imagine (Institute of molecular genetics and genetic engineering)
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Biological effect of pomegranate polyphenols on the components of metabolic syndrome: implications on oxidative stress
Get PDFNar (Punica granatum, L) je jedan od najstarijih jestivih plodova koji se koristi u prevenciji i lečenju od davnina.
Različiti delovi biljke, kao što su plod, seme, kora i lišće, sadrže bioaktivne sastojke za koje se navodi da poseduju
lekovita i terapeutska svojstva. Međumnogobrojnimbioaktivnimkomponentama u naru, polifenoli
predstavljaju najvažniju grupumolekula sa pozitivnimefektomna zdravlje. Hipoglikemijski, hipolipemijski,
hipotenzivni i anti-oksidativni efekat polifenola nara potvrđen je u brojnimstudijama. Ovaj pregledni rad ima
za cilj da predstavi najnovija istraživanja o strukturi i biološkoj aktivnosti komponenata nara i njihovompotencijalnom
korisnom efektu u terapiji bolesti povezanih sa metaboličkim sindromom.Pomegranate (Punica granatum, L) is one of the oldest edible fruits used in prevention and treatment. Various
parts of the plant, such as fruit, seeds, bark, and leaves, contain bioactive ingredients that possess medicinal
and therapeutic properties. Among the many bioactive components in pomegranate, polyphenols
are the most important group of molecules with a positive effect on health. The hypoglycemic, hypolipidemic,
hypotensive, and anti-oxidative effects of pomegranate polyphenols have been confirmed in numerous
studies. The aim of this review is to present the latest research on the structure and activity of
bioactive components of pomegranate and their potential beneficial effect in the treatment of diseases related
to metabolic syndrome
Regulation of proteolysis of intrinsically disordered proteins: physiological consequences
No full textProteolysis represents a primary recycling system for amino acids.
Moreover, by controlling the protein turnover, proteolysis plays an
important role in key cellular processes such as control of cell cycle,
programmed cell death (including senescence) and response to various
stimuli. In eukaryotic cells, most proteins are degraded by autophagy and
26S proteasome machinery, composed in general of 20S proteolytic core and 19S regulatory particle. The protein susceptibility to proteolysis is
determined by its structural features. Folded globular proteins in their
native state are rarely degraded, however when misfolded, denatured or
when an unstructured region is attached, the degradation is promoted.
Proteins natively containing intrinsically disordered regions (IDRs) or
completely lacking the stable secondary and tertiary structures are
defined as intrinsically disordered proteins (IDPs). Due to their high
intramolecular flexibility and plasticity, IDPs are involved in DNA
metabolism, transcriptional activation, autophagy, and signalling
cascades related to response to various stimuli. In sessile organisms such
as plants, IDPs enable prompt acclimation to external factors, including
light perception, adaptation to oxidative stress and water loss, and
regulation of protective, antioxidative and secondary metabolism.
