rhythm output factor on the onset and progression of breast cancer. Major findings from human studies indicate that circadian gene expression is deregulated in breast cancer. Decreased expression of PER, CRY and CLOCK genes has been observed, while TIMELLESS gene expression is often elevated, which is associated with poorer disease prognosis. Disruption of the expression of these genes might be related to their methylation. Further investigation on the role of circadian genes in the pathogenesis of breast cancer is required to complement current knowledge and for better understanding of the molecular mechanisms, underlying processes leading to carcinogenesis
Adsorption testing of olives leaves extract on zeolite carriers
Get PDFLišće masline jedan je od nusprodukata proizvodnje maslinovog ulja te iako
je njegov potencijal prepoznat nije dovoljno iskorišten. Istraživanja su
dokazala da je lišće masline bogat izvor fenolnih spojeva od kojih je
najzastupljenija komponenta oleuropein. Oleuropein kao i ostale fenolne
komponente identificirane i opisane u ovom radu pokazuju antioksidativne,
antiinflamatorne, kardioprotektivne i neuroprotektivne učinke. Kao takav
ekstrakt lišća masline već se koristi kao dodatak prehrani u svrhu
poboljšanja ljudskog zdravlja.
Zeoliti se zbog svojih adsorptivnih sposobnosti prvenstveno koriste u
uklanjanju raznih nečistoća no pokazao kao dobar nosač lijekova. Ukoliko
bi na zeolit vezali spojeve korisne za zdravlje ljudi kao što su primjerice
fenoli iz lišća masline dobio bi se dodatak prehrani s jakim antioksidativnim
sposobnostima.
Različiti zeoliti pokazuju različitu adsorptivnu sposobnost za određene
spojeve. Stoga je promatrana promjena u fenolnom sastavu ekstrakta lišća
masline nakon dodatka četiri različita zeolita (zeolit A, TMAZ, PMA, PMA-O2)
UHPLC metodom s detektorom s nizom dioda. Primjećeno je da se
koncentracije oleuropeina, 3-hidroksitirosola i pinorezinola smanjuju za sve
zeolite, što nije slučaj za tirosol, 3-p-kumarinsku kiselinu i phidroksifenilocetnu kiselinu za sve navedene zeolite. Od zeolita najveće
smanjenje koncentracije 6 ispitivanih fenola primjećeno je dodatkom PMA
zeolita.Olive leaves are one of the byproducts of olive oil production and although
its potential is recognized, it is not sufficiently exploited. Studies have shown
that olive leaves are rich in phenolic compounds, most of which is the
oleuropein component. Oleuropein as well as other phenolic components
identified and described in this paper exerts antioxidative,
antiinflammatory, cardioprotective and neuroprotective effects. As such,
olive leaf extract is already used as a dietary supplement for the purpose of
improving human health.
Because of their adsorptive abilities, zeolites are primarily used in removing
various impurities, but in addition they have proven to be a good carrier for
drugs. If zeolite binds compounds useful for human health such as phenols
from olive leaves we would achieve a nutrition supplement with strong
antioxidant capabilities.
Various zeolites exhibit different adsorptive abilities for certain compounds.
