Melittin (Mel), the principal cytolytic peptide in honeybee venom (BV), has anticancer activity but limited selectivity. This study examined whether adsorption of Mel to Fe3O4 magnetic nanoparticles (MNPs and MNPs-Mel, respectively), alone or combined with magnetic hyperthermia (MH), modifies cytotoxicity and cell-death phenotype in A375 melanoma cells relative to HaCaT keratinocytes. BV, free Mel, and phospholipase A2 (PLA) were first screened by Alamar Blue assay to select dose-matched conditions; MNPs-Mel (50 or 100 µg/mL MNPs, equivalent to approximately 3 or 6 µg/mL Mel) was then compared with dose-matched free Mel and unfunctionalized MNPs, and the MNP-containing groups were additionally evaluated with MH. Outcomes included metabolic activity, Annexin V/propidium iodide flow cytometry, transmission electron microscopy (TEM), and clonogenic potential. At the lower dose, MNPs-Mel produced a larger Annexin-positive fraction in A375 than in HaCaT cells (28.30% vs. 11.80%) and a lower viable-cell fraction (71.64% vs. 87.55%); relative to dose-matched free Mel, the A375 response shifted toward early apoptosis. After MNPs-Mel plus MH, too few A375 cells remained for reliable cytometric acquisition, whereas HaCaT populations remained quantifiable and showed 25.56-29.45% apoptosis, predominantly late apoptosis. Free PLA produced smaller changes in metabolic activity than BV or Mel at composition-matched concentrations. TEM supported nanoparticle internalization and treatment-associated mitochondrial and lysosomal alterations. These findings suggest that MNP association changes the cellular presentation of low-dose Mel, while MH increases overall treatment intensity but may narrow the separation between malignant and nonmalignant cells.

Antibiotic resistance and biofilm-associated infections require sustainable antimicrobial platforms that combine efficacy with biocompatibility. Fermented matrices are attractive for green nanomaterial production because they provide reducing metabolites and surface-active capping compounds. Rooibos kombucha is a polyphenol-rich fermentation system with potential to serve as a biosynthetic matrix for silver nanoparticles (AgNPs). The present work aimed to develop a rooibos kombucha-enabled platform for the green biosynthesis of phytochemical-capped silver nanoparticles, AgNPs-K, and evaluate their antibacterial, antibiofilm, and in vivo activity. Rooibos kombucha was fermented for 14 days and profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS). AgNPs-K were generated using kombucha extract and AgNO3, purified, and characterized by ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and nanoparticle tracking analysis. Antibacterial activity against eight Gram-positive and Gram-negative reference pathogens was assessed by EUCAST-based microdilution and time-kill assays. Biofilm inhibition was measured by the crystal violet assay. In vivo toxicity and therapeutic efficacy were evaluated in Galleria mellonella larvae. AgNP formation was confirmed by a surface plasmon resonance (SPR) peak at 415 nm. TEM showed predominantly spherical nanoparticles with a main size range of 20-30 nm, a hydrodynamic diameter of 98 nm, and a zeta potential of -14.62 ± 0.04 mV. AgNPs-K showed overlapping minimum inhibitory concentration and minimum bactericidal concentration values of 1.14 µg/mL for Gram-positive species and 1.33 µg/mL for Gram-negative species. Time-kill assays showed rapid bactericidal activity after threshold concentrations were reached, with sustained suppression at 24 h. Biofilm formation was abolished at 40 µg/mL and strongly reduced at lower concentrations. AgNPs-K were non-toxic up to 400 µg/mL and improved survival in six of seven infection models. Fermented rooibos kombucha functions as an effective biosynthetic matrix for the green production of phytochemical-capped AgNPs. The resulting nanoparticles combine low-dose antibacterial and antibiofilm activity with favorable in vivo tolerability and efficacy, supporting fermentation-enabled nanobiotechnology strategies against biofilm-associated infection.

