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Effect of continuous in-utero exposure to ELF-MF (50 Hz, 0.5 mT) on liver function in peripubertal rats
No full textObjectives: An extremely low-frequency magnetic field (ELF-MF) generated by domestic
installations, household appliances, and power grids could have various adverse health effects [1].
Previously, subchronic exposure of adult male rats to ELF-MF (0.02 mT, 0.1 mT, and 0.5 mT) for 2
hours daily for 4 weeks did not produce any biochemical changes in the blood associated with liver
health [2]. However, there is scarce information on whether continuous in-utero exposure to ELF
MF affects liver function. This study fills the gap and addresses the effect of continuous in-utero
exposure to ELF-MF (50 Hz, 0.5 mT) on blood levels of albumin, alkaline phosphatase (ALP),
alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase
(GGT) and bilirubin in peripubertal age.
Methods: Adult male and female rats (Wistar IGS) were placed near the on/off
electromagnet generating ELF-MF (50 Hz, 0.5 mT) until conception and the pregnant females
thereafter until the offspring were born. Immediately after birth, the mothers and their offspring
were removed from the ELF-MF exposure system. Blood was collected from the trunk of each
animal between 09:00 and 10:00 in the morning, and the sera were isolated and stored at -80°C
until analysis. Serum parameters of liver function were analyzed using an automated biochemical
analyzer (BS-240 Vet). The Kruskal–Wallis and Mann-Whitney tests were used to evaluate the
changes in each parameter.
Results: Continuous in-utero exposure to ELF-MF causes the following significant effects
in peripubertal offspring: (1) Decreased albumin concentration in males, (2) Increased ALT, AST,
and GGT in males and decreased ALT, AST, and GGT in females, and (3) Decreased bilirubin
concentration in both sexes.
Conclusion: These results suggest that continuous in-utero exposure to ELF-MF alters
liver function at peripubertal age. References:
1.
Klimek, A., & Rogalska, J.. Brain Sciences, 2021, 11, 2, 174.
2. Luo, X., et al., Toxicology and Industrial Health, 2017, 33(4), 365-372.Ristić GS, editor. Book of Abstracts: Thirteenth International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2025; 2025 Jun 16-20; Herceg Novi, Montenegro. Niš, Serbia: RAD Centre; 2025. p. 33
Physiological and Oxidative Stress in General and Spinal Anesthesia for Elective Cesarean Section in Women: Is There Any Difference?
No full textThis study evaluates the influence of general anesthesia (GA) and spinal anesthesia (SA) on physiological and oxidative stress in parturients undergoing elective cesarean section, one of the most frequently performed surgical procedures worldwide. A total of 101 pregnant women were included, categorized into GA (n = 51) and SA (n = 50) groups. Blood samples were collected at three time points: one hour before surgery (Measurement 1), at umbilical cord clamping (Measurement 2), and two hours post-surgery (Measurement 3). Biomarkers of oxidative stress, complete blood count, and levels of biochemical parameters were measured. In second and/or third measurement, biochemical blood analysis showed increased prolactin and cortisol levels, followed by spike of glucose and insulin in the GA group. However, levels of tri-iodothyronine were reduced in both groups in the third measurement. Glutathione S-transferase (GST) activity was increased in both groups in third measurement. The results showed increased concentrations of total SH groups and decreased concentrations of non-protein SH groups in the GA group during Measurement 2. Lymphocyte count was found to be predictor of GST levels. The results indicate more a pronounced endocrine response in GA group and speak in favor of spinal anesthesia. Both kinds of anesthesia are equally safe in terms of the oxidative status of the tissue
Activity of a platinum(IV)–flurbiprofen conjugate free and immobilized into mesoporous nanostructured silica on colon cancer