Therefore, a change in the phenolic composition of the olive leaves after
adding four different zeolites (zeolite A, TMAZ, PMA, PMA-O2) was observed
with UHPLC method with a diode array detector. It has been noted that the
concentrations of oleuropein, 3-hydroxythyrosol and pinorezinol are
reduced for all zeolites, which is not the case for thyrosol, 3-p-coumaric
acid and p-hydroxyphenylacetic acid for all the zeolites mentioned. The
highest decrese in the concentration of 6 phenols investigated was observed
by the addition of PMA zeolite
Robertsonove translokacije i neplodnost čovjeka
No full textNeplodnost je stanje u kojem je, kod seksualno aktivnih parova uz redovite nezaštićene spolne odnose, prisutan izostanak trudnoće unutar godinu dana. Danas je stanje neplodnosti prisutno u više od 186 milijuna ljudi diljem svijeta, a s porastom ove brojke neplodnost predstavlja sve veći zdravstveni problem. Mnogi faktori, kako genetski tako i okolišni, utječu na razvoj ovog stanja, a jedan od češćih uzroka je i prisutnost Robertsonovih translokacija. Robertsonove translokacije vrsta su kromosomskog preuređivanja kod kojeg dolazi do loma na dva od ukupno deset akrocentričnih kromosoma nakon čega se dugi krakovi tih kromosoma spajaju. Takva preuređivanja kromosoma proučavaju se citogenetskim metodama koje omogućuju uvid u ponašanje kromosoma tijekom mejoze i formiranje normalnih, balansiranih ili nebalansiranih gameta. U slučaju balansiranih nositelja Robertsonove translokacije koji su fenotipski normalni, javlja se problem prilikom želje za uspješnim postizanjem trudnoće. Poznavanje najnovijih platformi koje se koriste u preimplantacijskom genetskom testiranju translokacija pomaže prilikom savjetovanja takvih pacijenata i omogućava odabir adekvatnog pristupa liječenju kako bi se smanjila stopa neuspješnih trudnoća, pobačaja i rođenja djece s abnormalnostima.Infertility is a condition in which sexually active couples who practice unprotected intercourse, cannot achieve pregnancy within one year. Today, the infertility is present in more than 186 million people around the world, and it is an increasing health problem. Many factors, both genetic and environmental, affect the development of this condition, and one of the cases is the presence of Robertsonian translocations. Robertsonian translocations are a type of chromosomal rearrangements where two of the ten acrocentric chromosomes because breakage are losing mall arms, after which the long arms of these chromosomes are fused together. Such chromosomal reconstructions are studied by cytogenetic methods that allow insight into the chromosome behaviour during meiosis and the formation of normal, balanced or unbalanced gamete. In the case of balanced Robertson translocation carriers are phenotypically normal, but there is a problem with the desired successful achievement of pregnancy. Knowledge of the latest platforms used in preimplantation genetic testing for translocations helps these individuals during counselling and allows them to choose an adequate approach for treatment with the goals to reduce the rate of unsuccessful pregnancies, abortions and births of abnormal children
Tyrosine kinase inhibitors in cancer therapy
Get PDFTirozin kinaze su vrlo važna skupina enzima koji sudjeluju u procesu prijenosa signala u stanici, reguliraju rast stanica, diferencijaciju apoptozu te niz drugih biokemijskih procesa. Pretjerana ekspresija tirozin kinaza dovodi do poremećaja stanične proliferacije, te je povezana s invazijom tumora, metastazama i angiogenezom. Do danas je istražen veći broj kinaza kao meta u probiru anti-tumorskih lijekova. Inhibitori ovih enzima se natječu sa ATP za ATP vezno mjesto, čime je značajno smanjena fosforilacija tirozin kinaza, što u konačnici rezultirainhibicijom proliferacije stanica raka. Veliki je napredak u liječenju raka postignut upravo primjenom inhibitora tirozin kinaza. U ovome je radu opisana uloga tirozin kinaza u biologiji tumora, zatim navedeni su primjeri klinički odobrenih inhibitora tirozin kinaza u liječenju raka, te su predstavljeni izazovi i ograničenja u razvoju i primjeni inhibitora tirozin kinaza.Tyrosine kinases are very important group of enzymes which regulate signalling pathways in the cell that control, cell growth, differentiation, apoptosis and large number of other biochemical processes. Overexpression of tyrosine kinases leads to abnormal cell proliferation and is associated with tumour invasion, metastasis and angiogenesis. A lot of tyrosine kinases have been used as targets in the screening for anti-tumour drugs. The inhibitors of these enzymes compete with ATP for the ATP-binding site, thereby significantly reducing phosphorylation of tyrosine kinases resulting in inhibition of, cancer cell proliferation. Great progress has been made recently in cancer treatment with tyrosine kinase inhibitors. This thesis describes the role of tyrosine kinases in cancer biology, gives examples of clinically approved, tyrosine kinase inhibitors as anti-cancer drugs and discusses, challenges and limitations of tyrosine kinase inhibitors in cancer treatment