Binding of specific ligands and partners to particular IDP triggers
structural changes and affects the stability of IDP, its susceptibility to
proteolysis and aggregation-propensity. Theabnormal aggregation of
several IDPs and altered proteolysis pathways are closely connected with
serious neurodegenerative disorders, such as Alzheimer’s and Parkinson's
diseases. In this chapter, we discuss the current understanding of
proteolytic processes of specific, well-characterised IDPs under different
physiological states, emphasizing the influence of the microenvironment
and ligands/partners on their conformation.This is a Chapter
Characterization of zebrafish ankrd1a, ankrd1b and ankrd2 genes in development and stress response
Get PDFU popriječno-prugastim mišićima članovi familije mišićnih proteina sa ankirinskim ponovcima (eng. Muscle Ankyrin Repeat Proteins, MARP) učestvuju u mehanotransdukciji signala sa sarkomere u jedro, gdje modulišu ekspresiju ciljnih gena. Eksprimirani su tokom razvića srca i skeletnih mišića, povećanog mehaničkog opterećenja ovih organa i u patološkim stanjima poput infarkta miokarda i miopatija. Smatra se da ovi proteini imaju ulogu u adaptaciji mišićne ćelije na stres, ali je ona i dalje nedovoljno istražena. Kako bi upotpunili znanje o MARP familiji, njeni članovi proučavani su u zebrici, model organizmu naročito pogodnom za in vivo analizu razvića, genetičke manipulacije i proučavanje mehanizama regeneracije. Ekspresija ortologa MARP gena zebrice (ankrd1a, ankrd1b i ankrd2) analizirana je tokom razvića i u odgovoru na dvije vrste stresa: povećanu fizičku aktivnost i povredu srca. Generisanje mutanata za MARP gene omogućilo je njihovu funkcionalnu analizu u ovim procesima. Određen je profil ekspresije MARP gena tokom razvića zebrice, od embriona do adulta, a reporterska linija TgBAC(ankrd1a:EGFP) pružila je uvid u ekspresiju ankrd1a sa visokom rezolucijom. Povećana fizička aktivnost indukovala je ekspresiju MARP gena u srcu i skeletnim mišićima zebrice. Ekspresija ankrd1a je povećana u kardiomiocitima graničnog regiona povrede i zavisna od stadijuma remodelovanja miokarda u regenerišućem srcu. Iako mutacije u MARP genima nisu dovele do očigledne promjene fenotipa, kod adultnih jedinki zebrice genotipa ankrd1a-/- primjećena je smanjena proliferacija kardiomiocita nakon povrede srca, ali bez uticaja na konačni ishod regeneracije. Ovim istraživanjem napravljen je ključni korak ka uspostavljanju zebrice kao model ogranizma za proučavanje funkcije članova MARP familije.Members of the muscle ankyrin repeat protein (MARP) family in striated muscles play a role in mechanotransduction of signals from the sarcomere to the nucleus, where they modulate expression of target genes. MARPs are expressed during heart and skeletal muscle development, increased mechanical load and in pathological conditions such as myocardial infarction and myopathies. Their presumed role in muscle adaptation to stress remains poorly understood. To extend our knowledge of the MARP family members, they were studied in the zebrafish, a model organism well suited for developmental and regeneration studies, as well as genetic manipulations. Expression of zebrafish MARP gene orthologues (ankrd1a, ankrd1b, ankrd2) was analysed during development and in response to two types of stress: increased physical activity and cardiac injury. Introduction of mutations in the MARP family genes allowed for functional analysis of its members in these processes. Expression profile of MARP genes during zebrafish development was determined in stages from embryo to adult, while the transgenic reporter line TgBAC(ankrd1a:EGFP) provided tracking of ankrd1a expression with higher resolution. Increased physical activity induced the expression of MARP genes in zebrafish heart and skeletal muscles. Expression of ankrd1a was found increased in the injury border zone cardiomyocytes and dependent on myocardium remodelling stage in the regenerating heart. Although mutations in MARP genes did not cause phenotype alterations, a lower rate of cardiomyocytes proliferation was observed in ankrd1a-/- zebrafish following cardiac injury, but with no effect on the regeneration outcome. This study is a key step towards establishing the zebrafish as a model organism for functional studies of the MARP family
Biotransformation of Perrottetin F by Aspergillus niger: New Bioactive Secondary Metabolites
