Repository of the University of Rijeka, Department of Biotechnology
Not a member yet
715 research outputs found
Sort by
Computational and experimental therapeutic efficacy analysis of andrographolide phospholipid complex self-assembled nanoparticles against Neuro2a cells
No full textBackground: Neuroblastoma is one of the most common malignancies in childhood, accounts for approximately 7% of all malignancies. Andrographolide (AN) inhibits cancer cells progression via multiple pathways like cell cycle arrest, mitochondrial apoptosis, NF-κβ inhibition, and antiangiogenesis mechanism. Despite multiple ad vantages, application of AN is very limited due to its low aqueous solubility (6.39 ± 0.47 μg/mL), high lip ophilicity (log P ~ 2.632 ± 0.135), and reduced stability owing to pH sensitive lactone ring. Objectives and results: In present investigation, a molecular complex of AN with soya-L-α-phosphatidyl choline (SPC) was synthesized as ANSPC and characterized by FT-IR and1H NMR spectroscopy. Spectral and molecular simulation techniques confirmed the intermolecular interactions between the 14-OH group of AN and the N+(CH3)3part of SPC. In addition, molecular dynamics (MD) simulation was used to determine the degree of interaction between various proteins such as TNF-α, caspase-3, and Bcl-2. Later, ANSPC complex was trans formed in to self-assembled soft nanoparticles of size 201.8 ± 1.48 nm with PDI of 0.092 ± 0.004 and zeta potential of −21.7 ± 0.85 mV. The IC50 offree AN (8.319 μg/mL) and the self-assembled soft ANSPC nano particles (3.406 μg/mL ~ 1.2 μg of AN) against Neuro2a cells was estimated with significant (P < 0.05) dif ference. Interestingly, the self-assembled soft ANSPC nanoparticles showed better endocytosis compared to free AN in Neuro2a cells. In-vitrobiological assays confirmed that self-assembled soft ANSPC nanoparticles induces apoptosis in Neuro2a cells by declining the MMP (Δψm) and increasing the ROS generation. Conclusion: Self-assembled soft ANSPC nanoparticles warrant further in-depth antitumor study in xenograft model of neuroblastoma to establish the anticancer potential.Trajektroije su dobivene pomoću paketa za molekulsku dinamiku Amber 1
Odnos između cannabisa i schizofrenije
No full textSchizophrenia is a severe mental disorder typically accompanied by a
combination of positive and negative symptoms as well as cognitive
impairment. The cause of its development is not yet known but studies
suggest that genes and environmental factors play a part in its
manifestation. Cannabis is one of the things that has been connected to a
higher risk of schizophrenia development. While some evidence suggests
cannabis has a causal role in the disorder developing, other sources claim
that it affects only genetically predisposed individuals. There is a third theory
which states that cannabis use has an impact in the progression of
schizophrenia while its usage is more prevalent in those genetically
predisposed to schizophrenia. This thesis presents studies that have
researched these hypotheses as well as cannabis itself and its compounds.
Additionally, it considers the ethical and societal implications of cannabis
legalization, particularly in relation to schizophrenia. These theories
altogether suggest a complex interaction where cannabis may act as a
catalyst in genetically susceptible individuals while potentially exacerbating
the disorder in those already affected. This thesis gives a better
understanding of the intricate link between cannabis and schizophrenia
which is of great importance for public health policies
Implemmentation of SGLT1 and SGLT2 beyond type 2 diabetes
No full textRad istražuje primjenu SGLT1 i SGLT2 inhibitora izvan okvira
konvencionalnog liječenja dijabetesa tipa 2 (T2DM), usredotočujući se na
njihove potencijalne koristi u različitim kliničkim kontekstima i stanjima.
