Search Results (69)

Human exposure to titanium dioxide nanoparticles (TiO₂ NPs) is common. These NPs are used in cosmetics, paint, food, and other products. Their nanometric size (<100 nm) allows entry into the bloodstream, from which they can reach organs and cells throughout the body. Although TiO₂ NPs have been reported to damage certain cell lines and organs and to alter cellular function, their impact on human menstrual blood mesenchymal stem cells (hMB-MSCs) is unknown. This study evaluated the effects of TiO₂ NPs on viability, proliferation, morphology, membrane-marker expression, and reactive oxygen species (ROS) production in primary cultures of hMB-MSCs derived from menstrual blood. Cells were exposed to different concentrations of TiO₂ NPs for 3, 7, and 14 days. TiO₂ NPs decreased hMB-MSC viability and proliferation in a concentration- and time-dependent manner. Cellular viability was reduced by up to 6%, 11%, and 18% at 3, 7, and 14 days, respectively (statistically significant vs. control). Cellular proliferation decreased by 3%, 5%, and 33% at 15.63, 62.5, and 250 μg/mL TiO₂, respectively. TiO₂ NPs were internalized and observed in the cytoplasm, forming perinuclear aggregates. NP-exposed cells showed reduced membrane expression of CD73 (7.9% decrease) and CD90 (25.72% decrease) compared with control cells. Finally, TiO₂ NPs at 15.63, 62.5, and 250 µg/mL reduced ROS generation by 56.79%, 62.79%, and 53.35%, respectively, after 4 h (statistically significant vs. control). In summary, exposure to high concentrations of TiO₂ NPs leads to intracellular nanoparticle deposits and alters key functions of human menstrual blood mesenchymal stem cells, including immunomodulation, immune protection, molecular behavior, cell differentiation, and regenerative capacity. Full article

The present study aimed to establish a physiologically based toxicokinetic (PBTK) model to investigate the absorption, retention, and transport of inhaled nano-sized titanium dioxide (TiO₂-NPs) particles in rats, thereby providing a basis for understanding the absorption, distribution, and elimination mechanisms of TiO₂-NPs in various organs. A detailed respiratory module and the Hill coefficient equation were adopted in the PBTK model. Calibration and validation of the model were conducted using the only two available inhalation biodistribution datasets for TiO₂-NPs found in the literature, encompassing different doses and exposure conditions. The overall fit with both datasets was acceptable with R² value of 0.95 in respiratory system and 0.88 in the secondary organs. The sensitivity analysis indicated that the alveolar–interstitial transfer rate (K_{alv_inter}) and tissue–blood distribution coefficients (P_lu, P_li, P_ki) significantly influenced the retention of TiO₂-NPs in pulmonary regions and distribution to secondary organs, with these parameters exhibiting time-dependent behavior. The PBTK model demonstrates a good predictive performance for TiO₂-NPs content in all rat organs, with simulated values consistently ranging within 0.5- to 2-fold of the measured data. In last, we developed a PBTK model that can well predict the in vivo distribution of inhaled TiO₂-NPs and provided a novel computational tool for cross-species extrapolation of human inhalation exposure and subsequent biodistribution. Full article

Optical coherence tomography (OCT) phantoms are essential tools for calibrating imaging systems, validating diagnostic algorithms, and bridging technological advancements with clinical applications. This review explores the development and application of materials used in OCT phantoms, emphasising their optical, mechanical, and biochemical fidelity to biological tissues. Gelatin-based phantoms (n = 1.35) offer controllable absorbance and scattering, with penetration depths (PDs) of 500–2000 µm and scattering coefficients (SCs) of 5–20 cm⁻¹ but are unstable at room temperature. Silicone phantoms (n = 1.41) are durable and stable, with SCs of 10–15 cm⁻¹, suitable for long-term studies. Polydimethylsiloxane (PDMS) phantoms (n = 1.41) provide manageable optical properties and are used in microfluidic applications. Polyvinyl alcohol (PVA) phantoms (n = 1.48) mimic soft tissue mechanics, with SCs of 5–15 cm⁻¹, but require freeze–thaw cycles. Fibrin phantoms (n = 1.38) simulate blood clotting, with SCs of 5–20 cm⁻¹. Scattering particles like polystyrene (n = 1.57) and titanium dioxide (TiO₂, n = 2.49) offer modifiable properties, while silica microspheres (SiO₂, n = 3.6) and gold nanoshells (n = 2.59) provide customisable optical characteristics. These materials and particles are crucial for simulating biological tissues, enhancing OCT imaging, and developing diagnostic applications. Despite progress, challenges persist in achieving submicron resolution, long-term stability, and cost-effective scalability. Full article