Uloga B stanica u patogenezi i terapiji multiple skleroze
No full textMultiple sclerosis (MS) is an autoimmune disorder that targets myelin sheaths in the central nervous system. It is a chronic disorder and although the axonal damage is initially reversible, at later stages it eventually results in neuroaxonal loss. It has a wide range of symptoms including sensory, autonomic nervous system, motoric and cognitive problems. It affects over 2.5 million people in the world, and starts in most patients at 20 to 40 years of age. MS is a multifactorial disease, with both genetic and environmental factors playing a role in its pathogenesis. Based on its clinical course it is categorized into four types: relapse-remitting, secondary progressive, primary progressive, and progressive relapsing MS. There is still no definite cure for MS, and all current therapies work solely by alleviating symptoms and the severity of the disease. The immune system plays a key role in MS. Autoreactive CD4+ T cells in the periphery are accepted as the most likely cause of the disease, although the triggering mechanisms for their activation are still unclear. Microglia and macrophages have both pro- and antiinflammatory effects in MS, whereas the natural killer cells have been shown to have a regulatory role and could suppress the autoreactive CD4+ T cells. B cells have been extensively studied in MS in recent years, and were found to play an important role in its pathogenesis and course, thus presenting an attractive therapeutic target. Oligoclonal immunoglobulin bands in the cerebrospinal fluid are produced by B cells and are found in over 95% of MS patients. B cells also act as antigen-presenting cells to T cells, and secrete cytokines which can be either pro-inflammatory or anti-inflammatory. In this thesis we will elaborate on the pathogenesis of MS and review MS therapies, all of which target the immune system. Specifically, we will list and compare the traditional therapies such as interferon-β and glatiramer acetate, which are still the first-line therapy for MS, with second- and third-line therapies that include various B cell-targeting approaches. With a higher efficacy than older therapies and a smaller risk of serious side effects, B cell-focused therapies are proving to be the future of MS treatmentMultipla skleroza (MS) je kronični autoimuni poremećaj koji pogađa mijelinske ovojnice u središnjem živčanom sustavu. U ranijim stadijima aksonalna šteta je reverzibilna, ali u kasnijima dolazi do neuroaksonalnog gubitka. Ima širok spektar simptoma uključujući probleme u senzornom, autonomnom živčanom i motoričkom sustavu, kao i kognitivne poteškoće. Više od 2,5 milijuna ljudi u svijetu boluje od ove bolesti, a u većine pacijenata započinje u dobi od 20 do 40 godina. MS je multifaktorijalna bolest u čijoj patogenezi ulogu imaju i okolišni i genetski faktori. Na temelju kliničkog tijeka, MS je kategorizirana u četiri tipa: relapsno-remitirajuća, sekundarno progresivna, primarno progresivna i progresivno relapsirajuća. Još uvijek ne postoji definitivni lijek za MS i sve trenutno dostupne terapije samo umanjuju simptome. Imuni sustav igra ključnu ulogu u ovoj bolesti. Autoreaktivne CD4+ T stanice na periferiji su prihvaćene kao najvjerojatniji uzrok bolesti, iako mehanizmi njihove aktivacije još uvijek nisu jasni. Mikroglija i makrofagi imaju i proupalne i protuupalne učinke u MS-u. NK stanice imaju regulatornu ulogu i mogle bi utišati autoreaktivne CD4+ T stanice. Posljednih godina B stanice su opsežno istraživane i pokazalo se da igraju bitnu ulogu u patogenezi i tijeku MS-a te ih to čini dobrom terapijskom metom. B stanice proizvode oligoklonalne vrpce imuoglobulina koje se nalaze u preko 95% pacijenata. B stanice su također antigen-prezentirajuće stanice T stanicama, te proizvode citokine koji imaju ili proupalni ili protuupalni učinak. U ovom završnom radu bit će pojašnjena patogeneza MS-a i opisane terapije za MS. Sve terapije za MS djeluju na imunosni sustav. Tradicionalne terapije poput glatiramer acetata i interferona-β usporedit će se s novijim terapijama koje na neki način djeluju na B stanice. Zbog veće učinkovitosti od starijih terapija i manjeg rizika od ozbiljnih nuspojava, terapije fokusirane na B stanice su se pokazale kao budućnost tretiranja MS-a
Klasifikacija i identifikacija glijalnih stanica središnjeg živčanog sustava