Dok su inhibitori SGLT2, kao što su kanagliflozin, dapagliflozin,
empagliflozin i ertugliflozin, prvenstveno razvijeni za snižavanje razine
glukoze u krvi kod T2DM pacijenata, istraživanja su pokazala da imaju
dodatne koristi u liječenju kardiovaskularnih bolesti, zaštiti bubrega, te
onkologiji. Inhibitori SGLT1, primjerice sotagliflozin, djeluju na smanjenje
apsorpcije glukoze u gastrointestinalnom traktu i također mogu smanjiti
postprandijalnu hiperglikemiju. Sotagliflozin, kao dualni inhibitor SGLT1 i
SGLT2, pokazuje obećavajuće rezultate u poboljšanju kontrole glikemije,
neovisno o inzulinu, a može biti koristan i kod pacijenata s dijabetesom tipa
1 (T1DM). Osim toga, pokazuje se da SGLT1 i SGLT2 inhibitori imaju i
potencijal u liječenju drugih stanja, uključujući bolesti srca i bubrežnu
insuficijenciju. Rad također razmatra izazove i rizike povezane s primjenom
ovih inhibitora izvan dijabetesa, kao što su povećani rizik od dijabetičke
ketoacidoze (DKA) i potreba za pažljivim praćenjem bolesnika. Zaključuje
se da su SGLT1 i SGLT2 inhibitori u fazi istraživanja za proširenje njihove
primjene izvan T2DM, a njihova primjena u drugim kliničkim situacijama
može ponuditi nove terapijske opcije i poboljšati ishode za pacijente s
različitim zdravstvenim problemima.The paper explores the application of SGLT1 and SGLT2 inhibitors beyond
the conventional treatment of type 2 diabetes mellitus (T2DM), focusing on
their potential benefits in various clinical contexts and conditions. While
SGLT2 inhibitors, such as canagliflozin, dapagliflozin, empagliflozin, and
ertugliflozin, were primarily developed to lower blood glucose levels in T2DM
patients, research has shown that they offer additional benefits in the
treatment of cardiovascular diseases, renal protection, and oncology.
SGLT1 inhibitors, such as sotagliflozin, work by reducing glucose absorption
in the gastrointestinal tract and can also decrease postprandial
hyperglycemia. Sotagliflozin, as a dual SGLT1 and SGLT2 inhibitor, shows
promising results in improving glycemic control independently of insulin and
may be beneficial for patients with type 1 diabetes mellitus (T1DM).
Additionally, SGLT1 and SGLT2 inhibitors exhibit potential in treating other
conditions, including heart diseases and renal insufficiency. The paper also
discusses the challenges and risks associated with using these inhibitors
outside of diabetes, such as the increased risk of diabetic ketoacidosis
(DKA) and the need for careful patient monitoring. It is concluded that
SGLT1 and SGLT2 inhibitors are in the research phase for expansion of their
use beyond T2DM, and their application in other clinical situations may offer
new therapeutic options and improve outcomes for patients with various
health issues
The role of gut microbiota alterations in irritable bowel syndrome
No full textSindrom iritabilnog crijeva je česta dijagnoza u današnjem modernom svijetu, koja najčešće pogađa žene. Pojavljuje se sa simptomima poremećaja pokretljivosti crijeva i visceralne preosjetljivosti, a vjeruje se da većina pacijenata ima izmijenjenu mikrobiotu crijeva koja sudjeluje u patogenezi sindroma, no način na koji se to zbiva za sada nije u potpunosti razjašnjen. Dijeli se na nekoliko podtipova s obzirom na učestalost i konzistentnost stolice, a mnogi rizični čimbenici povezuju su se nastankom ovog poremećaja. Zbog nepostojanja adekvatnih biomarkera, sindrom je teško dijagnosticirati te još teže liječiti, a zabilježene promjene u mikrobioti crijeva ne moraju postajati u svih pacijenata ili poklapati se u svim slučajevima. Sve od navedenog otežava proučavanje procesa nastanka