No full textIntroduction. Prostaglandin E2 (PGE2), a main mediator of inflammation, is a product of cyclooxygenase-2 (COX-2) activation, whose expression is increased in human colorectal cancer. In addition to its role in inflammation, PGE2 also acts as a mitogenic signaling molecule released by dying tumor cells and is thus involved in the repopulation of tumors. To improve the effect of chemotherapy by elimination of the mitogenic signal mediated by PGE2, a drug with cisplatin core – platinum(IV) complex was synthesized bearing the anti-inflammatory drug flurbiprofen. Additionally, the conjugate was immobilized into mesoporous silica nanostructural material SBA-15 in order to enable improved delivery of the drug into tumor tissue. The cytotoxicity was assessed in 2D and 3D culture system, as well in vivo using a syngeneic mouse model of colon cancer. Material and method. The potential cytotoxicity of free and immobilized platinum(IV)-flurbiprofen conjugate was determined in murine cell lines 4T1, B16, CT26, and MC38 using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet as viability assays. Organoids were established from MC38-induced tumors in C57BL/6 mice which were then isolated, digested and further propagated. A CellTiter-Glo™ luminescent cell viability assay was employed to evaluate the antitumor effect of the drugs on organoids. The in vivo efficacy of the drugs was investigated in tumor-bearing C57BL/6 mice. Result and discussion. All tumor cell lines showed a dose-dependent decrease in viability after treatment with the drug conjugate and the corresponding SBA-15 formulation. MC38 cells were selected for further studies as they proved to be very sensitive to the applied treatments. Colon cancer organoids, which better simulate the architecture of tumor tissue than 2D cultures, showed a remarkable decrease in viability after 6 days of treatment with both drug formulations, while IC50 values were approximately several times higher than those obtained in 2D cultures. Finally, administration of both the drug conjugate and the corresponding nanostructured material to tumor-bearing C57BL/6 mice in a therapeutic regimen resulted in a statistically significant reduction in tumor volume compared to the control group. Conclusion. The strong antitumor potential of the platinum(IV)- flurbiprofen conjugate free and immobilized into SBA-15 in a model of mice colon cancer opens up many opportunities for further research.EACR 2025 Congress: Innovative Cancer Science; 2025 Jun 16-19; Lisbon, Portugal. John Wiley and Sons; 2025. p. 748-9. (Molecular Oncology; Vol. 19; Suppl. 1)
Expression of components involved in cholesterol homeostasis maintenance during experimental autoimmune encephalomyelitis in rat spinal cord
No full textDysregulations in cholesterol homeostasis contribute to the pathogenesis of multiple sclerosis (MS) and its best described animal model, experimental autoimmune encephalomyelitis (EAE). Cholesterol is an important component of myelin, which is necessary for signal transmission between neurons. Demyelination leads to the formation of oxysterols, degradation products of cholesterol that are ligands for nuclear liver X receptors (LXRs). Genes regulated by LXRs are involved in cholesterol efflux, absorption, transport, and excretion, which we investigated in this study. In this study, we detected changes in gene expression of Srebf1, Ldlr, Soat1, Abca1, Lrp1, and Npc1, all of which are important in the regulation of cholesterol homeostasis, during the course of EAE in male and female rats. In particular, differential expression of Srebf1, Ldlr, and Soat1 was observed in the spinal cord of male and female rats during EAE. Moreover, these genes are altered during EAE. In contrast, the expression of Abca1 and Lrp1 was significantly affected only by sex. In male animals, the expression of Npc1 is conspicuously reduced in EAE pathology.
