imagine (Institute of molecular genetics and genetic engineering)
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Effect of enriched environment on serotonin and RNA editing of serotonin 2C receptor is specific for brain regions and mouse strains
Get PDFSerotonin neurotransmission is sensitive to environmental stimuli. Serotonin receptor
2C (HTR2C) undergoes dynamic A-to-I editing that fine-tunes cell response to
serotonin and is altered in depressed suicide victims and by pharmacological
treatments. We aimed to explore a mediating role of Htr2c mRNA editing in response
to enriched environment and factors involved in this response. Three-week-old
BALB/c and C57BL/6 male mice were housed in enriched and standard conditions for
four weeks. Htr2c mRNA editing pattern and expression, serotonin level and
expression of Adar and Adarb1 mRNAs (coding enzymes catalyzing A-to-I editing)
and Snord115 RNA (regulating Htr2c mRNA alternative splicing and editing) were
measured in prefrontal cortex (PFC) and hippocampus (HC), brain regions implicated
in suicidal behavior. BALB/c mice, a “stress-sensitive” strain due to genetically
determined lower serotonin level, responded to enriched conditions by adapting the
Htr2c editing pattern to a slight serotonin decrease in PFC and a significant increase
in HC. C57BL/6 mice, a “stress-resilient” strain, responded to enriched environment
by increasing the serotonin level and changing Adar and Adarb1 mRNAs expression
in HC, and without changes in PFC. Our findings suggest that the enriched
environment effect on the serotonin level and a mediating role of Htr2c mRNA
editing in PFC depend on the genetic background and its interactions with the
environment. On the other hand, changes in HC are primarily driven by enriched
environment.
Our results imply usefulness of enriched environment paradigm for understanding
interactions of genetic and environmental factors underlying suicidal behavior, which
might improve psychological treatments.BOOK OF ABSTRACTS: 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international participation 31 May – 2 June 2023. Belgrade, Serbi
Myositis-specific autoantibodies in a non-traveler, patient from a non-endemic country, with Plasmodium vivax malaria
Get PDFIntroduction: Autoantibodies (AAb) are a hallmark of immune-mediated inflammatory diseases. Malaria is a parasitic disease caused by Plasmodium protozoa. Individuals with malaria may present with a wide range of symptoms. It is frequently linked to the development of different AAb.Case description: A 35-year-old male presented with repeated episodes of fever, malaise, myalgia, dark urine, and yellowish sclera. Initial diagnostic workup revealed severe Coombs-positive anemia, increased C-reactive protein, and procalcitonin, pathological liver tests, high concentration of serum IgE, IgG, IgM, IgA, positive antinuclear antibodies (ANA), and positive antineutrophil cytoplasmatic antibodies (ANCA). In addition, myositis-specific antibodies directed to polymiositis-scleroderma 75 protein (PmScl75), threonyl-tRNA synthetase (PL-7), alanyl-tRNA synthetase (PL-12), Mi-2 antigen (Mi-2), Ku DNA helicase complex (Ku), signal recognition particle (SRP), and antiaminoacyl tRNA synthetase (EJ) were detected. The patient was suspected of having systemic lupus erythematosus and sent to the Clinic of Allergy and Immunology for further evaluation and treatment. A peripheral blood film examined by the hematologist during an episode of fever revealed intra-erythrocytic parasitic forms of Plasmodium vivax (P. vivax). After being diagnosed with P. vivax malaria, he was transferred to the Clinic for Infective and Tropical Diseases. The therapy consisted of artesunate/mefloquine and prednisone led to a complete clinical recovery and autoantibodies gradually disappeared.Conclusions: Malaria would not normally be considered during the initial diagnostic workup in a non-traveler and a patient from a non-endemic country. However, a thorough parasitic evaluation in patients presenting with a broad range of autoantibodies might be of particular importance
Enhanced enzymatic depolymerization of polylactic acid (PLA) through plasma pretreatment and subsequent conversion to biopolymer
No full textPolylactic acid (PLA) serves as a bio-based alternative to fossil-based single-use plastics, biodegrading at high temperatures (58°C) and humidity during industrial composting. Despite enzymes' ability to catalyze reactions at near-ambient temperatures, polymer rigidity can impede efficient depolymerization. To address these challenges, we conducted a study of enzymatic PLA degradation at 42°C combined with green plasma pretreatment to help disrupt the crystalline regions within the polymer. Here we report the effect of length of plasma pretreatment on the rate of PLA degradation by enzyme mix containing commercial enzymes with reported PLA degrading activity. Results indicate that a 5-minute plasma pretreatment significantly enhances enzymatic degradation, with a 16% weight loss achieved in 4 weeks—a two-fold increase compared to untreated PLA. Furthermore, we report the valorization of PLA into bacterial nanocellulose after enzymatic hydrolysis of the samples
The effects of deletion of the Mif gene on the development of obesity and hepatic steatosis in mice on fructose enriched diet
Get PDFHronična inflamacija niskog intenziteta ima važnu ulogu u patogenezi metaboličkih poremećaja, kao što
su gojaznost i dislipidemija, koji su često izazvani ishranom obogaćenom fruktozom i predstavljaju faktore
rizika za razvoj steatoze jetre i dijabetesa tipa 2. Faktor inhibicije migracije makrofaga (MIF) je plejotropni
citokin koji pored uloge u regulaciji imunskog odgovora može da reguliše metaboličke procese i oslobađanje
insulina iz pankreasa, međutim njegova uloga u metaboličkoj inflamaciji nije još uvek dovoljno razjašnjena.