ovog poremećaja i njegove povezanosti s neuroimunološkim i neuroendokrinim sustavom, za koje se pretpostavlja da su u čvrstoj interakciji. U ovom radu sadržan je kratki pregled trenutnih saznanja o sindromu iritabilnog crijeva, kako je on povezan s promjenama u ravnoteži mikrobiote crijeva te kakav utjecaj na njegov razvoj imaju prehrana i psihološki stres.Irritable bowel syndrome is a common diagnosis in today's modern world, which mostly affects women. It appears with symptoms of intestinal motility disorders and visceral hypersensitivity, and it is believed that most patients have an altered gut microbiota that participates in the pathogenesis of the syndrome in a way that is not yet fully understood. It is divided into several subtypes with regard to stool frequency, and many risk factors are associated with the occurrence of this disorder. Due to the lack of adequate biomarkers, the syndrome is difficult to diagnose and even more difficult to treat, and recorded changes in the gut microbiota may not occur in all patients or coincide in all cases. All of the above makes it difficult to study the process of the emergence of this disorder and its connection with the neuroimmunological and neuroendocrine systems, which are assumed to be in a tight interaction. This thesis contains a brief overview of current knowledge about irritable bowel syndrome, how it is related to changes in the balance of intestinal microbiota a
Heat shock proteins (HSPs) and diabetes
No full textProteini toplinskog šoka (eng. heat shock proteins, HSPs) visoko su očuvana obitelj proteina koje eksprimiraju sve stanice izložene okolišnom stresu i imaju različite funkcije. Razvrstani su u 7 glavnih obitelji prema molekulskoj masi: HSP10 (HSPE); mali HSP molekulske mase od 12-43 kDa (npr. HSP27 ili HSPB1); HSP40 (DNAJ); HSP60 (HSPD); HSP70 (HSPA); HSP90 (HSPC) i HSP100. Kao molekularni šaperoni u fiziološkim uvjetima promiču ispravno savijanje proteina.
HSP-i su bitni u mnogim staničnim procesima, od regulacije staničnog ciklusa, do sudjelovanja u procesu apoptoze (vazorelaksacija, stabilizacija aktina, funkcija šaperona, funkcije preživljavanja apoptozom, antioksidativno djelovanje, protuupalno djelovanje, itd.). HSP-i su povezani s uzrocima šećerne bolesti tipa 1 i u liječenju inzulinske rezistencije kod šećerne bolesti tipa 2 i pretilosti. Nedavne studije su pokazale da su HSP-i uključeni u patogeneze bolesti raka, neurodegenerativnih bolesti, bolesti krvožilnog sustava i u autoimunih bolesti te da su povezani s nizom kliničkih stanja kao što je dijabetes i njegove posljedice (angiopatija, neuropatija, retinopatija, nedostatak antioksidacijskog obrambenog sustava i poremećaj lipidnog profila te kronična hiperglikemija).
U ovim bolestima su specifični HSP-i eksprimirani ili suprimirani pa se mogu koristiti kao potencijalne dijagnostičke i terapijske mete. Naravno, za to su potrebne vrlo osjetljive i pouzdane analitičke metode za njihovo određivanje.
Ovaj pregledni rad opisuje svojstva HSP-a, karakterizaciju i strukturu, biološke funkcije, prisutnost i poremećaj HSP-a u dijabetesu i sekundarnim komplikacijama dijabetesa.Heat shock proteins (HSPs) are a highly conserved family of proteins that are expressed by all cells exposed to environmental stress and have different functions. They are categorised into 7 main families according to their molecular weight: HSP10 (HSPE); small HSPs with a molecular weight of 12-43 kDa (e.g., HSP27 or HSPB1); HSP40 (DNAJ); HSP60 (HSPD); HSP70 (HSPA); HSP90 (HSPC) and HSP100. As molecular chaperones, they promote the correct folding of proteins under physiological conditions.