This article compares the properties of the diamond-like carbon (DLC) coating with those of ZrN and (Zr,Hf)N coatings deposited on the Ti-6Al-4V titanium alloy substrate. To improve substrate adhesion during the deposition of the DLC coating, preliminary etching with chromium ions was conducted, ensuring the formation of a chromium-saturated diffusion surface layer in the substrate. A Si-DLC layer followed by a pure DLC layer was then deposited. The hardness of the coatings, their surface morphology, fracture strength in the scratch test, and tribological properties and wear resistance in the pin-on-disk test in contact with Al₂O₃ and steel indenters were investigated. The structure of the DLC coating was studied using transmission electron microscopy, and its corrosion resistance in an environment simulating blood plasma was also investigated. In the pin-on-disk test in contact with Al₂O₃ and AISI 52100 indenters, the DLC-coated sample demonstrates a much lower friction coefficient and significantly better wear resistance compared to the nitride-coated and uncoated samples. Both nitride coatings—(Zr,Hf)N and ZrN—and the DLC coating slow down the corrosive dissolution of the base compared to the uncoated sample. The corrosion currents of the (Zr,Hf)N-coated samples are 37.01 nA/cm², 20% higher than those of the ZrN-coated samples. The application of (Zr,Hf)N, ZrN, and DLC coatings on the Ti-6Al-4V alloy significantly inhibits dissolution currents (by 30–40%) and increases polarization resistance 1.5–2.0-fold compared to the uncoated alloy in 0.9% NaCl at 40 °C. Thus, the DLC coating of the described structure simultaneously provides effective wear and corrosion resistance in an environment simulating blood plasma. This coating can be considered in the manufacture of medical products (in particular, implants) from titanium alloys, including those functioning in the human body and subject to mechanical wear (e.g., knee joint endoprostheses). Full article

Nowadays, developing countries have seen a reduction in male reproductive parameters, and it has been linked to the exposure of endocrine disrupting chemicals (EDCs), which are able to mimic or disrupt steroid hormone actions. Also, nanoparticles have shown effects on the male reproductive system, in particular the use of TiO₂-NPs in drugs, cosmetics, and food as pigment additives, and, thanks to their small size (1–100 nm), provide themselves the opportunity to be internalized by the body and pass the blood–testis barrier (BTB). Therefore, TiO₂-NPs can act on spermatogenesis and spermatozoa. In this study, we carried out an in vitro assay on human spermatozoa to evaluate the effects of TiO₂-NPs at the concentrations of 500, 250, 100, and 50 ppm. Exposure did not statistically alter sperm parameters (e.g., motility and viability) but induced damage to sperm DNA and the expression of biomarkers by spermatozoa. This immunofluorescence investigation showed a positivity for biomarkers of stress (HSP70 and MTs) on the connecting piece of spermatozoa and also for sex hormone binding globulin (SHBG) biomarkers. The SHBG protein acts as a carrier of androgens and estrogens, regulating their bioavailability; therefore, its expression in the in vitro assay did not rule out the ability of TiO₂-NPs to act as endocrine disruptors. Full article

