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Studies of the Synthesis of Fused Isoxazoline/Isoquinolinones and Evaluation of the Antifungal Activity of Isoxazole-like Benzamide and Isoquinolinone Hybrids
No full textIsoxazole derivatives (isoxazoles, isoxazolines, and isoxazolidines) are present in
the structure of several natural products and/or pharmaceutically interesting compounds.
In this work, a synthetic study for the preparation of fused isoxazoline/isoquinolinone
hybrids is presented. The initial approach involving the sequential 1,3-dipolar cycloaddition
of nitrile oxides to indenone (to obtain the isoxazoline ring) and a Beckmann rearrangement
(to construct the isoquinolinone lactam system) was complicated by the formation of
fragmentation products during the latter. Therefore, the desired hybrids were successfully
reached by applying DDQ-mediated oxidation of the respective isoxazolidines. Based
on the results, key observations were made regarding the mechanism of the Beckmann
reaction. Moreover, selected isoxazole benzamides and fused isoxazoline/isoxazolidine
isoquinolinones were in vitro evaluated against a series of fungi strains (including a 2D
checkerboard assay with ketoconazole), revealing that some of these compounds exhibit
promising antifungal activity
Milestone for the ENLIGHT project: Dataset on larval development and behavior
No full textThis data set is a milestone of the WP1 work package of the Development under artificial light at night. Biological impact of light pollution on amphibians (ENLIGHT) project number #11120 financed by the Science Fund of the Republic of Serbia. Data set contains biometric parameters (body mass, growth rate) developmental rate and behavior (locomotor activity) of crested newts larvae exposed to different artificial light at night
From assesing chemical diversity to metabolic engineering: a case study on the genus Nepeta L.
No full textGenus Nepeta L. (subfam. Nepetoidae, fam. Lamiaceae) is known for the ability of the
majority of its representatives to produce iridoids with unique stereochemistry, which
display various bioactivities beneficial to human and animal health and can serve as
potent biopesticides. The bioactive properties of Nepeta species are typically attributed
to iridoid aglycones (IAs) such as nepetalactones (NLs), while the activities of their
glycosylated iridoids (IGs) remain largely unexplored. We here demonstrate how to tap
into the natural chemical diversity of iridoids (IAs and IGs) within the genus Nepeta,
analyze it across various levels of complexity, and apply this valuable knowledge as a
guide for metabolic engineering of plants. Based on the metabolomics and
transcriptomics data for phylodiverse/chemodiverse Nepeta taxa, as well as on the
reconstructed phylogenetic relations (DNA barcoding), it was possible to unambiguously
distinguish between taxa producing both NLs and IGs (chemotype A), taxa producing
only IGs (B), and taxa lacking iridoids (C). Molecular background of such a diversity was
interpreted in a phylogenetic context, which provided novel insights into the chemical
evolution within the genus Nepeta and, at the same time, pointed to the chemotypespecific intervention points for in planta metabolic engineering aimed at upscaling the
production of valuable Nepeta iridoids. Transient expression of key biosynthetic genes
in leaves of Nepeta sp. resulted in up-scaled production of stereo-variable NLs in
chemotype A taxa, but also in reestablishing their biosynthesis in chemotype B taxa.
This study opened up numerous possibilities to manipulate iridoid metabolism in
homologous and heterologous host organisms.Abstract, Proceedings: 4th Conference of Recent Trends in Science, Technology and Innovation; 2025 Mar 19-21; Pokhara, Nepal. Nepal: Pokhara University; 2025. p. 177
Associating Patient Responses with Drug Sensitivity in Non-Small Cell Lung Carcinoma Using an Immunoassay on Patient-Derived Cell Cultures
No full textAbstract
Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. Methods: We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients’ responses to therapy. We used Kaplan–Meier analysis to assess progression-free survival (PFS) differences among patient groups. Results: NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). Conclusions: A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients’ cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers
Gut microbiota composition of obesity resistant mice protects from high fat diet-induced steatosis
No full textBackground and aims: Obesity, which is characterized by excessive
fat accumulation, is a global health and economic burden. While most
people on a high-calorie diet develop obesity and related metabolic
diseases, some remain obesity resistant (OR). Obesity-induced
changes in the gut microbiota increase capacity of the microbiota to
harvest energy from the food, leading to fat accumulation and
metabolic complications. Therefore, the aim of this study was to
investigate the gut microbiota composition that contribute to obesity
resistance and protect against the development of hepatic steatosis
under a high-fat diet (HFD) regime.