HSPs are essential for many cellular processes, from regulation of the cell cycle to involvement in the process of apoptosis (vasorelaxation, actin stabilisation, chaperone function, apoptosis survival functions, antioxidant activity, anti-inflammatory activity, etc.). HSPs are associated with the causes of type 1 diabetes and in the treatment of insulin resistance in type 2 diabetes and obesity. Recent studies have shown that HSPs are involved in the pathogenesis of cancer, neurodegenerative diseases, diseases of the circulatory system and in autoimmune diseases and that they are associated with a number of clinical conditions such as diabetes and its consequences (angiopathy, neuropathy, retinopathy, lack of antioxidant defence system and lipid profile disturbance and chronic hyperglycemia).
In these diseases, certain HSPs are expressed or suppressed so that they can be used as potential diagnostic and therapeutic targets. This, of course, requires very sensitive and reliable analytical methods for their determination.
This review describes the properties of HSPs, their characterisation and structure, their biological functions and the presence and disruption of HSPs in diabetes and secondary complications of diabetes
The role of Epstein-Barr virus in the pathogenesis of multiple sclerosis
No full textMultipla skleroza (MS) je autoimuna bolest koja prvenstveno zahvaća središnji živčani sustav (SŽS). Jedno od patoloških obilježja MS-a je povećana propusnost krvno-moždane barijere (BBB, prema engl. blood-brain barrier) što omogućuje ulazak autoreaktivnih stanica u SŽS gdje uzrokuju kroničnu upalu i oštećenje mijelina. Demijelinizacijom se narušava prijenos akcijskog potencijala koji je esencijalan za motoričke, senzoričke i kognitivne funkcije. Budući da do demijelinizacije može doći u bilo kojem dijelu SŽS-a bolest se očituje brojnim simptomima, a neki od njih su slabost mišića, umor, problemi s vidom, problemi s kognicijom te mnogi drugi. Epstein-barr virus (EBV) je herpesvirus te se njegov životni ciklus sastoji od primarne infekcije koja započinje infekcijom epitelnih stanica te je u djece najčešće asimptomatska, dok u adolescenata i odraslih najčešće rezultira infektivnom mononukleozom. Potom virus uspostavlja latentnu fazu inficiranjem B limfocita, a budući da u latentnoj fazi gotovo i nema ekspresije gena postaje nevidljiv za imunosni sustav. Stanja poput stresa, kronične bolesti i imunosupresije mogu potaknuti litičku reaktivaciju čime virus ponovno ima sposobnost infekcije drugih stanica. EBV se dugi niz godina povezuje s MS-om, a novija istraživanja jasno pokazuju njegovu nužnost u patogenezi MS-a u genetski predisponiranih osoba. Iako mehanizam bolesti nije razjašnjen, nagađa se kako je molekularna mimikrija jedan od mogućih patogenetskih mehanizama. Kako je disfunkcija imunosnog sustava najvažnija za razvoj MS-a sve danas dostupne terapije fokusiraju se na njegovu regulaciju. Budući da je poznata važnost EBV-a u patogenezi MS-a, provedeno je nekoliko istraživanja za učinkovitost antiviralnih lijekova, no nisu pokazala zadovoljavajuće rezultate. Stoga je sve više istraživanja usmjereno na razvoj polivalentnih cjepiva kojima bi se mogla spriječiti primarna infekcija.Multiple sclerosis (MS) is an autoimmune disease that primarily affects the central nervous system (CNS). One of the pathological features of MS is the increased permeability of the blood-brain barrier (BBB), which allows autoreactive cells to enter the CNS, where they cause chronic inflammation and damage to myelin. Demyelination impairs the transmission of the action potential, which is essential for motor, sensory and cognitive functions. Since demyelination can occur in any part of the CNS, the disease is manifested by numerous symptoms, some of which are muscle weakness, fatigue, vision problems, cognitive problems, and many others. Epstein-Barr virus (EBV) is a herpesvirus and its life cycle consists of a primary infection that begins with an infection of epithelial cells, which is most often asymptomatic in children, while in adolescents and adults it most often results in infectious mononucleosis. The virus then establishes a latent phase by infecting B lymphocytes, and