Gold has been used for centuries in both ornamental and medicinal contexts. More recently, gold compounds, containing ions or nanoparticles, have attracted attention for their anti-inflammatory, anticancer, and diagnostic applications. Therefore, concerns about systemic toxicity and biodistribution have prompted investigations into the biological effects of gold in animal models and humans. In the present study, we explored the impacts of a gold solution, used in chrysotherapy, on the reproductive function of male Wistar rats. Seven chronic intraperitoneal injections of sodium 3-aurothio-2-hydroxypropane-1-sulfonate at 30% of gold (allochrysine) were administered to adult male Wistar rats over a period of 2 weeks. The control rats received 0.9% NaCl solution. Our results showed that gold has no notable effect on the absolute weight of reproductive organs (testicles, epididymides, seminal vesicles, and the two caudae of the epididymides) and of nonreproductive organs (liver and brain) excepting the kidneys. The assessment of the fertility parameters showed a significant decline in the motility and viability of sperm cells. A slight reduction in the sperm density, and many malformations affecting the spermatozoa were detected, and the testosterone levels in rats' blood were also significantly diminished. Our study showed that administration of gold solution reduced sperm parameters and was a disruptive agent for the endocrine function of testicles. The oxidative stress generation, attributed to this heavy metal, led to a significant hypertrophy of the kidneys probably after inflammation. Thus, gold existing in different medical treatments could be classified as an endocrine disruptor and could be a detrimental factor of male fertility.

Invasive candidiasis caused by drug-resistant Candida species represents a critical global health challenge, with few novel therapeutic scaffolds under development. Here, silver nanoparticles were synthesized using a 21-day fermented Chun Mee kombucha tea extract (K-AgNPs) and characterized by UV-Vis spectroscopy, transmission electron microscopy, nanoparticle tracking analysis, and Fourier-transform infrared spectroscopy. LC-MS/MS profiling of the kombucha substrate documented a phytochemical landscape dominated by epigallocatechin (up to 122,631 µg/mL) and epigallocatechin gallate (up to 415 µg/mL), with a progressive ~80% decline in epicatechin and concomitant increases in gallic acid and chlorogenic acid across the 21-day fermentation. K-AgNPs obtained were spherical, 19.4 nm (±7.9 nm SD) in diameter, with a surface plasmon resonance peak at 415 nm. FTIR confirmed phenolic, carboxylate, and glycosidic surface capping. Antifungal susceptibility testing against eight Candida species, including the WHO critical-priority pathogen Candidozyma auris, showed concordant minimum inhibitory and minimum fungicidal concentrations of 0.80-1.60 µg/mL, confirming fungicidal activity. In vivo evaluation in Galleria mellonella larvae across six infection models demonstrated that K-AgNP treatment at the species-specific MIC significantly improved larval survival versus untreated infected controls (p < 0.01-0.001), while nanoparticle-only groups maintained ≥98% survival, indicating negligible toxicity. Co-treatment amplified total hemocyte mobilization, and K-AgNP-only larvae maintained hemocyte viability above 96% at all time points, indistinguishable from negative controls. Together, these findings demonstrate antifungal activity of K-AgNPs across the genus Candida in standardized in vitro and in vivo settings and provide justification for further investigation, including head-to-head comparison against licensed antifungals and physicochemical validation of nanoparticle stability under assay conditions.

Melittin-functionalized nanoparticles have emerged as a strategy to harness the potent anticancer activity of melittin while mitigating its narrow therapeutic window. Across diverse nanocarrier platforms, biological outcomes are highly dependent on the effective melittin concentration presented to tumour cells. This review systematically examines concentration-dependent anticancer effects of melittin-functionalized nanoparticles, focusing on quantitative dose-response metrics such as IC50 values, shifts in cytotoxic potency relative to free melittin, and concentration-linked safety margins. Along with some aspects concerning the molecular mechanisms of melittin, this review synthesizes evidence from preclinical studies to analyze how nanoparticle functionalization reshapes the concentration-effect relationship governing anticancer efficacy. This review concluded that there are three concentration regimes that govern the molecular outcome in tumours treated with melittin and melittin-functionalised nanomaterials. Collectively, the data demonstrate that nanoparticle association typically attenuates melittin's intrinsic lytic potency, requiring higher nominal concentrations to achieve cytotoxicity, while simultaneously enabling tumour-selective re-potentiation through targeting, activation, or intracellular release mechanisms. These concentration-dependent phenomena define the translational limits and opportunities of melittin-based nanomedicines.