Get PDFGlia is a very heterogeneous cell population comprised of very different cells that work together to maintain central nervous system (CNS) homeostasis. Long believed role of glia being the acellular connective tissue has been overturned, and they have become focus of intense research. Due to the technological advances, new functions are being discovered, as well as interactions of glia with neurons and the glia between themselves. During CNS development, radial glia guide neuronal migration, NG2 receive neuronal inputs and inhibit axonal growth, oligodendrocytes myelinate axons, astrocytes form the blood-brain-barrier (BBB) and regulate optimal conditions, such as pH, ion gradient, neurotransmitter reuptake. Moreover, ependymal cells form cerebrospinal fluid (CSF) and protect CNS, while microglia remove unwanted cells. In pathological conditions, glia interact with immune system and release neurotrophic factors. However, many issues remain to be addressed, because identification and characterization of glia still represents a challenge. Glia differ in morphology, biochemistry and functions. They are most commonly identified by expressed molecules on cell membrane, cytoskeletal proteins or signal molecules, such as growth factors, neurotrophic factors, hormones or cytokines they release. Identification presents a problem because there is an insufficient amount of markers that can specifically identify a particular glial (sub)type because the markers are often co-expressed by several cell types of the nervous system. Co-expression and heterogeneity of glial (sub)types often lead to assignment of the same category. The aim of this work is to bring together the research conducted on CNS glia and to compare different opinions and findings throughout the history, critically remarking the research. This work focuses on characterization and identification of neuroglia types and pointing out the similarities and differences among them. Most commonly used immunostaining markers, for example, GFAP, S100β, Nestin, NG2 and Iba1 are analyzed with their advantages and weaknesses regarding specificity. As the glia are vital part of CNS in both healthy and pathological conditions, more research should be directed to them. Research should also involve humans and depict unique primate glia, with still unknown functions.Glija je vrlo heterogena populacija sastavljena od vrlo različitih stanica koje zajedno sudjeluju u održavanju homeostaze središnjeg živčanog sustava (SŽS). Dugo se smatralo da se radi o acelularnom vezivnom tkivu, dok je danas to gledište u potpunosti odbačeno te je sve više istraživanja usmjereno prema glijalnim stanicama. Zahvaljujući tehnološkom napretku, otkrivaju se nove posebitosti u funkciji tih stanica te njihovoj interakciji kako s neuronima, tako i međusobno. Tijekom razvoja SŽS, radijalne glije vode migraciju neurona, NG2 stanice primaju informacije od neurona i inhibiraju aksonalni rast, oligodendrociti formiraju mijelin, astrociti formiraju krvno-moždanu barijeru (KMB) i reguliraju optimalne uvjete poput pH, ionskog gradijenta, reapsorpcije neurotransmitera. Nadalje, ependimalne stanice formiraju cerebrospinalni fluid (CSF) i štite SŽS, a mikroglija uklanjaju neželjene stanice. U patološkim uvjetima glijalne stanice djeluju s imunosnim sustavom i otpuštaju neurotrofičke faktore. Međutim, mnogo još preostaje neobjašnjeno, a već i sama identifikacija i karakterizacija glija predstavljaju izazov. Glijalne stanice se razlikuju po morfologiji, biokemiji i funkcijama. Za njihovu identifikaciju se najčešće koriste eksprimirane molekule na staničnoj membrani, proteini citoskeleta ili signalne molekule poput faktora rasta, neurotrofičkih faktora, hormona i citokina koje otpuštaju. Identifikacija nailazi na probleme jer ne postoji dovoljno markera koji mogu sa sigurnošću odrediti (pod)tipove glija zbog toga što mnoge markere ko-eksprimiraju različite stanice živčanog sustava. Ko-ekspresija i heterogenost često vodi prema svrstavanju (pod)tipova glija u istu kategoriju. Cilj ovog rada je sakupiti istraživanja provedena na glijalnim stanicama SŽS i usporediti različite stavove i pronalaske kroz povijest uz kritički osvrt. Ovaj rad se usredotočuje na karakterizaciju i identifikaciju tipova glijalnih stanica te usporedbi međusobnih sličnosti i razlika. Označavanje glijalnih stanica pomoću antitijela, kao najpopularnija metoda identifikacije je analizirana prema korištenim markerima poput GFAP, S100β, Nestin, NG2, Iba1 i sl. te su navedene njihove prednosti i nedostatci. Kako su glije ključan dio središnjeg živčanog sustava u zdravim i patološkim uvjetima, više istraživanja treba biti usmjereno prema njima. Istraživanja bi se trebala proširiti i na ljude i opisati posebne vrste glija primata, još nepoznatih funkcija
