Trefoil Factor 3 Protein and Sepsis – A Review

Sepsis is one of the most common causes of death in hospitalized patients. Disruption of intestinal barrier homeostasis is one of its main hallmarks. Trefoil factor family proteins are known for their role in protecting and repairing the intestinal mucosa. It has been repeatedly shown that the TFF3 protein is involved in maintaining the intestinal barrier. For that reason, it has been studied in the search for objective measures to predict the onset or outcome of sepsis. Several studies have been performed on rodent sepsis models and on sepsis patients, both children and adults. From the limited research available to date, it appears that TFF3 is involved in the pathogenesis of sepsis, but the exact mechanism is not yet clear. Its potential as a sepsis biomarker has so far been low, but more extensive studies on its role in predicting disease severity and outcome, as well as organ dysfunction, may lead to finding specific patient groups or sepsis stages for which it would be suitable

Global methods approach in deciphering the role of TFF2 proteins in organism

Tijekom posljednjih petnaestak godina za istraživanje uloge različiti h proteina i mehanizama nastanka bolesti primjenjuju se sistemski pristupi i analize kojima se istovremeno prate globalne promjene razine ekspresije velikog broja gena i/ili proteina. Imajući na umu složene interakcije na razini stanica i činjenicu kako je većina bolesti multi faktorijalnog podrijetla, takav sistemski pristup najbolji je način stjecanja uvida u funkciju nekog proteina i/ili mehanizme nastanka bolesti . Proteini “Trefoil Factor Family” ili proteini TFF (TFF1,TFF2, TFF3) otkriveni su prije više od 25 godina, te je ubrzo postalo jasno kako je njihova uloga u organizmu iznimno kompleksna. Tek je sistemski pristup istraživanju analize uloge proteina TFF2 razjasnio njegovu ulogu u organizmu pokazujući vezu s imunološkim sustavom.In the last fi ft een years a systemic approach has been widely implemented in the investi gati on of diff erent proteins’ functi on as well as to elucidate the mechanisms underlying disease development. Simultaneous monitoring of global changes through gene expression studies combined with protein patt ern analyses represents the best way to unveil the functi on of some proteins and/or pathogenesis mechanisms for various disease especially when knowing that multi ple interacti on patt erns are present inside the cells and that causes of diseases are oft en multi factorial. Trefoil factor family proteins (TFFs) have been discovered more than 25 years ago. It has soon become clear that their role in biological systems is multi factorial and quite complex. A systemic approach to their analyses brought out the role of TFF2 involvement in the processes relevant for the immune system

Localization of trefoil factor family peptide 3 (TFF3) in epithelial tissues originating from the three germ layers of developing mouse embryo

Trefoil factor family (TFF) peptides are involved in the maintenance of epithelial integrity and epithelial restitution. Mature epithelial tissues originate from different embryonic germ layers. The objective of this research was to explore the presence and localization of TFF3 peptide in mouse embryonic epithelia and to examine if the occurrence of TFF3 peptide is germ layer-dependent. Mouse embryos (14-18 days old) were fixed in 4% paraformaldehyde and embedded in paraffin. Immunohistochemistry was performed with affinity purified rabbit anti-TFF3 antibody, goat anti-rabbit biotinylated secondary antibody and streptavidin-horseradish peroxidase, followed by 3, 3’-diaminobenzidine. TFF3 peptide was present in the gastric and intestinal mucosa, respiratory mucosa in the upper and lower airways, pancreas, kidney tubules, epidermis, and oral cavity. The presence and localization of TFF3 peptide was associated with the embryonic stage and tissue differentiation. TFF3 peptide distribution specific to the germ layers was not observed. The role of TFF3 peptide in cell migration and differentiation, immune response, and apoptosis might be associated with specific embryonic epithelial cells. TFF3 peptide may also be considered as a marker for mucosal maturation

Novel Expression Patterns for Trefoil Peptides: Presence of Tff2 and Tff3 in Rodent Cochlea

Trefoil peptides: Tff1, Tff2 and Tff3, assigned to the so-called trefoil factor family (TFF), are secretory proteins predominantly expressed by the gastrointestinal (GI) epithelial cells. Their multiple protective functions include an important role in immune response and apoptosis. Here, a novel localization of Tff2 and Tff3 in the cochlea of mouse inner ear is presented. Tffs expression and localization in mouse cochlea was analyzed by using the quantitative real time PCR (qPCR) and immunohistochemistry. Tff2 and Tff3 mRNA quantification by qPCR showed their presence in the cochlea. Immunohistochemistry demonstrated the presence of Tff2 in the spiral ligament and limbus and for Tff3 in the spiral ligament and the organ of Corti. These new and surprising findings of Tff’s presence in the cochlea indicate a new role of TFFs connected with the organ of hearing which still needs to be physiologically evaluated