Melittin (Mel) is a membrane-active peptide with potential anticancer activity, but its direct therapeutic application may be limited by nonspecific toxicity and delivery-related challenges. The study aimed to assess melittin-functionalized magnetic nanoparticles (MNPs-Mel) as a strategy to enhance antitumor activity in Caco-2 cells, with/without magnetic hyperthermia (MH) association. BJ fibroblasts were used as a normal human in vitro cellular model. The effects of free Mel (2.5 µg/mL), MNPs, and MNPs-Mel (50 µg/mL both) + MH (30 min at 355 kHz and 25 kA/m) were assessed using colorimetry (for viability), luminescence (ATP), and spectrophotometry (lactate) following different exposure conditions. The mechanism of apoptosis induction was evaluated by ELISA (caspase 8 and 9 levels). Transmission electron microscopy (TEM) was also used to evaluate nanoparticle morphology and treatment-associated cellular ultrastructural changes. Free Mel reduced viability in both cell lines, with Caco-2 cells showing greater sensitivity at lower concentrations. MNPs (with/without MH) produced limited and less consistent effects, whereas MNPs-Mel significantly reduced Caco-2 viability and ATP levels and increased LDH and caspase 9. MH further enhanced the effects of MNPs-Mel: reduced viability (57–58% of the control at 24 h and 72 h), decreased ATP levels (67% of the control at 24 h and 53% at 72 h), increased LDH levels (206% of the control at 24 h and 301% at 72 h), and induced the mitochondrial apoptotic pathway (caspase 9 increased with 2164% of the control at 72 h). TEM proved the internalization of both MNPs and MNPs-Mel and revealed extensive ultrastructural alterations concerning mitochondria and lysosomes produced by MNPs-Mel, particularly in the Caco-2 cells. These modifications were heavily increased by MNPs-Mel + MH exposure. Overall, these findings demonstrate that Mel functionalization increases the antitumor activity of Mel at lower doses and that MH further potentiates this effect in Caco-2 cells.

BACKGROUND:The growing use of gadolinium-based contrast agents (GBCAs) in medical imaging has raised concerns regarding the potential health risks associated with exposure to gadolinium (Gd), essentially its impact on reproductive function. The aim of this study was to investigate the effects of Gd exposure on the reproductive health of Wistar rats, focusing on alterations in reproductive organs ultrastructure especially epididymides and seminal vesicles. METHODS:The incidence of that rare earth, in the fertility parameters; namely motility, viability, density and eventual malformations of sperm as well as hormone measurement such as testosterone, was also studied. Adult male Wistar rats received soluble solution of Gd, their tissular structure was observed, with Transmission Electron Microscopy (TEM), their exocrine function was assessed and their testosterone levels were measured. RESULTS:Our results revealed significant changes in the epididymides and seminal vesicles ultrastructure and organelles, as well as decrease in testosterone levels. Furthermore, decreased fertility rates and raise in sperm malformations were observed in exposed rats. These results suggest that, at the administered doses, Gd seemed to reduce the fertility of rats, by alteration of tissue ultrastructure as well as exocrine and endocrine functions. Thus, exposure to Gd could negatively affect the reproductive system in rats, potentially offering insights into its effects on human reproductive health in the context of increasing clinical use of Gd. CONCLUSION:Further studies are warranted to elucidate the underlying mechanisms of Gd reproductive toxicity, like the exploration of oxidative status of reproductive organs after Gd exposition, and its long-term effects on fertility.

The behavior and incidence of the gadolinium (Gd) in the organism, has been carried out because of its increasing industrial and medical uses. Gadolinium was intraperitoneally administered to adult male Wistar rats, allowing access to organs via the blood. First, the nutritional status was daily determined using body weight and food intake of animals. Second, testicles, seminal vesicles, epididymides and their caudae, as well as liver, kidneys and brain weights were recorded. Third, treated and control organs were prepared for ultrastructural and microanalytical observations and were used for Gd quantification by ICP-MS technique. Seminal vesicles and the kidneys of treated rats showed significant increase in absolute weight. The ICP-MS showed that Gd was found in very important amounts in liver, testicle and urines collected over 24 h. The ultrastructural and microanalytical techniques showed that Gd was found in the lysosomes of Sertoli, Leydig and hepatic cells in the form of electron-dense grains associated with phosphorus. Ultrastructural alterations were also noticed in those cells. These original results showed that the lysosome was certainly exceeded since Gd was highly detected in many organs like liver and testicles. The presence of Gd in the rat organism seemed to cause toxicity and alteration in testicular cell organelles leading very probably to disruption in the reproductive tract functions. In this case, the organism seemed to activate elimination of Gd via hepatic biliary ducts and kidney excretion confirmed by the presence of Gd in the different analyzed liver territories and in the collected urines.