Dodatno, pokazano je da se miševi sa deletiranim genom za Mif odlikuju izmenjenom osetljivošću
na insulin i glukozu. Stoga, fokus ovog rada je bio usmeren ka boljem razumevanju molekularnih mehanizama
metaboličkih efekata MIF-a, kao i ka rasvetljavanju kontroverzne uloge ovog citokina u ra-zvoju poremećaja
lipidnog metabolizma u jetri i visceralnom masnom tkivu miševa na režimu ishrane obogaćene
fruktozom.Chronic low-grade inflammation plays an important role in the development of metabolic disorders such
as obesity and dyslipidemia, which are often induced by a fructose-enriched diet and are risk factors for
the development of hepatic steatosis and type 2 diabetes. Macrophage migration inhibitory factor (MIF)
is a pleiotropic cytokine that, in addition to its role in regulating the immune response, can regulate metabolic
processes and the release of insulin from the pancreas; however, its role in metabolic inflammation
is not well understood. In addition, mice with a deleted Mif gene were found to have altered sensitivity to
insulin and glucose. Therefore, the focus of this work was to better understand the molecular mechanisms
of the metabolic effects of MIF and to elucidate the controversial role of this cytokine in the development
of dyslipidemia in the liver and visceral adipose tissue of mice on fructose-enriched diet
Beta-adrenergic receptors and kinases involved in the process of their downregulation in experimental model of cardiomyopathy induced by doxorubicin
Get PDFDoksorubicin je efikasan lek u terapiji brojnih maligniteta. Međutim, njegovu upotrebu umnogome ograničava
nastanak kardiotoksičnosti, koja može dovesti do kongestivne srčane insuficijencije. Mehanizmi
doksorubicinske kardiotoksičnosti nisu sasvim razjašnjeni, a kada dođe do kongestivne srčane insuficijencije,
stopa smrtnosti je približno 50%. Iako specifična terapija ne postoji, efikasnost su pokazali antagonisti
beta-adrenergičkih receptora (β-AR). U srčanoj insuficijenciji je pokazano da kompenzatorno
povećan tonus simpatikusa i cirkulišućih kateholamina dovodi do selektivne nishodne regulacije β1-AR,
što dalje smanjuje kontraktilnu snagu srca. U procesima desenzitizacije i nishodne regulacije β-AR, važnu
ulogu imaju kinaze G protein-spregnutih receptora (GRK) i arestini. Utvrđeno je da je GRK2 ushodno regulisana
u nekim eksperimentalnim modelima srčane insuficijencije i da njena inhibicija sprečava štetno
remodelovanje srčanog tkiva. Ovaj rad daje pregled rezultata istraživanja β-AR i procesa njihove nishodne
regulacije, kao i uticaja inhibicije GRK2 na remodelovanje srca u kardiomiopatiji izazvanoj doksorubicinom.Doxorubicin is an effective drug for the treatment of numerous malignancies. However, its use is greatly
hampered by the occurrence of cardiotoxicity, which can lead to congestive heart failure. The mechanisms
of doxorubicin cardiotoxicity are not fully understood, and when congestive heart failure occurs, the mortality
rate is approximately 50%. Although there is no specific treatment for doxorubicin cardiotoxicity,
beta-adrenergic receptor (β-AR) antagonists have limited efficacy. In heart failure, compensatory increased
sympathetic tone and circulating catecholamines lead to selective downregulation of β1-AR, which
further reduces the contractile force of the heart. G protein-coupled receptor kinases (GRKs) and arrestins
play an important role in the processes of desensitization and downregulation of β-AR. GRK2 has been
found to be up-regulated in some experimental models of heart failure and its inhibition prevents harmful
remodeling of cardiac tissue. This paper provides the findings on β-AR and the process of their downregulation,
as well as on the effects of GRK2 inhibition on cardiac remodeling in doxorubicin-induced
cardiomyopathy
An updated pharmacological insight into calotropin as a potential therapeutic agent in cancer
