Purpose: Nanoparticles are resources of advanced nanotechnology being present in several products. Titanium dioxide nanoparticles are among the five most widely used NP currently expanding their benefits from the oil industry to the areas of diagnostic medicine due to their properties and small size. However, its impact on human health is still controversial in the literature. We aimed to evaluate the cytotoxicity of a new titanium NP functionalized with sodium carboxylic ligand (COOH⁻Na⁺) in human keratinocytes (HaCaT) and human fibroblasts (HDFn). Methods: The physical-chemical characterization was performed by the transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential techniques, respectively. MTT and LDH assays were used to assess cytotoxicity and cell membrane damage respectively, ELISA to identify the inflammatory profile and, reactive oxygen species assay and cytometry to detect reactive oxygen species and their relationship with apoptosis/necrosis mechanisms. Results: The results demonstrated a decrease in cell viability at the highest concentrations tested for both cell lines, but no change in LDH release was detected for the HaCaT. The cell membrane damage was found only at 100.0 μg/mL for the HDFn. It was demonstrated that cytotoxicity in the highest concentrations evaluated for both cell lines for the 72 h period. The HDFn showed damage to the cell membrane at a concentration of 100 μg/mL followed by a significant increase in reactive oxygen species production. No inflammatory profile was detected. The HaCaT showed apoptosis when exposed to the highest concentration evaluated and HDFn showed both apoptosis and necrosis for the same concentration. Conclusion: Thus, it is possible to conclude that the cytotoxicity mechanism differs according to the cell type evaluated, with HDFn being the most sensitive line in this case, and this mechanism can be defined in a dose and time dependent manner, since the highest concentrations also triggered death cell.

BACKGROUND/AIMS: The development of new nanomaterials has been growing in recent decades to bring benefits in several areas, especially carbon-based nanoparticles, which have unique physical-chemical properties and allow to take on several applications. Consequently, the use of new nanomaterials without previous toxicological studies raises concern about possible harmful health effects. The aim of this study was to investigate the cytotoxic profile of a new multi-walled carbon nanotube (MWCNT) functionalized with tetraethylenepentamine called OCNT-TEPA using in vitro assays in murine macrophage cells linage J774 A.1. METHODS: OCNT-TEPA was characterized by transmission electron microscopy (TEM) and high resolution TEM (HR-TEM), scanning electron microscopy (SEM), zeta potential and dynamic light scattering (DLS), and its cytotoxic effects were evaluated at 24 and 48 hours by cell viability assays (MTT and NR), morphology and cell recovery (optic microscopy and clonogenic assay), formation of reactive oxygen (ROS) and nitric oxide (NO) species, inflammatory profile (IL-6 and TNF cytokines), mitochondrial membrane potential analysis (MMP), activation of the caspase 3 pathway and cell death (flow cytometry). RESULTS: The data showed a significant decrease in cell viability, increased production of ROS and NO, alteration of mitochondrial membrane potential, increased levels of inflammatory cytokines, alteration of cell morphology, activation of the Caspase 3 pathway and consequently cell death, in the highest concentrations of OCNT-TEPA tested in the periods of 24 and 48 hours. CONCLUSION: The analyses showed that OCNT-TEPA has a dose-dependent cytotoxic profile, which may be harmful to murine macrophages (J774 A.1) and may represent a health risk.

Depression and anxiety are mental health disorders that significantly impact global public health, affecting more than 280 million people with depression and 301 million with anxiety worldwide. These conditions impair individuals’ ability to engage in economic and personal activities and can lead to severe outcomes, such as suicide. Current research suggests that inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF), play crucial roles in the pathophysiology of these disorders, influencing neurotransmitters. Elevated cortisol levels, typically associated with anxiety, worsen these conditions through dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. Additionally, vitamin D deficiency has been linked to reduced production of dopamine and norepinephrine, hormones involved in depressive symptoms. This study utilized the Random Forest machine learning algorithm along with cross-validation to assess the importance of various biomarkers, including IL-1β, IL-6, IL-8, TNF, cortisol, vitamin D, NT-proBNP, CK-MB, troponin, myoglobin, and C-reactive protein (CRP), in volunteers of both sexes diagnosed with mental disorders. A single sample from each of the 96 participants was analyzed, consisting of 50 women and 46 men. The results revealed sex-specific differences in biomarker relevance, with vitamin D, CRP, and D-dimer being the most predictive for depression in men, while IL-6, CRP, and vitamin D were significant in women. For anxiety, vitamin D and myoglobin were important biomarkers in men, while IL-8 and vitamin D were key in women. The methodological strategy adopted, based on the use of Random Forest and cross-validation assessment, not only confirmed the robustness of the model but also reliably identified the most important biomarkers for the outcomes studied.