Get PDFBiotransformation of bis-bibenzyl perrottetin F (1), isolated from the liverwort Lunularia cruciata by Aspergillus niger, has been investigated. New metabolites (2-4) have been isolated using reversed phase semipreparative HPLC and their structures were established to be 8-hydroxyperrottetin F, C-7-C-8 cleaved product, and perrottetin F 6'-sulfate using 1D and 2D NMR, HR-ESI-MS, IR and UV spectroscopy. The antimicrobial and cytotoxic properties of these compounds were also evaluated. Given the suggested cytotoxic properties of the parent compound, antiproliferative activity against healthy human lung fibroblasts (MRC5) and human lung carcinoma (A549) of three metabolites were evaluated revealing their lower cytotoxic properties in comparison to the starting compound - perrottetin F. The antimicrobial properties of these compounds were also evaluated, with the inhibitory activity against the Pseudomonas aeruginosa PAO1 and Staphylococcus aureus determined between 100 mu M and 450 mu M. The metabolites showed remarkable ability to inhibit synthesis of bacterial quorum-sensing signal molecules such as short chain acyl homoserine lactones (AHLs). Therefore, biotransformation method represents fast and effective tool for obtaining new bioactive structures
Structural Characterization, Antimicrobial Activity and BSA/DNA Binding Affinity of New Silver(I) Complexes with Thianthrene and 1,8-Naphthyridine
Get PDFThree new silver(I) complexes [Ag(NO3)(tia)(H2O)](n) (Ag1), [Ag(CF3SO3)(1,8-naph)](n) (Ag2) and [Ag-2(1,8-naph)(2)(H2O)(1.2)](PF6)(2) (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56-7.81 mu g/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1-3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids
Facile Synthesis of L-Cysteine Functionalized Graphene Quantum Dots as a Bioimaging and Photosensitive Agent
Get PDFNowadays, a larger number of aggressive and corrosive chemical reagents as well as toxic solvents are used to achieve structural modification and cleaning of the final products. These lead to the production of residual, waste chemicals, which are often reactive, cancerogenic, and toxic to the environment. This study shows a new approach to the modification of graphene quantum dots (GQDs) using gamma irradiation where the usage of reagents was avoided. We achieved the incorporation of S and N atoms in the GQD structure by selecting an aqueous solution of L-cysteine as an irradiation medium. GQDs were exposed to gamma-irradiation at doses of 25, 50 and 200 kGy. After irradiation, the optical, structural, and morphological properties, as well as the possibility of their use as an agent in bioimaging and photodynamic therapy, were studied. We measured an enhanced quantum yield of photoluminescence with the highest dose of 25 kGy (21.60%). Both S- and N-functional groups were detected in all gamma-irradiated GQDs: amino, amide, thiol, and thione. Spin trap electron paramagnetic resonance showed that GQDs irradiated with 25 kGy can generate singlet oxygen upon illumination. Bioimaging on HeLa cells showed the best visibility for cells treated with GQDs irradiated with 25 kGy, while cytotoxicity was not detected after treatment of HeLa cells with gamma-irradiated GQDs
Physical activity and exercise as an essential medical strategy for the COVID-19 pandemic and beyond
No full textCOVID-19 disease has been a problem in today's society, which has worldwide effects on different areas, especially on the economy; also, from a health perspective, the disease affects the daily life quality. Physical activity is one major positive factor with regard to enhancing life quality, as it can improve the whole psychological, social, and physical health conditions. Current measures such as social distancing are focused on preventing the viral spread. However, the consequences on other areas are yet to be investigated. Elderly, people with chronic diseases, obese, and others benefit largely from exercise from the perspective of improved health, and preventive measures can drastically improve daily living. In this article, we elaborate the effects of exercise on the immune system and the possible strategies that can be implemented toward greater preventive potential
The large plasmidome of Lactococcus lactis subsp. lactis by. diacetylactis S50 confers its biotechnological properties