Thus, our study confirms the involvement of enzymes of cholesterol metabolism in the pathophysiology of EAE, with sex and disease progression affecting the expression of these genes. These findings may improve the understanding of neurodegenerative diseases associated with impaired lipid metabolism in the brain, such as MS/EAE
Final report for the “Experimental evolutionary approach in the development of insect control methods - ELEVATE” project no. 7683961: Dec. 2021 - Jan. 2025
No full textInsect pests pose a significant threat to agricultural sustainability. Conventional pest management strategies often rely on insecticides, which provide temporary relief but are associated with environmental harm, non-target species impact, and the evolution of resistance in target pests. The ELEVATE project employed experimental evolution to track diverse phenotypic and genomic changes across generations and experimental conditions. Project results are offering insights into key mechanisms driving resistance to insecticides, ability of insects to expand host range, and the development of novel, environmentally sustainable pest control methods (Trojan Female Technique). The ELEVATE project integrated three aspects of pest control using experimental evolution in order to: 1) understand the evolution of insecticide resistance through phenotypic and morphological analyses, 2) evaluate life-history plasticity and population dynamics during host shifts to predict potential damage to stored products, and 3) develop a novel pest control method targeting natural mitochondrial mutations to reduce male-specific reproductive output
Attention-deficit/hyperactivity disorder-related psychomotor activity and altered neuronal activity in the medial prefrontal cortex and striatum in the A53T mouse model of Parkinson's disease and other synucleinopathies: Findings from an “endophenotype” approach
No full textAttention-Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of Parkinson's disease (PD) and other synucleinopathies later in life. The severity of the ADHD phenotype may play a significant role in this association. There is no indication that any of the existing animal models can unify these disorders. Using the Open Field Test, amphetamine-challenge test, Western blot and immunohistochemical analysis of neuronal activity markers (c-Fos, FosB and ΔFosB) we performed a deliberate neurobehavioral characterization of 6-month-old hemizygous A53T carriers (A53T+) of the JAX006823 strain, evaluating the utility of this transgenic mouse model of PD and other synucleinopathies in ADHD/PD continuum research. Adhering to the “endophenotype” approach, non-transgenic littermates (A53T-) and C57BL/6J mice (used to maintain the colony) were examined with A53T+ mice, to differentiate between biomarkers of transgenicity and endophenotypic traits related to the genetic background of the strain. Obtained results revealed that increased behavioral and acute striatal response to novelty, increased basal neuronal activity of the ventromedial prefrontal cortex and rate-dependent calming effect of amphetamine were endophenotypic characteristics of the strain. Increased acute response of the medial prefrontal cortex to novelty and chronic increase in neuronal activity of the striatum appeared as the mark of transgenicity. To the best of our knowledge, this is the first study to indicate external validity of a transgenic mouse model of PD and other synucleinopathies with the neurobehavioral pathology associated with ADHD, hinting at its potential in preclinical research of ADHD/PD continuum. The full capacity of the model remains to be explored
Fauna dnevnih leptira (Lepidoptera: Papilionoidea Latreille, [1802]) Kosova i Metohije, Republika Srbija: Faunističko–ekološka studija
No full textDoes mercury affect morphology, developmental stability and canalization of the skull in the Common wall lizard (Podarcis muralis)?
No full textEnvironmental pollution by metals and metalloids can have a detrimental effect on the fitness and development of organisms. Studies on the influence of metals and metalloids as environmental stressors on developmentally and functionally complex morphological structures of reptiles are important, as this group of vertebrates is highly threatened and is an important component of food webs. To assess the effects of chronic mercury exposure on cranium morphology and post-natal development in a model species of lizards, we analysed the concentration of this metal in liver tissues in the population of the Common wall lizard (Podarcis muralis) from the mercury mine tailings and the control population, and possible differences in skull size, shape, developmental stability and canalization between the two groups. Patterns of variation and asymmetry of the cranium shape were analysed using geometric morphometrics. The mercury concentration was significantly higher in the population from the polluted locality, but had very little to no effect on the cranial morphology. Juveniles and females from both sites had the same size and shape of the dorsal and ventral cranium, while males showed small differences in ventral cranium shape, reflected in slightly longer maxillae and wider crania at the polluted site. The pattern of sexual dimorphism remained constant at both localities. Both static and ontogenetic allometry were significant in both groups, and allometric trajectories did not differ between the two sites. The differences in fluctuating asymmetry (FA) between localities were not statistically significant for the dorsal and ventral cranium. The results do not support the idea that FA can be used as an early indicator mercury exposure at the population level