Phospholipase A2 (PLA2) is a prevalent molecule in the honeybee venom. Its importance is reflected by the number of scientists focused on studying it from various points of view. This review summarises a significant amount of data concerning this fascinating substance. Firstly, the origin and occurrence of PLA2, with similarities and differences among species or populations of bees are highlighted. Next, its synthesis, post-translational processing and structural features are described, followed by the PLA2 availability. In a larger section, the multiple effects of honeybee venom PLA2 are detailed, starting with the main ability as an enzyme to interact with biological membranes and to hydrolyse the sn-2 ester bond in 1,2-diacyl-sn-3-phosphoglycerides; the docking process, the substrate binding and the catalytic steps are analysed too. Then, the pro-/anti-inflammatory effect and allergenic property, the anticoagulant effect and the involvement of PLA2 in apoptosis are revised. Selected antiviral, antibiotic and antitumoral effects of PLA2, as well as its use in immunotherapy are mentioned as beneficial applications. Additionally, the mechanisms of toxicity of PLA2 are presented in detail. Finally, a number of anti-PLA2 compounds are enumerated. In each section, the features of the honeybee venom molecule are discussed in relation to PLA2s from other species.

Bee venom (BV) molecules, including melittin (Mlt), are known to modify the permeability of membranes. This paper assessed red blood cell (RBC) shape (by phase contrast microscopy) in relation to some of the parameters (haematology data) and calculated the RBC membranes’ water diffusional permeability (Pd) with 1H-NMR spectroscopy. Rats were injected for 30 days with either small daily doses of BV (VST) or Mlt (MST) or with high single doses of BV (VSLT) or Mlt (MSLT). The RBCs displayed aberrant shapes, all of the analysed parameters significantly changed, and the values of Pd were higher (and increased with temperature) in all of the treated groups compared to the control group. The RBCs in the venom-treated groups had the highest mean values (expressed in cm × s−1 × 103) of Pd at 37 °C—8.95 in the VSLT group and 8.69 in the VST group—which were followed by the MST and MSLT groups and the control group. Our results demonstrated the ability of Mlt to retain the ability to interact with the RBC membrane in vivo and proved that Mlt is the most important BV molecule involved in this process.

Research on metal nanoparticles is crucial for their application in diverse fields, requiring detailed assessments of their effects and potential. Galleria mellonella larvae have emerged as a valuable model for studying the impacts of metal nanoparticles, offering ethical and logistical advantages over traditional models. This systematic review synthesizes evidence on the application of Galleria mellonella in evaluating the toxicity, distribution, and therapeutic potential of metal nanoparticles. Adhering to PRISMA guidelines, a comprehensive database search (MEDLINE, Embase, Cochrane, Scopus, Google Scholar, Science Citation Index Expanded) was conducted using keywords related to Galleria mellonella and metal nanoparticles. The SYRCLE's risk of bias tool (adapted for G. mellonella) was used for risk of bias assessment. Out of 1696 initially identified studies, 31 met the inclusion criteria, encompassing research from 2011 to 2024. The included studies effectively demonstrate G. mellonella's capacity to model the toxicity of metal nanoparticles, their therapeutic potential in treating infections, and the impact on the innate immune response, bridging the gap between simpler in vitro assays and more complex mammalian models. Galleria mellonella stands out as a critical model for the early-stage development and evaluation of metal nanoparticles, particularly in assessing toxicity, therapeutic efficacy in infection treatment, and interaction with immune systems. This review underscores the larvae's role in metal nanoparticle research, advocating for its broader use to streamline development processes while minimizing ethical concerns.

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties.

COVID-19-associated rhino-orbital mucormycosis has become a new clinical entity. This study’s aim was to evaluate the histopathological and ultramicroscopic morphological aspects of this fungal infection. This was an observational retrospective study on eight patients from three tertiary centers in Romania. The tissue samples collected during functional endoscopic sinus surgery were studied through histopathological examination, scanning electron microscopy, and transmission electron microscopy. In the histopathological examination, the morphological aspects characteristic of mucormycosis in all cases were identified: wide aseptate hyphae with right-angle ramifications, which invade blood vessels. One case presented perineural invasion into the perineural lymphatics. And in another case, mucormycosis–aspergillosis fungal coinfection was identified. Through scanning electron microscopy, long hyphae on the surface of the mucosa surrounded by cells belonging to the local immune system were identified in all samples, and bacterial biofilms were identified in half of the samples. Through transmission electron microscopy, aseptate hyphae and bacterial elements were identified in the majority of the samples. Rhino-orbital-cerebral mucormycosis associated with COVID-19 produces nasal sinus dysbiosis, which favors the appearance of bacterial biofilms. The way in which the infection develops depends on the interaction of the fungi with cells of the immune system.