Molekularno-citogenetičko proučavanje heterocromatina u nekih kornjaša

Heterochromatin characteristics have been studied in Leptinotarsa decemlineata belonging to the leaf beetles (Chrysomelidae) and compared to the thoroughly analysed heterochromatin of the mealworm beetle Tenebrio molitor, representing darkling beetles (Tenebrionidae). C-banding reveals heterochromatin in pericentromeric regions of all chromosomes of both species; however heterochromatic blocks of L. decemlineata are significantly smaller in size. Digestion of L. decemlineata genomic DNA with 12 restriction enzymes reveals presence of bands characteristic for repetitive DNA, but again in a significantly lower amount than those found in genomic DNA of T. molitor. While T. molitor exhibits complete correspondence of restriction enzyme effects on naked DNA and mitotic chromosomes, L. decemlineata mitotic chromosomes are resistant to the digestion with restriction enzymes. The results show that two species have similar organization of heterochromatin on chromosomes but differ significantly in its amount. In addition, difference in accessibility to in situ restriction enzyme digestion indicates specificity of heterochromatin structure in the two species.Proučavan je heterokromatin u krumpirove zlatice Leptinotarsa decemlineata kao predstavnice zlatnica (Chrysomelidae), te je uspoređen s detaljno opisanim heterokromatinom brašnara Tenebrio molitor, kao predstavnika crnokrilaca (Tenebrionidae). Metoda C-pruganja je pokazala prisutnost heterokromatina u pericentromernim područjima svih kromosoma obiju vrsta, iako je njegov udio znatno manji u krumpirove zlatice. Razgradnja genomske DNA krumpirove zlatice sa 12 restrikcijskih enzima otkrila je prisutnost ponovljene DNA, ali opet u znatno manjoj količini u odnosu na brašnara. Iako kod brašnara T. molitor postoji podudarnost u razgradnji DNA i mitotskih kromosoma restrikcijskim enzimima, mitotski kromosomi krumpirove zlatice su otporni na razgradnju restrikcijskim enzimima. Rezultati pokazuju da obje vrste imaju podjednaku organizaciju heterokromatina na kromosomima unatoč velikoj razlici u količini. Pored toga, razlika u razgradnji mitotskih kromosoma restrikcijskim enzimima ukazuje na specifičnost heterokromatinske strukture u ovih vrsta

Antineoplastic DNA-binding compounds: intercalating and minor groove binding drugs

DNA intercalating and minor groove binding compounds are new weapons in the battle against malignant diseases. These antineoplastic agents target the DNA molecule and interfere with the cell cycle leading to rapidly proliferating cell death. They are mainly derivates of a naturally occurring organic compound derived from a microorganism or plant. Intercalators usually act as topoisomerase I and/or II poisons, while the mechanisms of DNA minor groove binders are a combination of several steps including topoisomerase poisoning. This paper gives an overview of some of the developed DNA intercalating and minor groove binding compounds, as well as an explanation of their chemical structures, origins, and application in chemotherapy

Influence of Allergy and Bacterial Colonization on the Quality of Life in Nasal Polyposis Patients

Allergies and bacterial colonization are frequently found in patients with chronic rhinosinuitis with nasal polyposis (CRSwNP). The aim of this study was to identify patients with allergy and present microorganisms in ethmoid sinus among the patients with refractory CRSwNP undergoing surgical treatment at the University Hospital Centre Osijek, and to compare their life quality, defined by SNOT-20 analysis (sinonasal outcome test) to the rest of patients, and a con- trol group consisting of patients undergoing septoplasty but free of allergy and/or CRS. An additional aim was to iden- tify specific types and strains of microorganisms (bacteria and fungi) found in these patients, in order to compare them to other reports, and to revise the empirical antimicrobial therapy. In this paper we demonstrate a high incidence of bacte- rial colonization (83.3%) among CRSwNP patients. As in previous studies, gram positive aerobes were the most fre- quently isolated bacteria and all of them were covered by specific antibiotics given before the specimen collection. Allergy was found in only 20% of these patients, who presented with a reduced quality of life when compared to the control group and CRSwNP without allergy. Significantly more frequent dominant symptoms in these patients were cough, frustration and irritation. In the line with this finding is the objective assessment by endoscopy (Malm score) that showed more prominent nasal polyposis in allergy patients