since there is almost no gene expression in the latent phase, it becomes invisible to the immune system. Conditions such as stress, chronic illness, and immunosuppression can trigger lytic reactivation, whereby the virus regains the ability to infect other cells. EBV has been associated with MS for many years, and recent research clearly shows its necessity in the pathogenesis of MS in genetically predisposed individuals. Although the mechanism of the disease has not been clarified, it is speculated that molecular mimicry is one of the possible pathogenetic mechanisms. As the dysfunction of the immune system is the most important for the development of MS, all therapies available today focus on its regulation. Since the discovery of the importance of EBV in MS pathogenesis, several studies have been carried out for the effectiveness of antiviral drugs, but they did not show satisfactory results. Therefore, more and more research is focusing on the development of polyvalent vaccines that could prevent primary EBV infection
Selenoproteins and their importance in everyday life
No full textSelenij je nemetal koji se pojavljuje u tragovima u živome svijetu, a njegova najveća značajnost se pokazala u proučavanju selenoproteina - proteina koji u svojoj primarnoj strukturi sadrže aminokiselinu cisteina sa atomom selenija umjesto sumpora. Glavna svrha rada je prikazati važnost ugradnje selenija u cistein te kako selenij u aminokiselini omogućuje proteinima vršenje različitih životnih i fizioloških funkcija. Znanje rada o selenoproteinima počiva na znanstvenim člancima koji opisuju na koji način se sintetiziraju, koje vrste postoje i koje su njihove glavne funkcije te koja je njihova značajnost u drugim organizmima i pri razvoju bolesti. Pregledom znanstvenih članaka na temu selenoproteina nastoji se u ovom radu obuhvatiti i sažeti važnost selenoproteina u svakodnevnom životu. U radu se koriste metode indukcije i dedukcije. Rezultati su postignuti navedenim metodama te su analizom podataka upotpunjene činjenice o seleniju i selenoproteinima. Generalni zaključak rada je potaknuti na važnost selenija jer bez obzira što je selenij element u tragovima, ne može se zanemariti njegova važnost u biologiji u obliku selenoproteina. Nedostatak selenija, i time disfunkcija selenoproteina, dovodi do raznih poremećaja u organizmu zbog čega je potrebno usmjeriti se ka ovom području istraživanja.Selenium is a non-metal, a trace element in the living world, and its greatest importance was shown in the study of selenoproteins - proteins which in their primary structure contain the amino acid cysteine with a selenium atom instead of sulphur. The main purpose of the thesis is to show the importance of incorporating selenium into cysteine and how selenium in an amino acid enables proteins to perform various life and physiological functions. Knowledge of this thesis about selenoproteins is based on scientific articles that describe how they are synthesized, what types exist and what their main functions are and what is their importance in other organisms and in the development of diseases. By reviewing scientific articles on the topic of selenoproteins, this paper tries to cover and summarize the importance of selenoproteins in everyday life. The paper uses the methods of induction and deduction. The results were achieved by the mentioned methods and the facts about selenium and selenoproteins were completed by data analysis. The general conclusion of the paper is to encourage the importance of selenium, because regardless of the fact that selenium is a trace element, its importance in biology in the form of selenoproteins cannot be ignored. Selenium deficiency, and thus selenoprotein dysfunction, leads to various disorders in the body, which is why it is necessary to focus on this area of research
Otkrivanje veze između normalnog razvoja i nastanka raka mozga
No full textNeural stem cells are a group of cells capable of self-renewal and differentiation into various subtypes. Proper regulation of these cells is essential for normal development and function of the central nervous system. When this regulation fails, it can result in the formation of tumors, such as gliomas.