Get PDFCalotropin is a pharmacologically active compound isolated from milkweed plants like Calotropis procera, Calotropis gigantea, and Asclepias currasavica that belong to the Asclepiadaceae family. All of these plants are recognised as medical traditional plants used in Asian countries. Calotropin is identified as a highly potent cardenolide that has a similar chemical structure to cardiac glycosides (such as digoxin and digitoxin). During the last few years, cytotoxic and antitumor effects of cardenolides glycosides have been reported more frequently. Among cardenolides, calotropin is identified as the most promising agent. In this updated and comprehensive review, we aimed to analyze and discuss the specific mechanisms and molecular targets of calotropin in cancer treatment to open new perspectives for the adjuvant treatment of different types of cancer. The effects of calotropin on cancer have been extensively studied in preclinical pharmacological studies in vitro using cancer cell lines and in vivo in experimental animal models that have targeted antitumor mechanisms and anticancer signaling pathways. The analyzed information from the specialized literature was obtained from scientific databases until December 2022, mainly from PubMed/MedLine, Google Scholar, Scopus, Web of Science, and Science Direct databases using specific MeSH search terms. The results of our analysis demonstrate that calotropin can be a potential chemotherapeutic/chemopreventive adjunctive agent in cancer pharmacotherapeutic management
Mikrobiom-crevo-mozak osovina kod multiple skleroze
Get PDFThe microbiome-gut-brain axis (MGBA) represents a close two-way relationship between the gut and the central nervous system (CNS) mediated by the immune system, the enteric nervous system (ENS), the vagus nerve, and the gut microbiome. Gut microbes, including bacteria, fungi, and viruses, can communicate with the CNS and modulate the physiology of the brain in health and disease, which marks them as an important MGBA factor. It is becoming increasingly evident that gut microbiome dysbiosis is implicated in the onset and severity of different neurodegenerative and psychiatric diseases including multiple sclerosis (MS). MS is a chronic disease of the CNS associated with different genetic and environmental risk factors. Neuroinflammation and demyelination in the brain and the spinal cord are hallmark features of MS. The accumulating evidence shows that the MGBA, although a relatively new concept, has an important role in MS. Therefore, the purpose of this article is to review recent research on the gut-brain connection in MS, and to highlight MS-associated gut microbiota constituents and the role of bacterial metabolites in MS.Mikrobiom-crevo-mozak osovina (MGBA) predstavlja blisku dvosmernu vezu između creva i centralnog nervnog sistema (CNS) posredovanu imunskim sistemom, enteričnim nervnim sistemom (ENS), nervom vagusom i mikrobiomom creva. Posredstvom metabolita koje produkuju, mikroorganizmi creva, uključujući bakterije, gljive i viruse, komuniciraju sa CNS-om i tako utiču na funkcije mozga, zbog čega je mikrobiota creva prepoznata kao veoma važan faktor održavanja homeostaze MGBA. Takođe, veliki broj podataka ukazao je na povezanost disbioze mikrobioma creva i nastanka i težine simptoma različitih neurodegenerativnih i psihijatrijskih bolesti, uključujući multiplu sklerozu (MS), autoimunsku bolest nervnog sistema. MS je hronična bolest CNS-a povezana sa više genetskih faktora, kao i sa različitim sredinskim faktorima i životnim navikama. Najvažnija obeležja MS su neuroinflamacija i demijelinizacija u mozgu i kičmenoj moždini, a veliki broj istraživanja je ukazao i na specifične mikrobijalne markere ove bolesti. Cilj ovog rada je da pruži pregled najvažnijih podataka o povezanosti promena u sastavu i funkciji mikrobiote creva i patoloških promena karakterističnih za MS
Next-Generation Probiotics: health-promoting bacteria of the human gut
No full textIn recent years, a vast number of human diseases have been correlated with gut microbiota dysbiosis. The development of modern methods in molecular microbiology, such as the culturomics approach, as well as various multi-omics methods like next generation sequencing, transcriptomics and metabolomics analysis, coupled with large data sets correlation analysis, enabled the cultivation and characterization of novel anaerobic hitherto uncultivated Next-Generation Probiotics. In addition, the results of host-microbe interactions studies helped to reveal the mechanisms involved in the beneficial effects of Next-Generation Probiotics. Eventually, the obtained data on Next-Generation Probiotics will help to broaden the scientific knowledge on these bacteria, in terms of both their safety and health-promoting effects, unravel opportunities for the development of novel therapeutic strategies for prevention and treatment of tumors, metabolic, neuropsychiatric and other diseases, with the aim of relieving the symptoms of the diseases and increasing the quality