Method: Male C57BL/6J mice were divided into two groups: a control
group fed a standard diet containing 10 kcal% fat (D12450J, Research
Diets) and a group fed a HFD containing 60 kcal% fat (D12492,
Research Diets,). After 14 weeks, the mice on HFD were classified as
obese or OR based on a 30% difference in body weight gain compared to the control group. The gut microbiota was analyzed by 16S rRNA
sequencing of bacterial DNA isolated from fecal samples. Liver and
small intestine sections were examined histologically, while changes
in fatty acid uptake in these tissues were assessed by Western blot.
Results: Functional prediction of the gut microbiota activity revealed
altered fatty acids metabolism and their biosynthesis in OR mice as
compared to the obese group. In addition, a negative correlation
between serum triglyceride levels and the relative abundance of
Lactobacillus was found, and a positive correlation with the relative
abundance of Desulfovibrio and Helicobacter. This change in the gut
microbiota composition paralleled the decreased protein levels of
free fatty acid transporters in the small intestine and liver of OR mice,
which likely protect the liver from ectopic lipid deposition and
steatosis characteristic for obese animals.
Conclusion: Increased abundance of Lactobacillus and decreased
abundance of Desulfovibrio and Helicobacter is microbiota profile
characteristic for obesity resistant animals, which is linked with
reduced fatty acid transporters and decreased accumulation of lipids
as compared to the obese animals. These results provide possible
candidates for the probiotics that could potentially protect against
obesity related complications.Abstract book of EASL Congress 2025; 2025 May 7-10; Amsterdam, the Netherlands. Amsterdam: Elsevier; 2025. p. S284. (Journal of Hepatology; Vol. 82. Suppl. 1)
Therapeutic Potential of Gentianaceae Family Plants in the Treatment of Diabetes and Its Complications
No full textDiabetes, a metabolic disorder characterized by hyperglycemia resulting from insulin insufficiency or impaired insulin sensitivity, is one of the major global health challenges. Persistent hyperglycemia in diabetes affects microcirculation, eyes, kidneys, liver, pancreas, muscle, and adipose tissue, which consequently leads to irreversible health issues such as retinopathy, nephropathy, neuropathy, cardiovascular complications, abnormalities of lipoprotein metabolism, and gastrointestinal dysfunction. Although available therapies are effective to some extent, they remain limited in efficacy and are often associated with side effects, underscoring the urgent need for novel treatment options. Traditionally, plant extracts and natural compounds have been used for centuries to treat diabetes and its complications. Plant extracts from the Gentianaceae family have emerged as a particularly promising source of bioactive compounds proven to be useful for the treatment of various diseases, including diabetes. This review provides a comprehensive overview of the most studied plant extracts and isolated compounds from the Gentianaceae family, with a focus on their use in diabetes treatment as well as their action in managing hyperglycemia, antioxidant activity, protection of pancreatic beta cells and associated complications. Numerous in vitro and in vivo studies have demonstrated their great potential to regulate blood glucose levels, reduce oxidative stress, alleviate tissue and organ damage—primarily in the liver and kidney—and improve lipid metabolism. To fully achieve this potential, future research should prioritize well-designed clinical trials to verify safety and efficacy in humans, conduct detailed molecular and cellular studies, standardize extraction and characterization methods to ensure reproducibility, and incorporate conservation biology principles into pharmacognostic investigations
Alfaxalone Modulates Autophagy in an In Vitro Model of Alzheimer’s disease
No full textDespite recent advancements in disease-modifying treatments for Alzheimer’s disease (AD), an effective therapy has yet to be identified. Neurosteroids and their analogs, potent positive allosteric modulators of GABA-A receptors, have recently been demonstrated to promote autophagy, a cellular degradation process severely disrupted in AD. Autophagy-modifying potential of synthetic neuroactive steroid Alfaxalone (ALX) was evaluated in vitro, using SH-SY5Y cells transfected either with empty PCDNA vector (control) or the human amyloid precursor protein (APP) harboring Swedish mutation (APP695Swe). Dose-dependent cytotoxicity of ALX was also examined. MTT and crystal violet assays showed a significant reduction in the viability of APPSwe expressing SH-SY5Y cells, with no further alteration following 24-hour ALX treatment across a 1–40 μM dose range. In addition, ALX pretreatment (30 minutes and 2 hours) had no toxic effect on SH-SY5Y cells. Immunoblot analysis further revealed that SH-SY5Y cells expressing APPSwe have increased LC3II and p62 levels, indicating enhanced autophagosome formation and impaired autophagic degradation. ALX treatment reverted the LC3II level in