Профил карденолидних гликозида код изабраних врста рода Digitalis
No full textВрсте рода Digitalis представљају значајан природни извор биоактивних карденолидних гликозида са широком применом у терапији срчаних обољења. Циљ овог истраживања био је да се испита утицај биљне врсте и екстракционих услова на профил и
концентрацију карденолида код четири самоникле врсте рода Digitalis са подручја
Србије: Digitalis lanata, D. grandiflora, D. ferruginea и D. laevigata. Квантитативном
хемијском анализом идентификован је широк спeктар једињења укључујући шећере,
фенолна једињења, карденолиде, сапонине, масне и органске киселине. Дигиталин је
детектован код свих испитиваних врста, са највишом концентрацијом у D. lanata, док
је најнижа вредност утврђена код D. laevigata. Дигоксин је идентификован код три од
четири врсте, изузев D. laevigata, док је десланозид у значајној концентрацији детектован искључиво код D. lanata. Ланатозид Ц је доминантан карденолид детектован код
врсте D. lanata, док је дигоксигенин ди-деоксихексозид најзаступљеније једињење у
узорцима D. grandiflora. Тигонин је најефикасније екстрахован применом повишене
температуре у узорцима D. ferruginea. Међу фуростанолним гликозидима, гликозид 1
је карактеристичан за врсту D. lanata, док су гликозиди 2 и 3 доминантни код D. laevigata. Екстракција апсолутним етанолом показала се као најефикаснија за изоловање
карденолида попут дигиталина, дигоксигенин ди-деоксихексозида и ланатозида Ц,
док је употреба воде била најпогоднија за екстракцију дигоксина. Резултати указују
на значајне међуврсне разлике у профилу карденолида, при чему се D. lanata издваја
као најбогатији и најперспективнији извор ових фармаколошки релевантних једињења.
Присуство диоксигенинских деривата у D. grandiflora сугерише на могућност коришћења ове врсте као алтернативног извора ове групе карденолида.Vrste roda Digitalis predstavljaju značajan prirodni izvor bioaktivnih kardenolidnih glikozida sa širokom primenom u terapiji srčanih oboljenja. Cilj ovog istraživanja bio je da se ispita uticaj biljne vrste i ekstrakcionih uslova na profil i koncentraciju kardenolida kod četiri samonikle vrste roda Digitalis sa područja Srbije: Digitalis lanata, D. grandiflora, D. ferruginea i D. laevigata. Kvantitativnom hemijskom analizom identifikovan je širok spektar jedinjenja uključujući šećere, fenolna jedinjenja, kardenolide, saponine, masne i organske kiseline. Digitalin je detektovan kod svih ispitivanih vrsta, sa najvišom koncentracijom u D. lanata, dok je najniža vrednost utvrđena kod D. laevigata. Digoksin je identifikovan kod tri od četiri vrste, izuzev D. laevigata, dok je deslanozid u značajnoj koncentraciji detektovan isključivo kod D. lanata. Lanatozid C je dominantan kardenolid detektovan kod vrste D. lanata, dok je digoksigenin di-deoksiheksozid najzastupljenije jedinjenje u uzorcima D. grandiflora. Tigonin je najeefikasnije ekstrahovan primenom povišene temperature u uzorcima D. ferruginea. Među furostanolnim glikozidima, glikozid 1 je karakterističan za vrstu D. lanata, dok su glikozidi 2 i 3 dominantni kod D. laevigata. Ekstrakcija apsolutnim etanolom pokazala se kao najeefikasnija za izolovanje kardenolida poput digitalina, digoksigenin di-deoksiheksozida i lanatozida C, dok je upotreba vode bila najpogodnija za ekstrakciju digoksina. Rezultati ukazuju na značajne međuvrsne razlike u profilu kardenolida, pri čemu se D. lanata izdvaja kao najbogatiji i najperspektivniji izvor ovih farmakološki relevantnih jedinjenja. Prisutvo digoksigeninskih derivata u D. grandiflora sugeriše mogućnost korišćenja ove vrste kao alternativnog izvora ove grupe kardenolida.Stanković M, Bojović B, Stefanović O, Kosanić M, Milutinović M, editors. Program i izvodi saopštenja: Druga konferencija srpskog biološkog društva "Stevan Jakovljević" Kragujevac; 2025 Sep 17-19; Kragujevac, Serbia. Kragujevac: Srpsko biološko društvo "Stavan Jakovljević"; 2025. p. 99
Phenotypic plasticity of the yellow-bellied toad (Bombina variegata) under habitat drying conditions
No full textEkološki uslovi u prirodi su promenljivi, pa organizmi moraju biti sposobni da se prilagode tim promenama kako bi opstali. Sposobnost jednog genotipa da u odgovoru na promene sredine modifikuje razviće, osobine životne istorije, morfologiju i ponašanje naziva se fenotipska plastičnost.