Atenolol is a medication belonging to the class of drugs known as beta-blockers, used to treat high blood pressure (hypertension) and irregular heartbeats (arrhythmia). Their presence in the environment has serious impacts on humans, animals, and the water ecosystem. In this context, the aim of this study was to develop a simple voltammetric method for the determination of atenolol (ATN) using carbon paste electrodes modified with the nanomaterials TiO₂ and rGO/TiO₂. The analytical performance of the modified sensor was evaluated using square wave voltammetry and cyclic voltammetry in 0.1 mol L⁻¹ acid sulfuric solution (H₂SO₄), pH 2. The nanocomposite electrode CPE/rGO/TiO₂ exhibited excellent electrocatalytic activity towards ATN oxidations at 0.1 mol L⁻¹ H₂SO₄ compared with unmodified carbon paste electrodes CPEs and those modified with titanium oxide, CPE/TiO₂. Different experimental and conditional parameters were optimized, such as supporting electrolytes, pH, amplitude, frequency, etc. Under optimal conditions, linear calibration curves were obtained, ranging from 1.7 to 23.2 µmol L⁻¹ for ATN with detection limits of 0.05 μmol L⁻¹. The modified nanocomposite CPE/rGO/TiO₂ sensor showed good sensitivity and good repeatability (RSD ≤ 0.61%) for ATN determination. The proposed sensor is mechanically robust and presented reproducible results and a long useful life. In order to verify the usefulness of the developed methods, the nanocomposite sensor CPE/rGO/TiO₂ was applied for the detection of atenolol in real samples (pharmaceutical tablets without any pre-treatment). The excipients present in the tablets did not interfere in the assay. Recoveries ranging from 97.7% to 106% were obtained. The results showed that the CPE/rGO/TiO₂ voltammetric sensor could be successfully applied in the routine quality control of ATN in complex matrices. Full article

Background: Accurate assessment of therapy response to chemotherapy could possibly offer a bladder-sparing approach in selected patients with localized muscle-invasive bladder cancer (MIBC). The aim of this study was to evaluate whether [¹⁵O]H₂O PET/MRI can be used for assessment of complete local pathological response to preoperative chemotherapy in patients with MIBC. Methods: This prospective pilot study included 13 patients with MIBC treated with neoadjuvant or induction chemotherapy and subsequent radical cystectomy. Patients underwent a [¹⁵O]H₂O PET/MRI scan before chemotherapy and another scan after chemotherapy before radical cystectomy. Volumes of interest were delineated on T2-weighted MRI and transferred to parametric images for dynamic analysis. Tumor blood flow (TBF) was estimated by [¹⁵O]H₂O PET. Changes in TBF were compared with histopathology. The Wilcoxon matched-pairs signed-ranks test was used for comparing pre- and post-chemotherapy measurements. Results: Mean TBF decreased by 49%. Mean TBF in complete responders (ypT0N0/ypTis) was not significantly different from non-complete responders (≥ypT1) (p = 0.52). Conclusions: Despite a measurable decrease in TBF after chemotherapy treatment, we were not able to estimate a TBF threshold for identifying complete responders to chemotherapy for MIBC patients. Further studies are needed to elucidate the potential of [¹⁵O]H₂O PET/MRI in assessing therapy response in MIBC. Full article

Among brain tumors, glioblastoma (GBM) is very challenging to treat as chemotherapeutic drugs can only penetrate the brain to a limited extent due to the blood–brain barrier (BBB). Nanoparticles can be an attractive solution for the treatment of GBM as they can transport drugs across the BBB into the tumor. In this study, normal and GBM organoids comprising six brain cell types were developed and applied to study the uptake, BBB penetration, distribution, and efficacy of fluorescent, ultrasmall gold nanoparticles (AuTio-Dox-AF647s) conjugated with doxorubicin (Dox) and AlexaFluor-647-cadaverine (AF647) by confocal laser scanning microscopy (CLSM), using a mixture of dissolved doxorubicin and fluorescent AF647 molecules as a control. It was shown that the nanoparticles could easily penetrate the BBB and were found in normal and GBM organoids, while the dissolved Dox and AF647 molecules alone were unable to penetrate the BBB. Flow cytometry showed a reduction in glioblastoma cells after treatment with AuTio-Dox nanoparticles, as well as a higher uptake of these nanoparticles by GBM cells in the GBM model compared to astrocytes in the normal cell organoids. In summary, our results show that ultrasmall gold nanoparticles can serve as suitable carriers for the delivery of drugs into organoids to study BBB function. Full article

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 μg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests’ results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests’ results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m² (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study. Full article