In this thesis, we tried to clarify the relationship between neurogenesis and tumor formation, emphasizing the molecular and cellular mechanisms that potentially drive the process of tumorigenesis. By synthesizing current research on the expression of transcription factors and genes involved in both neurogenesis and tumorigenesis, this thesis aims to highlight critical pathways and factors in brain tumor development. Identifying the cell of origin for each tumor type can reveal lineage-specific therapeutic vulnerabilities and opportunities to detect early malignant or even premalignant abnormal cell states, as certain cells may be more susceptible to oncogenic attacks than others. Understanding these mechanisms may reveal new therapeutic targets and strategies for preventing and treating brain cancer.Neuralne matične stanice su skupina stanica koja ima sposobnost samoobnavljanja i diferencijacije u različite podtipove. Pravilna regulacija ovih stanica ključna je za normalan razvoj i funkcioniranje središnjeg živčanog sustava. Kada ova regulacija zakaže, to može rezultirati formiranjem tumora, kao što su gliomi.
U ovom radu, pokušali smo razjasniti odnos između neurogeneze i nastanka tumora, ističući molekularne i stanične mehanizme koji potencijalno pokreću proces tumorigeneze. Pregledom trenutnih istraživanja o ekspresiji transkripcijskih faktora i gena uključenih i u neurogenezu i u tumorigenezu, ovaj rad nastoji istaknuti ključne puteve i faktore u razvoju tumora mozga. Identificiranje podrijetla stanice za svaku vrstu tumora može otkriti specifične terapijske slabosti i mogućnost ranog otkrivanja malignih ili čak pre-malignih abnormalnih stanja stanica, budući da određene stanice mogu biti osjetljivije na onkogene napade od drugih. Razumijevanje ovih mehanizama može otkriti nove terapijske mete i strategije za prevenciju i liječenje raka mozga
New scavengers for carbon dioxide capture for metal-catalyzed carbonate synthesis
No full textOvaj istraživački rad fokusira se na dobivanje organskih cikličkih karbonata direktnom sintezom iz CO2. Kako bi poslužili kao supstrati, prvo su sintetizirani različiti derivati propagilnog alkohola. Ciklički karbonati su dobiveni kroz trokomponentnu reakciju kataliziranu metalom, uključujući odgovarajući propargilni alkohol, plinoviti CO2 pod atmosferskim tlakom i alilni elektrofil. U svrhu postizanja visokog iskorištenja provedena je optimizacija reakcijskih uvjeta za sintezu ciljnog cikličkog karbonata korištenjem bakrenih ili paladijevih katalizatora. Dobiveni produkti, supstrati propargilnog alkohola i karbonati, pročišćeni su kromatografijom na koloni te su karakterizirani infracrvenom spektroskopijom (IR) i spektroskopijom nuklearne magnetske rezonancije (NMR). U ovom radu su opisani načini dobivanja svakog pojedinog produkta, njegova karakterizacija te daljnja upotreba
Exploring potential inhibitors against Kyasanur forest disease by utilizing molecular dynamics simulations and ensemble docking
No full textKyasanur forest disease (KFD) is a tick-borne, neglected tropical disease, caused by KFD virus (KFDV) which belongs to Flavivirus (Flaviviridae family). This emerging viral disease is a major threat to humans. Currently, vaccination is the only controlling method against the KFDV, and its effectiveness is very low. An effective control strategy is required to combat this emerging tropical disease using the existing resources. In this regard, in silico drug repurposing method offers an effective strategy to find suitable antiviral drugs against KFDV proteins. Drug repurposing is an effective strategy to identify new use for approved or investigational drugs that are outside the scope of their initial usage and the repurposed drugs have lower risk and higher safety compared to de novo developed drugs, because their toxicity and safety issues are profoundly investigated during the preclinical trials in human/other models. In the present work, we evaluated the effectiveness of the FDA approved and natural compounds against KFDV proteins using in silico molecular docking and molecular simulations. At present, no experimentally solved 3D structures for the KFD viral proteins are available in Protein Data Bank and hence their homology model was developed and used for the analysis. The present analysis successfully developed the reliable homology model of NS3 of KFDV, in terms of geometry and energy contour. Further, in silico molecular docking and molecular dynamics simulations successfully presented four FDA approved drugs and one natural compound against the NS3 homology model of KFDV