Hepatocellular carcinoma is the most common primary malignancy of the liver, with hepatocellular differentiation. It is ranked sixth among the most common cancers worldwide and is the third leading cause of cancer-related deaths. The most important etiological factors discussed here are viral infection (HBV, HCV), exposure to aflatoxin B1, metabolic syndrome, and obesity (as an independent factor). Directly or indirectly, they induce chromosomal aberrations, mutations, and epigenetic changes in specific genes involved in intracellular signaling pathways, responsible for synthesis of growth factors, cell proliferation, differentiation, survival, the metastasis process (including the epithelial–mesenchymal transition and the expression of adhesion molecules), and angiogenesis. All these disrupted molecular mechanisms contribute to hepatocarcinogenesis. Furthermore, equally important is the interaction between tumor cells and the components of the tumor microenvironment: inflammatory cells and macrophages—predominantly with a pro-tumoral role—hepatic stellate cells, tumor-associated fibroblasts, cancer stem cells, extracellular vesicles, and the extracellular matrix. In this paper, we reviewed the molecular biology of hepatocellular carcinoma and the intricate mechanisms involved in hepatocarcinogenesis, and we highlighted how certain signaling pathways can be pharmacologically influenced at various levels with specific molecules. Additionally, we mentioned several examples of recent clinical trials and briefly described the current treatment protocol according to the NCCN guidelines.

Purpose: Our study seeks to develop dual-modal organic-nanoagents for cancer therapy and real-time fluorescence imaging, followed by their pre-clinical evaluation on a murine model. Integrating NIR molecular imaging with nanotechnology, our aim is to improve outcomes for early-stage cutaneous melanoma by offering more effective and less invasive methods. This approach has the potential to enhance both photothermal therapy (PTT) and Sentinel Lymph Node Biopsy (SLNB) procedures for melanoma patients. Methods: NIR-797-isothiocyanate was encapsulated in poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) using a twostep protocol, followed by thorough characterization, including assessing loading efficiency, fluorescence stability, and photothermal conversion. Biocompatibility and cellular uptake were tested in vitro on melanoma cells, while PTT assay, with real-time thermal monitoring, was performed in vivo on tumor-bearing mice under irradiation with an 808 nm laser. Finally, ex vivo fluorescence microscopy, histopathological assay, and TEM imaging were performed. Results: Our PLGA NPs, with a diameter of 270 nm, negative charge, and 60% NIR-797 loading efficiency, demonstrated excellent stability and fluorescence properties, as well as efficient light-to-heat conversion. In vitro studies confirmed their biocompatibility and cellular internalization. In vivo experiments demonstrated their efficacy as photothermal agents, inducing mild hyperthermia with temperatures reaching up to 43.8 degrees C. Ex vivo microscopy of tumor tissue confirmed persistent NIR fluorescence and uniform distribution of the NPs. Histopathological and TEM assays revealed early apoptosis, immune cell response, ultrastructural damage, and intracellular material debris resulting from combined NP treatment and irradiation. Additionally, TEM analyses of irradiated zone margins showed attenuated cellular damage, highlighting the precision and effectiveness of our targeted treatment approach. Conclusion: Specifically tailored for dual-modal NIR functionality, our NPs offer a novel approach in cancer PTT and real-time fluorescence monitoring, signaling a promising avenue toward clinical translation.

Background: Peripheral nerve injuries (PNI) can generate important medium- and long-term disability, as patients mostly complain about associated pain, sensibility and, or motor deficit, and even psychological manifestations. Chitosan and different nanoparticles types were previously used in several studies as treatment of peripheral nerve injuries. The present study aimed to assess the hepatic responses at oral administration of simple chitosan solution and of magnetic iron oxide nanoparticles functionalized with chitosan (CMNPs) solution in an experimentally induced peripheral nerve injury. (2) Methods: Chitosan or CMNPs were oral administrated, for 21 days, to animals with peripheral nerve injury. The treated groups were compared with a control group (peripheric nerve injury without any treatment). The hepatic toxicity of administered solutions was analyzed histologically, through transmission electron microscopy (TEM) and through the oxidative stress parameters, in comparison with the control group. (3) Results: Liver tissue histological evaluation showed non-significant degeneration of hepatocytes in Chitosan group and, in CMNPs group, slight periportal inflammation. TEM investigation revealed nuclear and mitochondrial polymorphism and lipid accumulation in hepatocytes in Chitosan group, and in CMNPs group, irregular nucleus profiles and increased glycogen storage in cytosol. Oxidative stress analysis showed antioxidant hepatic effect of both treatments. (4) Conclusions: Compared to control group, both treatments produced significant increases of hepatic antioxidant protection, probably induced by chitosan properties. Histological modifications of the liver were minimal for both treatment groups. TEM investigation showed unspecific alterations of the hepatocytes structure. Keywords: chitosan; iron oxide magnetic nanoparticles; peripheral nerve injury; toxicity