The escalating utilization of titanium dioxide nanoparticles (TiO₂ NPs) in everyday products has sparked concerns regarding their potential hazards to pregnant females and their offspring. To address these concerns and shed light on their undetermined adverse effects and mechanisms, we established a pregnant rat model to investigate the impacts of TiO₂ NPs on both maternal and offspring health and to explore the underlying mechanisms of those impacts. Pregnant rats were orally administered TiO₂ NPs at a dose of 5 mg/kg body weight per day from GD5 to GD18 during pregnancy. Maternal body weight, organ weight, and birth outcomes were monitored and recorded. Maternal pathological changes were examined by HE staining and TEM observation. Maternal blood pressure was assessed using a non-invasive blood analyzer, and the urinary protein level was determined using spot urine samples. Our findings revealed that TiO₂ NPs triggered various pathological alterations in maternal liver, kidney, and spleen, and induced maternal preeclampsia-like syndrome, as well as leading to growth restriction in the offspring. Further examination unveiled that TiO₂ NPs hindered trophoblastic cell invasion into the endometrium via the promotion of autophagy. Consistent hypertension and proteinuria resulted from the destroyed the kidney GBM. In total, an exposure to TiO₂ NPs during pregnancy might increase the risk of human preeclampsia through increased maternal arterial pressure and urinary albumin levels, as well as causing fetal growth restriction in the offspring. Full article

Microneedles are of great interest in diverse fields, including cosmetics, drug delivery systems, chromatography, and biological sensing for disease diagnosis. Self-dissolving ultrafine microneedles of pure sodium hyaluronate hydrogels were fabricated using a UV-curing TiO₂-SiO₂ gas-permeable mold polymerized by sol-gel hydrolysis reactions in nanoimprint lithography processes under refrigeration at 5 °C, where thermal decomposition of microneedle components can be avoided. The moldability, strength, and dissolution behavior of sodium hyaluronate hydrogels with different molecular weights were compared to evaluate the suitability of ultrafine microneedles with a bottom diameter of 40 μm and a height of 80 μm. The appropriate molecular weight range and formulation of pure sodium hyaluronate hydrogels were found to control the dissolution behavior of self-dissolving ultrafine microneedles while maintaining the moldability and strength of the microneedles. This fabrication technology of ultrafine microneedles expands their possibilities as a next-generation technique for bioactive gels for controlling the blood levels of drugs and avoiding pain during administration. Full article

The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO₂) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work. Full article

Titanium oxide nanoparticles can penetrate the blood–brain barrier, infiltrate the central nervous system, and induce neurotoxicity. One of the most often utilized nanoparticles has been investigated for their neurotoxicity in many studies. Nonetheless, there remains an unexplored aspect regarding the comparative analysis of particles varying in size and nanoparticles of identical dimensions, both with and devoid of surface coating. In the current study, we synthesized two differently sized nanoparticles, TiO₂-10 (10 nm) and TiO₂-22 (22 nm), and nanoparticles of the same size but with a polyvinylpyrrolidone surface coating (TiO₂-PVP, 22 nm) and studied their toxic effects on neural PC-12 cells. The results highlighted significant dose- and time-dependent cytotoxicity at concentrations ≥10 μg/mL. The exposure of TiO₂ nanoparticles significantly elevated reactive oxygen and nitrogen species levels, IL-6 and TNF-α levels, altered the mitochondrial membrane potential, and enhanced apoptosis-related caspase-3 activity, irrespective of size and surface coating. The interaction of the nanoparticles with acetylcholinesterase enzyme activity was also investigated, and the results revealed a dose-dependent suppression of enzymatic activity. However, the gene expression studies indicated no effect on the expression of all six genes associated with the dopaminergic system upon exposure to 10 μg/mL for any nanoparticle. The results demonstrated no significant difference between the outcomes of TiO₂-10 and TiO₂-22 NPs. However, the polyvinylpyrrolidone surface coating was able to attenuate the neurotoxic effects. These findings suggest that as the TiO₂ nanoparticles get smaller (towards 0 nm), they might promote apoptosis and inflammatory reactions in neural cells via oxidative stress, irrespective of their size. Full article