Photoredox catalysis: New tool in the synthesis of complex drug analogues
No full textSloženost strukture lijekova predstavlja velik izazov za modernu katalizu jer se modifikacijom strukture želi očuvati učinkovitost lijeka, a spriječiti razvoj nuspojava. Sve više se istražuju nove metode i reakcije koje će uz dobre prinose u reakciji, omogućiti sintezu novih kandidata lijekova s određenom biološkom aktivnosti. Fotoredoks kataliza je proces u kojem kompleksi prijelaznih metala i odgovarajući ligandi imaju sposobnost pretvorbe vidljive svjetlosti u kemijsku energiju pomoću reakcije prijenosa elektrona s organskim supstratima. Opisano je da fotoredoks kataliza posredovana vidljivom svjetlosti pospješuje stvaranje radikalnih intermedijera te na taj način omogućuje brzu i jednostavnu funkcionalizaciju u kasnoj fazi sinteze kandidata za buduće lijekove. U ovom radu fotoredoks katalizom pomoću različitih metoda i katalizatora poput iridijevih kompleksa sa različitim ligandima formirane su nove C-C veze i sintetizirane molekule koje su već opisane u literaturi, ali i nove molekule koje do sada nisu sintetizirane na taj način. Uspješno je sintetiziran skupi iridijev katalizator iz jeftinih kemikalija i opisana je njegova primjena u alkilaciji kumarina, spojeva koji su važne supstance u farmaceutskoj industriji. Tehnologije koje su korištene uključuju reakcije u konvencionalnom reaktoru pomoću snažne LED lampe (plavo vidljivo područje spektra), uređaj za tekućinsku kromatografiju UPLC-DAD-MS za praćenje napretka reakcije i NMR za analizu strukture sintetiziranih molekula. Metode fotoredoks katalize opisane u ovom radu mogu se upotrijebiti na drugim heterociklima s ciljem sinteze i modifikacije intermedijera za dobivanje kompleksnih analoga lijekova.The complexity of the drug structure poses a great challenge to modern catalysis because the modification of the structure seeks to preserve the efficacy of the drug while preventing the development of side effects. More and more new methods and reactions are being explored which, with good yields in the reaction, will allow the synthesis of new drug candidates with certain biological activity. Photoredox catalysis is a process in which transition metal complexes and corresponding ligands have the ability to convert visible light into chemical energy by electron transfer reaction with organic substrates. It has been described that visible light-mediated photoredox catalysis facilitates the formation of radical intermediates and thus enables rapid and easy late-stage functionalization of drug candidate synthesis. In this thesis, photoredox catalysis using different methods and catalysts such as iridium complexes with different ligands, has formed new C-C bonds and synthesized molecules that have already been described in the literature, but also new molecules that have not yet been synthesized that way. An expensive iridium catalyst has been successfully synthesized from inexpensive chemicals and its use in the alkylation of coumarins, compounds that are important substances in the pharmaceutical industry, has been described. The technologies used include reactions in a conventional reactor using a powerful LED lamp (blue visible spectrum), a liquid chromatography device UPLC-DAD-MS to monitor the progress of the reaction, and NMR to analyze the structure of the synthesized molecules. The photoredox catalysis methods described in this thesis can be applied on other heterocycles to synthesize and modify intermediates to obtain complex drug analogues
Triplet excited states and singlet oxygen yields of meso-substitued porphyrins
Get PDFPopularnost fotodinamičke terapije proizlazi iz citotoksičnog učinka koji se
postiže na ciljano tkivo, bez uništenja zdravog tkiva. Sastoji se od
administracije fotosenzibilne molekule, primjene svjetla odgovarajuće
valne duljine i reakcije s molekularnim kisikom. Ključan proces je prijelaz
fotosenzibilizatora u tripletno pobuđeno stanje te nastanak reaktivnog
singletnog kisika. Zbog toga, modifikacijom svojstava fotosenzibilizatora,
nastoji se pojačati efikasnost ove terapije. Traži se molekula visokih
kvantnih prinosa tripletnog pobuđenog stanja i singletnog kisika. Meta
istraživanja su većinom porfirini od kojih su posebice zanimljivi meso
supstituirani porfirini čiji supstituenti znatno mijenjaju vrijednosti
istaknutih kvantnih prinosa. S obzirom da se može utjecati na broj i vrstu
supstituenta u meso poziciji porfirinskog prstena, to je fokus velikog broja
znanstvenika. Pokazani su rezultati uvođenja elektron-donorskih i
akceptorskih skupina, silicija, halogenih elemenata, te ugljikovodičnih
lanaca različite duljine. Dao se osvrt i na pulsnu fluorescentnu tehniku te
tehniku mjerenja udjela porfirina u tripletnom pobuđenom stanju. S