Izražaj TFF gena i proteina u tumorima dojke

The objective of this study was to determine diff erential expression of TFF1, TFF2 and TFF3 genes and proteins in breast tumor subtypes. In addition, we investigated the correlation between TFF genes within tumor subgroups, and TFF genes with clinical and pathologic characteristics of the tumor. Study group included 122 patients with surgically removed breast tumors. Samples were investigated using qRT-PCR and immunohistochemistry. TFF1 and TFF3 genes and proteins were expressed in breast tumors, while the levels of TFF2 gene and protein expression were very low or undetectable. TFF1 was signifi cantly more expressed in benign tumors, while TFF3 was more expressed in malignant tumors. Gene and protein expression of both TFF1 and TFF3 was greater in lymph node-negative tumors, hormone positive tumors, tumors with moderate levels of Ki67 expression, and in grade II tumors. A strong positive correlation was found between TFF1 and TFF3 genes, and the expression of both negatively correlated with Ki67 and the level of tumor histologic diff erentiation. Our results suggest that TFF1 and TFF3, but not TFF2, may have a role in breast tumor pathogenesis and could be used in the assessment of tumor diff erentiation and malignancy.Cilj ovoga istraživanja bio je utvrditi razlike u izražaju gena i proteina TFF1, TFF2 i TFF3 u različitim vrstama tumora dojke te ispitati korelacije između gena TFF i vrsta tumora te gena TFF i kliničko-patoloških karakteristika tumora. U studiju su bile uključene 122 ispitanice kojima je kirurški odstranjen tumor dojke. Uzorci su obrađeni metodom qRT-PCR i metodom imunohistokemije. Geni i proteini TFF1 i TFF3 bili su izraženi u tumorima dojke, dok izražaj gena i proteina TFF2 nije otkriven u tumorskom tkivu. TFF1 je bio izraženiji kod dobroćudnih tumora, dok je TFF3 bio izraženiji kod zloćudnih tumora. TFF1 i TFF3 su bili izraženiji u hormonski ovisnim tumorima, tumorima bez metastaza u limfnim čvorovima, tumorima s umjereno visokim izražajem Ki67 i umjereno diferenciranim tumorima. Jaka pozitivna korelacija uočena je između gena TFF1 i TFF3, a oba su negativno korelirala s faktorom Ki67 i stupnjem diferenciranosti tumora. Dobiveni rezultati pokazuju kako bi TFF1 i TFF3 mogli imati ulogu u patogenezi tumora dojke te bi se potencijalno mogli rabiti za određivanje tumorskog statusa i procjenu malignosti tumora

Biological Activity of Phenolic Compounds in Extra Virgin Olive Oils through Their Phenolic Profile and Their Combination with Anticancer Drugs Observed in Human Cervical Carcinoma and Colon Adenocarcinoma Cells

The roles of phenolics from olive oils as effective anticancer agents have been documented in various in vitro studies of different cancer cells lines, but the relationship between the phenolic profile of olive oil and its biological activity needs more elucidation. In this study, we analysed phenolic profiles of extra virgin olive oils (EVOOs) from different autochthonous cultivars from Croatia (Oblica, Bjelica, Buža, Žižolera) and investigated the biological effect of EVOO phenolic extracts (EVOO-PEs) on human cervical (HeLa) and human colon (SW48) cancer cell lines alone and in combination with cisplatin (cDDP), carboplatin (CBP), 5-fluorouracil (5-FU) and irinotecan. The quantitative evaluation of olive oil polyphenols was performed by HPLC-DAD and spectrophotometric analysis. The biological effect of EVOO-PEs alone and in combination with anticancer drugs was measured by MTT assay. Analysed EVOO-PEs differ in phenolic profile and inhibited HeLa and SW48 cells in a dose-dependent manner. Further, it is shown that EVOO-PEs (Oblica-Sea, Buža and Žižolera), in combination with anticancer drugs, increase the metabolic activity of HeLa and SW48 cells and have a protective role. These data imply careful consummation of olive oil during chemotherapy of cancer patients