No full textPlasmids are autonomous episomally replicating genetic elements, which carry backbone genes important for the replication and maintenance within their host, and accessory genes that might confer an advantage to their host under specific selective pressure in its ecological niche. The genome of dairy isolate L. lactis subsp. lactis by. diacetylactis S50 was sequenced using the PacBio SMRT Cell Seq-RSII platform and revealed to possess one of the largest plasmidomes among L. lactis strains studied so far, harboring six plasmids: pS6 (5553 bp), pS7a (7308 bp), pS7b (7266 bp), pS19 (19,027 bp), pS74 (74,256 bp) and pS127 (127,002 bp) in total representing 8.9% of genome size (240,412 bp). Based on predicted plasmid replication proteins and origins it appears that all six plasmids replicate via the theta-type mechanism. The two the largest plasmids (pS74 and pS127), carry a number of genes known to be important for growth and survival in the dairy environment. These genes encode technological functions such as bacteriocin production, protein degradation, magnesium and cobalt/nickel transporters, selenium binding, exopolysaccharides (EPS) production, bacteriophage and stress resistance. Beside genes for replication, the small plasmids (pS6, pS7a, pS7a, and pS19) also carry genes important for mobilization and host survival such as type I restriction-modification (R-M) system, metal transporters, enzymes and transcriptional regulators. All plasmids in S50 strain are mobilizable, containing an oriT sequences, while pS127 is self-conjugative and allows for mobilization of the other plasmids. Small plasmids are prone to structural and segregational instability, while pS127 appeared to be segregationally stable thanks to the possession of two partition systems. The main characteristic of plasmid p574 is EPS production, while plasmid p5127 is characterized by proteinase and multiple bacteriocins, tra locus, phage abortive systems and metal transporters. In addition to LcnA and LcnB, plasmid p5127 encodes several bacteriocin-pheromone molecules and a new bacteriocin named LcnS50, with narrow spectrum of action limited to lactococci, that has been successfully cloned and heterologously expressed
Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of Acinetobacter baumannii by Inhibiting ompA Gene Expression
No full textAn increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2 '-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.Conference poster: [https://imagine.imgge.bg.ac.rs/handle/123456789/2820]Peer-reviewed manuscript:[https://imagine.imgge.bg.ac.rs/handle/123456789/2821]Supporting information:[https://imagine.imgge.bg.ac.rs/handle/123456789/2822
Twenty different late embryogenesis abundant proteins (LEAPs) accumulate in desiccated Ramonda serbica leaves
Get PDFResurrection plant Ramonda serbica Panc. survives desiccation for a long period and fully recovers metabolic functions already within one day upon watering [1]. Besides osmotic stress, desiccation provokes the accelerated generation of reactive oxygen species. The aim of our study was obtaining more insight into the mechanisms of desiccation tolerance in R. serbica by TMT labelled comparative quantitative proteomics of hydrated (HL) and desiccated leaves (DL). After de novo transcriptome analysis, 189456 transcripts with 189003 unigenes were annotated with seven common databases. Proteomic analysis allowed for the relative quantification of 895 different protein groups, 321 with a statistically significant difference in abundance between FL and DL. Among them, 25% referred to chloroplast and almost the same percentage were associated with desiccation and oxidative stress. Almost all differentially abundant proteins related to photosynthetic processes were down-regulated in DL, while those required for protein translation were more abundant in HL. Within differentially abundant proteins involved in antioxidative defence, the levels of enzymes involved in ascorbate-glutathione cycle, peroxiredoxins, Fe and Mn superoxide dismutase (SOD) were all reduced in DL, while germin-like proteins, three Cu/Zn SOD isoforms and polyphenol oxidases were more abundant in DL compared with HL. The protein family with the highest number of members showing the greatest accumulation upon desiccation comprised twenty different late embryogenesis abundant proteins (LEAPs), similarly as found by differential transcriptomic analysis. Taken together, our results imply a key role of LEAPs and Cu/Zn SOD in protective mechanism against desiccation in R. serbica, that may have significant implications on drought-related studies of crops grown in arid areas. This work was supported by the Science Fund of the Republic of Serbia (PROMIS project LEAPSyn-SCI, grant number 6039663). M.V. wishes to acknowledge the support of COST Action BM1405 for approving STSM in Padua during 2017 and 2018.Poster: [https://imagine.imgge.bg.ac.rs/handle/123456789/1857