Background/Objectives: The rapidly increasing rate of obesity has become an extremely important public health problem, particularly in developed countries. Obesity is associated with a range of health problems, often referred to as the metabolic syndrome. Adipose tissue is now regarded as an endocrine organ responsible for the hormonal secretion of adipokines, which are cytokines involved in various physiological processes. It has been established that adipokines play a key role in the regulation of many processes in the human body. The aim of the current study was to use an animal model to investigate the possible influence of obesity and adipokines on the gestational period, on the development of offspring, and to assess whether these changes are influenced by the administration of antioxidant agents and flavonoids. Methods: The present study was performed using 5 groups of 7 female Wistar albino rats. A control group was used to which a 5% lipid diet was administered, and the other 4 groups were fed an obesogenic 65% lipid diet. From the 4 groups that received obesogenic diet one group received no supplement, and the rest of 3 received Detralex, Sel-E-Vit and Rutin (antioxidants and flavonoids). Study times for both pregnant groups and offsprings: on day 15 of gestation, venous blood was drawn to determine adipokine (leptin and visfatin) levels; on days 18-22 ultrasound examination was performed to measure the thickness of adipose tissue in the abdominal wall; for each batch a number of 10 offspring were selected for the measurements (pup weight, brain weight, head length, head width, spine length, width between shoulder blades, coxal bone length), adipokine levels in the offspring (from brain tissue) were also determined, as well as the existence of changes in the brain tissue of the offspring identified by electron microscopy. Results: The results of the study showed that the high-fat diet (HFD) led to a significant increase in body weight and abdominal wall thickness in pregnant females compared to the control group. The levels of leptin and visfatin were also affected by the HFD, with leptin levels being significantly higher in the HFD group and visfatin levels being lower. In the offspring, the HFD group had a significantly higher body mass and brain weight compared to the control group. The anthropometric measurements of the offspring were also affected by the maternal diet, with the HFD group having larger dimensions overall. Interestingly, the offspring of the groups that received flavonoids in addition to the HFD had significantly smaller dimensions compared to both the HFD group and the control group. Conclusions: The results of this experimental study reinforce what is already known about the effects of obesity on the gestation period and offspring and at the same time, the current study highlights the existence of possible adverse effects of flavonoid compounds on the development of pregnancy and offspring, opening the way for future studies on the benefits and risks of using these compounds during gestational period.

Gold nanoparticles (Au-NPs) have been explored as potential vectors for enhancing the antitumor efficacy of doxorubicin (DOX) while minimizing its cardiotoxic effects. However, the impacts of DOX Au-NPs on cardiac function and oxidative stress remain inadequately understood. This study aimed to explore the effects of DOX Au-NPs in comparison to free DOX, focusing on oxidative stress markers, inflammation, ultrastructural changes, and cardiac function. Male rats were divided into the following four groups: control, citrate Au-NPs, DOX, and DOX Au-NPs. Cardiac function was assessed using echocardiography, and oxidative stress was evaluated through Nrf2, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, and the GSH/GSSG ratio. The ultrastructure of cardiac tissue was assessed by transmission electron microscopy (TEM). Rats treated with DOX Au-NPs exhibited significant cardiac dysfunction, as indicated by a reduction in fractional shortening and ejection fraction. Oxidative stress markers, including elevated MDA levels and a reduced GSH/GSSG ratio, were significantly worse in the DOX Au-NP group. SOD levels decreased, indicating compromised antioxidant defenses. Citrate Au-NPs also caused some alterations in cardiac function and ultrastructure but without other molecular alterations. DOX Au-NPs failed to mitigate cardiotoxicity, instead exacerbating oxidative stress and cardiac dysfunction. DOX Au-NPs possess cardiotoxic effects, necessitating further investigation into alternative nanoparticle formulations or therapeutic combinations to ensure both efficacy and safety in cancer treatment.