of life for patients and their families. So far, the best characterized probiotics of the new generation are Akkermansia muciniphila, Faecalibacterium prauznitzii and Bacteroides fragilis.Poslednjih godina se veliki broj patoloških stanja i bolesti dovodi u vezu sa disbiozom crevne mikrobiote i promenama u njenom funkcionisanju. Razvoj savremenih metoda molekularne mikrobiologije, uključujući kulturomiku i integrativne pristupe kao što su sekvenciranje sledeće generacije, transkriptomska analiza dualne RNK sekvence i analiza metabolomike, omogućio je identifikaciju, kultivaciju i karakterizaciju novih anaerobnih, do sada nekultivisanih probiotika, nazvanih probiotici sledeće generacije. Pored toga, rezultati in vitro i in vivostudija proučavanja interakcija domaćina sa mikrobiotom pomogli su u rasvetljavanju mehanizama delovanja probiotika sledeće generacije. Na kraju, dobijeni podaci o probioticima sledeće generacije pomoći će da se prošire naučna saznanja o ovim bakterijama, kako u pogledu njihove bezbednosti, tako i u pogledu njihovog uticaja na zdravlje, otvarajući mogućnost za nove terapijske pristupe u prevenciji i terapiji metaboličkih bolesti, tumora, neurodegenerativnih i psihijatrijskih bolesti i drugih bolesti, u cilju ublažavanja simptoma bolesti i poboljšanja kvaliteta života pacijenata i njihovih porodica. Do sada najbolje opisani probiotici sledeće generacije su Akkermansia muciniphila, Fecalibacterium prauznitzii i Bacteroides fragili
Effect of single-generation domestication of pikeperch on the performance of the offspring in conventional and pond recirculation aquaculture system
Get PDFPikeperch aquaculture technologies have significantly improved, yet knowledge regarding the adaptation of pikeperch to captivity is very scarce. This study aimed to evaluate the survival, growth, stress response, and immune system function of the F2 generation of pikeperch subjected to pond nursing – Recirculating Aquaculture System (RAS) dry feed adaptation, with either RAS or pond grow-out. F2 generation in this research originated from the broodstock reared in the pond system during grow-out, while F1 originated from wild breeders. Critical points in fish growth were analyzed, including transport of pond-nursed juveniles to RAS at 42 DPH, dry feed habituation (42–52 DPH) and post-habituation (52–64 DPH) phase, as well as the on-grow/grow-out (64–154 DPH) phase. Our results showed better growth and survival of the F2 generation in comparison to F1 in pond grow-out. However, the F1 generation was superior in conventional RAS grow-out. Nevertheless, during RAS dry feed habituation, F1 fish were inferior, both in terms of growth and survival, in comparison to F2 fish. Stress and immunological marker analysis revealed higher stress sensitivity, accompanied by stronger immune system activation, in F2 generation in comparison to F1. This was manifested as higher cortisol and immunoglobulin response after moving fish from one system to another. Hypothetically, stronger stress and immune response might have induced better dry feed adaptation during the habituation phase in RAS, and better control of microbial growth in the grow-out environment with a higher microbial load, such as pond. On the other hand, according to the same hypothesis, in a cleaner grow-out environment such as RAS, fish with a weaker cortisol and immunological response would be at an advantage, since these fish are expected to have a richer intestinal microbiota that would eventually support better food digestion and growth. Assumed selection points shaping pikeperch response to farming have been discussed.The authors would like to thank David Koljukaj (https://www.linkedin.com/in/david-koljukaj/?original Subdomain=rs), an English speaker, holding the Common European Framework of Reference for Languages: Learning, Teaching, Assessment (CEFR) C2 certificate (issued by the Council of Europe), for proofreading the manuscript.Related to raw data: [https://imagine.imgge.bg.ac.rs/handle/123456789/2070
Supplementary data for the article: Obradović, M., Malešević, M., Di Luca, M., Kekić, D., Gajić, I., McAuliffe, O., Neve, H., Stanisavljević, N., Vukotić, G.,& Kojić, M.. (2023). Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae. in Viruses, 15(3), 628. https://doi.org/10.3390/v15030628
Get PDFSupplementary material for:[https://doi.org/10.3390/v15030628]Related to published version:[https://imagine.imgge.bg.ac.rs/handle/123456789/2065