Nanomaterials such as titanium dioxide and magnetite are increasingly used in several fields, such as water remediation and agriculture. However, this has raised environmental concerns due to potential exposure to organisms like humans. Nanomaterials can cause adverse interactions depending on physicochemical characteristics, like size, morphology, and composition, when interacting with living beings. To ensure safe use and prevent the risk of exposure to nanomaterials, their biocompatibility must be assessed. In vitro cell cultures are beneficial for assessing nanomaterial–cell interactions due to their easy handling. The present study evaluated the biocompatibility of TiO₂, Fe₃O₄, and TiO₂/Fe₃O₄ nanomaterials thermally treated at 350 °C and 450 °C in erythrocytes and HepG2 cells. According to the hemolysis experiments, non-thermally treated NMs are toxic (>5% hemolysis), but their thermally treated counterparts do not present toxicity (<2%). This behavior indicates that the toxicity derives from some precursor (solvent or surfactant) used in the synthesis of the nanomaterials. All the thermally treated nanomaterials did not show hemolytic activity under different conditions, such as low-light exposure or the absence of blood plasma proteins. In contrast, non-thermally treated nanomaterials showed a high hemolytic behavior, which was reduced after the purification (washing and thermal treatment) of nanomaterials, indicating the presence of surfactant residue used during synthesis. An MTS cell viability assay shows that calcined nanomaterials do not reduce cell viability (>11%) during 24 h of exposure. On the other hand, a lactate dehydrogenase leakage assay resulted in a higher variability, indicating that several nanomaterials did not cause an increase in cell death as compared to the control. However, a holotomographic microscopy analysis reveals a high accumulation of nanomaterials in the cell structure at a low concentration (10 µg mL⁻¹), altering cell morphology, which could lead to cell membrane damage and cell viability reduction. Full article

Chronic diseases of the urogenital tract, such as bladder cancer, prostate cancer, reproductive disorders, and nephropathies, can develop under the effects of chemical hazards in the working environment. In this respect, nanosized particles generated as by-products in many industrial processes seem to be particularly dangerous to organs such as the testes and the kidneys. Nephrotoxicity of element oxide particles has been studied in animal experiments with repeated intraperitoneal injections of Al₂O₃, TiO₂, SiO₂, PbO, CdO, CuO, and SeO nanoparticles (NPs) in total doses ranging from 4.5 to 45 mg/kg body weight of rats. NPs were synthesized by laser ablation. After cessation of exposure, we measured kidney weight and analyzed selected biochemical parameters in blood and urine, characterizing the state of the excretory system. We also examined histological sections of kidneys and estimated proportions of different cells in imprint smears of this organ. All element oxide NPs under investigation demonstrated a nephrotoxic effect following subchronic exposure. Following the exposure to SeO and SiO₂ NPs, we observed a decrease in serum creatinine and urea, respectively. Exposure to Al₂O₃ NPs caused an increase in urinary creatinine and urea, while changes in total protein were controversial, as it increased under the effect of Al₂O₃ NPs and was reduced after exposure to CuO NPs. Histomorphological changes in kidneys are associated with desquamation of the epithelium (following the exposure to all NPs except those of Al₂O₃ and SiO₂) and loss of the brush border (following the exposure to all NPs, except those of Al₂O₃, TiO₂, and SiO₂). The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. Compared to the controls, we observed statistically significant alterations in 42.1% (8 of 19) of parameters following the exposure to PbO, CuO, and SeO NPs in 21.1% (4 of 19)—following that, to CdO and Al₂O₃ NPs—and in 15.8% (3 of 19) and 10.5% (2 of 19) of indicators, following the exposure to TiO₂ and SiO₂ nanoparticles, respectively. Histomorphological changes in kidneys are associated with desquamation of epithelium and loss of the brush border. The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. The severity of cyto- and histological structural changes in kidneys depends on the chemical nature of NPs. These alterations are not always consistent with biochemical ones, thus impeding early clinical diagnosis of renal damage. Unambiguous ranking of the NPs examined by the degree of their nephrotoxicity is difficult. Additional studies are necessary to establish key indicators of the nephrotoxic effect, which can facilitate early diagnosis of occupational and nonoccupational nephropathies. Full article