The influence of black carbon nanoparticles on J774.A1 murine cells was investigated with the objective of exploring the cytotoxicity of black carbon functionalized with ethylenediamine CB-EDA. The results showed that CB-EDA has a cytotoxic profile for J774.A1 macrophages in a time- and dose-dependent manner. When phagocytosed by the macrophage, CB-EDA triggers a mechanism that leads to apoptosis. In this process, there is an increase in oxidative stress pathways due to the activation of nitric oxide and then ROS. This causes an imbalance in redox function and a disruption of membrane integrity that occurs due to high levels of LDH, in addition to favoring the release of the pro-inflammatory cytokines IL-6, IL-12, and tumor necrosis factor (TNF) in an attempt to modulate the cell. However, these stimuli are not sufficient to repair the cell and the level of mitochondrial integrity is affected, causing a decrease in cell viability. This mechanism may be correlated with the activation of the caspasse-3 pathway, which, when compromised, cleaves and induces cells death via apoptosis, either through early or late apoptosis. In view of this, the potential for cell damage was investigated by analyzing the oxidative and inflammatory profile in the macrophage lineage J774.A1 and identifying potential mechanisms and metabolic pathways connected to these processes when cells were exposed to NP CB-EDA for both 24 h and 48 h.

Mental disorders, including anxiety, depression, and bipolar disorder, are frequently associated with metabolic, inflammatory, and behavioral alterations that modulate their clinical expression and increase the risk of physical comorbidities. This cross-sectional study aimed to characterize the profile of inflammatory, metabolic, and cardiac biomarkers in individuals with mental disorders compared to healthy controls, also considering anthropometric and lifestyle indicators. Fifty volunteers were evaluated and distributed into four groups: control, anxiety, depression, and bipolar disorder. All participants completed the Depression, Anxiety, and Stress Scale—21 items (DASS-21) and underwent blood collection for the assessment of inflammatory biomarkers such as C-Reactive Protein and its high-sensitivity detection (CRP/hs-CRP), Interleukins (IL-6, IL-1β) and Tumor Necrosis Factor alpha (TNF-α), metabolic biomarkers (vitamin D, cortisol, and D-dimer), and cardiac biomarkers such as N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), Creatine Kinase—MB (CK-MB), troponin I (cTnI), and myoglobin (Myo). The results showed a significantly higher body mass index (BMI) in clinical groups, particularly in groups with anxiety and depression. Biomarker analyses revealed significant differences in groups with mental disorders. Elevated levels of CRP (p = 0.0038), hs-CRP (p = 0.0048), and IL-6 (p = 0.0030) were identified in the anxiety group, while the depression group was characterized by reduced vitamin D levels (p = 0.0302). Individuals with bipolar disorder presented significantly higher levels of CK-MB (p = 0.0016), CRP (p < 0.0001), IL-6 (p = 0.0198), and IL-1β (p = 0.0067). It was also observed that most individuals with mental disorders did not engage in physical activity. This inactivity was associated with worse emotional scores, higher systemic inflammation, and vitamin D deficiency. These findings reinforce the existence of an integrated axis between metabolism, inflammation, and behavior, in which excess weight, sedentary lifestyle, and nutritional deficiencies synergistically contribute to the maintenance of psychiatric symptoms and metabolic vulnerability. Integrating biomarkers, BMI, and behavioral factors may aid in identifying clinical subphenotypes and guiding more precise and individualized therapeutic strategies.

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.