obzirom da je derivat s bromom pokazao najveći prinos tripletnog
pobuđenog stanja (ΦT = 0.98), a derivat sa silicijem najveći prinos
singletnog kisika (Φ∆ = 0.77), obećavajući porfirini su oni u čijoj se meso
poziciji nalazi brom te silicij. Dao se uvid i u indirektan utjecaj
supstituenata na kvantne prinose fotofizikalnih procesa, na primjeru
ugljikovodičnih lanaca u meso poziciji. Lanac sa 22 ugljikova atoma je
hidrofoban supstituent koji povećava agregaciju porfirina u vodenom
mediju. Na taj način smanjuje njegovu učinkovitost u fotodinamičkoj
terapiji (ΦT < 0.08). Nasuprot navedenih zaključaka, rezultati koji se ne
mogu sa sigurnošću interpretirati i trebaju dodatna istraživanja su
metoksifenilna skupina i atom fluora u meso poziciji.The popularity of photodynamic therapy results from a cytotoxic effect
achieved on target tissue without destroying healthy tissue. It is based on
administration of a photosensitizer, light of the appropriate wavelength
and reaction with molecular oxygen. The key process is transition of the
photosensitizer to the triplet excited state and generation of reactive
singlet oxygen. Therefore, the goal is to enhance the efficacy of the
therapy by modifying properties of the photosensitizer. For this there is a
need for a molecule of high quantum yields of a triplet excited state and a
singlet oxygen. Target of the current research are porphyrins, of which the
most interesting are meso-substitued porphyirins. Their substituents
significantly change the value of mentioned quantum yields. Since number
and type of substituents is adjustable, this is the focus of many studies
and investigations. Here are shown the results of introduction of electrondonor and electron-acceptor groups to the porphyrin ring, as well as alkyl
chains, silylation and halogenation. Also, here is given the overview of two
techniques, pulse train fluorescence technique and measurement of the
porphyrins in triplet excited state. Since the bromine derivative showed
the highest quantum yield of triplet excited state (ΦT = 0.98) and silylated
derivative the highest quantum yield of singlet oxygen (Φ∆ = 0.77), the
promising porphyrins are the ones with bromine and silicon in the meso
position. Also, the example of alkyl chains in meso position, gives the
insight in the indirect impact of substituents on quantum yields. Alkyl
chain with 22 carbon atoms is hydrophobic and it increases the
aggregation of porphyrins in aquatic medium. In that way, the efficacy of
photosensitizer is decreased (ΦT < 0.08). As opposed to these conclusions,
results that cannot be interpreted with same certainty and need more
research are metoxyphenyl group and fluorine in meso position
Convergence of aggregating proteins involved in mental illness and neurodegenerative disorders
No full textSchizophrenia and recurrent affective disorders like depression and bipolar disorder are neuropsychiatric conditions with poorly understood background and are some of the leading causes of disability worldwide. Existing diagnostic methods for these disorders rely entirely on a subjective psychiatric evaluation. Recent searches for biological markers of the diseases have identified protein aggregation and related changes in the protein homeostasis as potential factors in development of mental illness.
Disturbed in Schizophrenia 1 (DISC1) is one of the proteins found in aggregates in the brain tissue of patients. DISC1 behaves as a scaffold protein that interacts with a variety of other proteins. DISC1 is known to co-aggregate with two proteins associated with neurodegenerative disorders, huntingtin and TDP-43, as well as other proteins implicated in mental illness. We have investigated the aggregation propensity and novel interactors of DISC1 in HEK293T cell culture using co-expression with another protein implicated in neurodegenerative disorders, Fused in Sarcoma protein (FUS). Microscopic examination of cells overexpressing full length DISC1 and FUS mutant types showed that DISC1 can be recruited to FUS protein aggregates. In similar conditions no aggregation was observed between FUS and Trio and F-actin binding protein 1 (TRIOBP-1), a schizophrenia related protein. We conclude that co-aggregation between DISC1 and FUS protein represents a potential direction in future research as one of the molecular processes involved in development of neuropsychiatric disorders.Šizofrenija i kronični afektivni poremećaji kao što su depresija i bipolarni poremećaj su nedovoljno istraženi poremećaji koji su jedan od vodećih uzroka invalidnosti. Dijagnoza ovih stanja je bazirana isključivo na psihijatrijskom intervjuu. Potrage za biološkim markerima boesti ukazale su da agregacija proteina i promjene homeostaze proteina mogu biti jedan od potencijalnih faktora kod pojave mentalnih bolesti.