SHSY 5Y/APPSwe cells to the levels present in the controls. However, p62 levels remained unchanged, suggesting a persistent block in autophagic flux. ULK1 levels were unaffected under all conditions, implicating a ULK1-independent mechanism. Furthermore, ALX reduced amyloid beta (Aβ) accumulation in cells expressing mutant APP. Our findings support a neuroprotective role of ALX in AD and provide new evidence for its ability to modulate key molecular pathways involved in autophagy and amyloid processing in neuron-like cells. This multitarget action highlights the ALX as a promising candidate for further AD therapeutic development.Dragić M, editor. Book of abstracts: 9th Congress of Serbian Neuroscience Society; 2025 Oct 6-8; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2025
Preferred body temperature of the Caspian whipsnake (Dolichophis caspius, Gmelin, 1789) under laboratory conditions
No full textIn ectothermic animals, such as snakes, the body temperature depends on the temperature of the external environment. However, maintaining optimal body temperatures is crucial for various physiological functions such as feeding, locomotion, reproduction and immune response. In addition to interspecific variability, snake body temperatures can also vary at the intraspecific level (between populations, sexes and age classes) and are influenced by factors such as body size, presence of food in the stomach, gravidity, shedding phase and season. Although thermal biology is important for understanding organismal biology and conservation, it remains understudied in many common species. This study aimed to analyse the thermobiological traits of the Caspian whipsnake (Dolichophis caspius Gmelin 1789) under laboratory conditions, considering the effects of sex, age and season. We measured the cloacal temperatures of 15 adults (8 males and 7 females) and 14 juveniles (7 males and 7 females) hourly, from 09 to 18h. The snakes were exposed to a thermal gradient (17-45°C) in terraria. The influence of sex and age on the preferred body temperature (Tp) of individuals in the thermal gradient was modelled using general linear mixed models. We found that Tb did not differ between age groups (p=0.118) and sexes (p=0.238), but there was a statistically significant interaction (p=0.037). The mean value of the preferred body temperatures for all individuals was 24.5±4.9 °C (range 13.3-39.6°C). Set-point range (Tset) that represents the central 50% of all body temperatures selected in the thermal gradient, varied between 15.8°C and 31.9°C, with a mean of 24.3±3.5°C. The difference in Tb between seasons was only tested in juveniles and the results showed statistically significant effects of sex (p<0.001), season (p<0.001) and their interactions (p<0.001), with lower Tb in spring than in summer, and males having higher Tb than females in spring and lower in summer.Abstract booklet: Oral & Poster presentations: 23rd European Congress of Herpetology: SEH2025; 2025 Sep 8-12; Bonn, Germany. Societas Europaea Herpetologica; 2025. p. 282
Development of droplet digital PCR assays for environmental DNA detection of critically endangered sturgeon species
No full textAquatic organisms release DNA traces into the environment, enabling the molecular identification of
specific species or entire communities from a single water sample. In recent years, environmental DNA
(eDNA) methods have significantly enhanced freshwater biodiversity assessments and complemented
traditional monitoring approaches. Environmental DNA target screening using species-specific primers
and diagnostic endpoint droplet digital PCR (ddPCR) has proven to be highly specific and sensitive,
demonstrating its value in aquatic biomonitoring for detecting rare and endangered species that are
difficult to monitor with conventional methods. In this study, we developed the first ddPCR assays
targeting two native and critically endangered Danube sturgeon species — Stellate sturgeon (Acipenser
stellatus) and Russian sturgeon (Acipenser gueldenstaedtii). Currently, five out of six native Danube
sturgeons species are listed as critically endangered on the IUCN Red list, with their natural habitat
severely impacted by the construction of dams, pollution and overfishing. However, a defined
conservation and management plan for these species still does not exist. The main reason for this is the
lack of appropriate methodology to accurately assess the status of its remaining populations in the
Danube, which is essential for the implementation of legal and protective measures. The established
ddPCR assays provide a ready-to-use tool for the targeted and sensitive detection of presence, as well as
the estimation of population abundance of Acipenser stellatus and Acipenser gueldenstaedtii in the
Danube river, supporting ongoing and future regular monitoring and conservation efforts.The 4th Congress of Geneticists in Bosnia and Herzegovina with International Participation; 2025 Oct 2-4; Banja Luka, Bosnia and Herzegovina. Sarajevo: Institute for Genetic Engineering and Biotechnology, University of Sarajevo ; 2025. (Genetics & Applications; Special ed.)