Isušivanje staništa predstavlja jedan od najsnažnijih abiotičkih stresora koji remeti životni ciklus vodozemaca. Mnoge vrste bezrepih vodozemaca imaju sposobnost da ubrzaju razviće i završe metamorfozu pre nego što stanište presuši. U ovoj disertaciji ispitali smo kako isušujući uslovi staništa utiču na osobine životne istorije, morfologiju i fiziologiju žutotrbog mukača (Bombina variegata). Rezultati su pokazali da ispitana populacija nema sposobnost da ubrza razviće u isušujućim uslovima. Naprotiv, larvalni period je bio produžen ili nepromenjen, nezavisno od stadijuma razvića u kom su jedinke bile izložene isušivanju. Isušujući uslovi su negativno uticali na dužinu tela i masu jedinki, što se negativno odrazilo na stopu rasta i kondicioni indeks, na početku (GS 42) i na kraju metamorfoze (GS 46). Međutim, to se nije odrazilo na dužinu i oblik repa niti na skakačke performanse juvenilnih jedinki. Takođe, nisu zabeležene promene u nivou kortikosterona ni u parametrima antioksidacionog sistema.
Nepromenjen ili produžen larvalni period u uslovima isušivanja, uz stabilne fiziološke parametre, ukazuju na moguću modifikaciju HPI ose kod ove populacije. Ovi rezultati sugerišu da je populacija žutotrbog mukača sa ispitivanog lokaliteta lokalno adaptirana na specifične hidrološke uslove putem genetičke asimilacije.Environmental conditions in nature are constantly changing, requiring organisms to adjust in order to survive. The ability of a single genotype to alter its development, life-history traits, morphology, and behavior in response to environmental variation is known as phenotypic plasticity.
Habitat desiccation is one of the most severe abiotic stressors that disrupts the life cycle of amphibians. Many species of anurans can accelerate their development and complete metamorphosis before their aquatic habitats dry out. In this dissertation, we investigated how desiccation conditions affect life-history traits, morphology, and physiology in the yellow-bellied toad (Bombina variegata). Our results show that the studied population lacks the ability to accelerate development under desiccation stress. On the contrary, the larval period was either prolonged or unchanged, regardless of the developmental stage at which individuals were exposed to drying conditions. Desiccation negatively affected body length and mass, leading to a reduced growth rate and lower condition index at both the beginning (GS 42) and the end of metamorphosis (GS 46). However, these unfavorable conditions did not affect tail length or shape, nor did they impair the jumping performance of juvenile individuals. Additionally, no changes were observed in corticosterone levels or in parameters of the antioxidant system.
The absence of developmental acceleration, along with stable physiological responses under desiccation stress, suggests a possible modification of the HPI axis in this population. These findings indicate that the B. variegata population from the studied locality may be locally adapted to specific hydrological conditions through genetic assimilation