Poremećen u šizofreniji 1 (DISC1, eng: Disrupted in Schizophrenia 1) je jedan od proteina koji tvore aggregate u mozgu pacijenata. DISC1 je protein koji ostvaruje interakcije sa mnoštvom proteina. Pokazano je da DISC1 tvori aggregate sa huntingtinom i TDP-43, proteinima prisutnima u neurodegenerativnim bolestima, te sa proteinima prisutnima u mentalnim bolestima. Ovdje smo istražili sklonost agregiranju i nove interakcije DISC1 proteina u HEK293T staničnoj liniji pomoću zajedničke ekspresije DISC1 i Spojen u Sarkomu (FUS-a, eng: Fused in Sarcoma), proteina povezanog sa neurodegenerativnim bolestima. Mikroskopska analiza prekomjerne ekspresije cijelokupnog DISC1 proteina i FUS mutantskih verzija proteina je pokazala da je DISC1 regrutiran u FUS aggregate. U sličnim uvjetima nije pokazana zajednička agregacija između FUS-a i Trio i F-vezujućeg proteina 1 (TRIOBP-1, eng: Trio and F-actin binding protein 1), povezanog sa shizofrenijom. Zaključujemo da zajednička agregacija DISC1 i FUS-a predstavlja obećavajući pravac prema budućim istraživanjima kao jedan od molekularnih procesa uključenih u razvoj neuropsihijatrijskih poremećaja
Sucrose, glucose and fructose binding to tribomechanically micronised clinoptilolites and zeolite A
No full textZeoliti su alumosilikati prirodnog ili sintetičkog porijekla, čiji biotehnološki značaj leži u njihovoj velikoj moći sorpcije tvari, ionskoj izmjeni i površinskoj aktivnosti. Klinoptilolit je jedna vrsta prirodnog zeolita koji se pokazao sigurnim za ingestiju u ljudi, a zeolit A je sintetička vrsta zeolita i ujedno zeolit s najširom upotrebom u industriji. Već je dokazano da pojedini zeoliti adsorbiraju saharozu, glukozu i fruktozu i tako spuštaju koncentracije šećera, stoga je cilj ovog istraživanja bio provjeriti može li se isto postići uporabom tribomehanički mikroniziranih klinoptilolita i zeolita A. Tribomehanički mikronizirani klinoptiloliti jesu čestice manjih veličina i većih aktivnih površina. U našem istraživanju koristili smo jednostruko (TMAZ), dvostruko (PMA) i oksigenirano dvostruko tribomehanički mikronizirane (PMA-O2) klinoptilolite. U vodi smo zasebno otopili i miješali četiri zeolita s pojedinim šećerom (saharozom, glukozom i fruktozom). Nakon jednodnevnog inkubiranja na refraktometru smo provjerili kakve su koncentracije otopina šećera i zeolita usporedno s kontrolama. Rezultati koje smo dobili pokazuju kako prisutnost zeolita u otopinama smanjuje koncentracije šećera. Nadalje, ustanovili smo da nema razlika u smanjenju koncentracije šećera s obzirom na vrstu zeolita, niti s obzirom na vrstu šećera koje smo koristili.Zeolites are alumosillicates of natural or synthetic origin, important in biotechnology because of their great sorption and ion exchange properties along with surface activity. Clinoptilolite is a natural zeolite which has been proven to be safe for human ingestion and zeolite A is a synthetic form with the widest use in industry. It has already been proven that certain zeolites adsorbe sucrose, glucose and fructose and in that way lower sugar concentrations, so the purpose of this research was to check if the same outcome could be achieved using tribomechanically micronized clinoptilolites and zeolite A. Tribomechanically micronized clinoptilolites have smaller sized particles and greater surface area. In our study we used micronized (TMAZ), double micronized (PMA) along with double micronized and oxygenated (PMA-O2) clinoptilolites. In water we dissolved the four zeolites separately and mixed in either sucrose, glucose or fructose. After a day of incubation, we checked the concentrations of smples with zeolites and sugars and control samples on refractometer. The results show that in the presence of zeolites concentrations of sugars in solution drop compared to control. We also found out that among the four zeolites we used and among the three sugars we used, there are no differences in efficacy of lowering of sugar concentrations in solutions