Comparative Toxicity Research Articles

Comparative cellular toxicity between silver and poly (lactic-co-glycolic acid) nanoparticles

Nanoparticles composed of poly (lactic‑co‑glycolic acid) (PLGANPs) and silver (AgNPs) are relevant in the context of their interactions with biological systems. This study aims to evaluate the potential in vitro cytotoxic effects of both PLGANPs and AgNPs on a human colorectal adenocarcinoma cell line (Caco‑2). The impact of nanoparticles on cellular toxicity, morphology, microvilli density and viscoelasticity were assessed. After 48 hours incubation with PLGANPs, cells exhibited a modest proliferation compared to the control (6 to14%), low reactive nitrogen species (RNS) production (2 μM) and higher microvilli densities. In contrast, AgNPs displayed significant toxicity (LC50 = 3.76 μg/mL) and elevated RNS production.

Assessing the Comparative Toxicity of Salvia Officinalis Extracts and Copper Sulphate on Melanopsis Nodosa, a Freshwater Snail

This study investigates the molluscicidal properties of Salvia officinalis extracts against Melanopsis nodosa snails, with a focus on environmentally friendly alternatives to traditional chemical molluscicides. Melanopsis nodosa, a common freshwater snail in Iraq, is an intermediate host for diseases affecting humans and animals. Traditional molluscicides, such as copper sulphate, pose environmental and non-target organism risks. S. officinalis, known for various medicinal uses, was explored for its potential molluscicidal activity. Snails were collected from Muhyii Canal, Baghdad, and exposed to different concentrations of S. officinalis extracts and copper sulphate in controlled laboratory conditions. The study evaluated mortality rates at 24-, 48-, 72-, and 96-hours exposure, using the WHO method for molluscicide testing and Probit analysis for mortality calculation. Results showed significant molluscicidal activity of S. officinalis extracts, with the LC50 values of 15.53 ppm (24 hrs), 6.821 ppm (48 hrs), 4.288 ppm (72 hrs), and 0.0735 ppm (96 hrs). Compared to copper sulphate, the extracts were less effective but still significant, indicating the potential of S. officinalis as an environmentally friendly molluscicide. This study contributes to the search for safer molluscicides, highlighting S. officinalis extracts' effectiveness against M. nodosa. These findings could aid in controlling snail populations, thereby reducing the spread of snail-borne diseases, with lower environmental impact compared to traditional chemical molluscicides. Further research is suggested to understand the exact mechanism of snail mortality caused by these extracts.

Chronic oral toxicity protocol for adult solitary bees (Osmia bicornis L.): Reduced survival under long-term exposure to a “bee-safe” insecticide

Pollinators are essential for crop productivity. Yet, in agricultural areas, they may be threatened by pesticide exposure. Current pesticide risk assessments predominantly focus on honey bees, with a lack of standardized protocols for solitary bees. This study addresses this gap by developing a long-term oral exposure protocol tailored for O. bicornis. We conducted initial trials to determine optimal container sizes and feeding methods, ensuring high survival rates and accurate syrup consumption measurements. A validation test involving five laboratories was then conducted with the insecticide Flupyradifurone (FPF). Control mortality thresholds were set at ≤ 15% at 10 days. Three laboratories achieved ≤10%, demonstrating the protocol's effectiveness in maintaining healthy test populations. The seasonal timing of experiments influenced control mortality, underscoring the importance of aligning tests with the natural flight period of the population used. Our findings revealed dose-dependent effects of FPF on syrup consumption, showing stimulatory effects at lower concentrations and inhibitory effects at higher ones. The 10-day median lethal daily dose (LDD50) of FPF for O. bicornis (531.92 ng/bee/day) was 3.4-fold lower than that reported for Apis mellifera (1830 ng/bee/day), indicating Osmia's higher susceptibility. Unlike other insecticides, FPF did not exhibit time-reinforced toxicity. This study introduces a robust protocol for chronic pesticide exposure in solitary bees, addressing a critical gap in current risk assessment. Based on its low risk to honey bees and bumblebees, FPF is approved for application during flowering. However, our results suggest that it may threaten Osmia populations under realistic field conditions. Our findings underscore the need for comparative toxicity studies to ensure comprehensive protection of all pollinators and the importance of accounting for long term exposure scenarios in risk assessment. By enhancing our understanding of chronic pesticide effects in solitary bees, our study should contribute to the development of more effective conservation strategies and sustainable agricultural practices.

Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients.

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B-cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high-dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow-up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression-free survival (PFS) (HR 1.80 CI 1.11-2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86-2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40-1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22-0.94, p = 0.032). Age 60-69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60-69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.

Comparative Toxicity Analysis of 3M ESPE Clinpro Tooth Crème and VOCO Profluorid Varnish in Artemia Nauplii and Zebrafish Larvae

Comparative Toxicity Analysis of 3M ESPE Clinpro Tooth Crème and VOCO Profluorid Varnish in Artemia Nauplii and Zebrafish Larvae

Real World Outcomes In Patients With Recurrent, Advanced Or Metastatic Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab

ObjectivePatients with endometrial cancer who progress following first line therapy have improved survival outcomes with pembrolizumab and lenvatinib (pem/len) compared with standard of care chemotherapy, as demonstrated in KEYNOTE-775. This was in a group of trial patients with a good performance status and excluded those with carcinosarcoma histology. In KEYNOTE-775 pem/len was associated with significant toxicity leading to dose reductions, treatment cessation and patient morbidity. We set out to assess the tolerability, toxicity and outcomes following pem/len for patients with recurrent, advanced or metastatic endometrial cancer in a real-world setting. MethodsUK centres treating patients with pem/len for advanced endometrial cancer within the compassionate access programme were approached. Retrospective data was analysed for those treated between May 2022 and June 2023. Data on patient demographics, treatment, toxicity and outcomes was extracted from medical records. Toxicity and tolerability were compared in those over and under the age of 70. Results7 centres returned data for 70 patients. Median age of patients was 68.5 years (range 45-85) with a performance status of 0-1 in 77.1% and of 2 in 22.9%. Histological subtypes included serous (34.3%), endometrioid (32.9%), carcinosarcoma (14.3%), clear cell (7.1%), mixed (2.9%) and other (8.6%). Grade ≥3 toxicity was reported in 55.7% with any-grade toxicity observed in 85.7%. In those aged ≥70 years (n=30) the rate of grade ≥3 toxicity was 60.0%. Rates of dose reduction of lenvatinib were 64.3% and toxicity-related treatment interruption 45.7%. The 6-month progression-free and overall survival rates were 54.0% (95%CI: 39.0-66.8) and 70.1% (95%CI:56.5-80.1) respectively. ConclusionThis real-world, observational study of pem/len showed comparable tolerability, toxicity and outcomes to previously reported clinical trial data. Our cohort included patients with a poorer PS and a broader range of histological subtypes including carcinosarcoma.

Optimization and Appraisal of Nintedanib-Loaded Mixed Polymeric Micelles as a Potential Nanovector for Non-Invasive Pulmonary Fibrosis Mitigation.

Nintedanib (NTD), a triple tyrosine kinase receptor inhibitor, is the recommended first-line tackling option for idiopathic pulmonary fibrosis (IPF). Nevertheless, the adequacy of NTD is curtailed by issues associated with its low solubility, first-pass effect, poor bioavailability, and liver toxicity. The objective of our work was to develop a non-invasive intratracheal (i.t.) nanoparadigm based on NTD-loaded polymeric mixed micelles (NTD-PMMs) that can effectively treat IPF by sustaining the release of NTD, and snowballing its bioavailability, solubility, and efficacy. Design-Expert® software was used to optimize various NTD-PMMs formulations via Box-Behnken design adopting the thin-film hydration technique. The optimum formulation was chosen and in vivo tested in a rat model to explore its comparative bioavailability and toxicity. The formulation composition with 309.217 mg of Soluplus, 150 mg of Tween 80, and 40 mg of sodium deoxycholate was found to fulfill the requisites of an optimum NTD-PMMs formulation. The optimum NTD-PMMs formulation divulged 90.26% entrapment efficiency with a surface charge of -14.72 mV and a nanoscale diameter of 61.36 nm. Also, it substantially sustained the release of NTD by 66.84% after 24 h and manifested a pronounced stability. In vivo histopathology investigations verified the safety of NTD-PMMs delivered intratracheally. Moreover, pharmacokinetic analyses disclosed accentuated relative bioavailability of the optimized NTD-PMMs by 2.4- and 3.82-fold as compared with both the i.t. and oral crude NTD suspensions, respectively. Overall, the current results elicited the potential of PMMs to serve as a promising pulmonary nanovector for the targeted delivery of NTD.

Comparative toxicity of insecticides to the haemocytes of honeybee, Apis mellifera (Hymenoptera: Apidae) under laboratory conditions

Comparative toxicity of insecticides to the haemocytes of honeybee, Apis mellifera (Hymenoptera: Apidae) under laboratory conditions

Structure-Dependent Distribution, Metabolism, and Toxicity Effects of Alkyl Organophosphate Esters in Lettuce (Lactuca sativa L.).

This study provides a comprehensive investigation into the structure-dependent uptake, distribution, biotransformation, and potential toxicity effects of alkyl organophosphate esters (OPEs) in hydroponic lettuce (Lactuca sativa L.). Trimethyl, triethyl, and tripropyl phosphates were readily absorbed and acropetally translocated, while tributyl, tripentyl, and trihexyl phosphates accumulated mainly in lateral roots. The acropetal translocation potential was negatively associated with log Kow values. Trimethyl and triethyl phosphates are less prone to biotransformation, while a total of 14 novel hydrolysis, hydroxylated, and conjugated metabolites were identified for other OPEs using nontarget analysis. The extent of hydroxylation decreases from tripropyl phosphate to trihexyl phosphate, but multiple hydroxylations occurred more frequently on longer chain OPEs. Further comparative toxicity test revealed that hydrolyzed and hydroxylated metabolites have stronger toxic effects on Ca2+-dependent protein kinases (CDPK) than their parent OPEs. Dibutyl 3-hydroxybutyl phosphate particularly induces upregulation of CDPK in lateral roots of lettuce, probably associated with adenine reduction that may play an important role in the self-defense and detoxification processes. This study contributes to understanding the uptake and transformation behaviors of alkyl OPEs as well as their associations with a toxic effect on lettuce. This emphasizes the necessary evaluation of the environmental risk of the use of OPEs, particularly focusing on their hydroxylated metabolites.

Comparison between Trans-Arterial Chemoembolization Followed by Stereotactic Body Radiation Therapy and Trans-Arterial Chemoembolization Alone in BCLC Stage B Hepatocellular Carcinoma: A Pilot Study.

Both Stereotactic Body Radiation Therapy (SBRT) and Trans-arterial Chemoembolization (TACE) are now being widely used to treat advanced hepatocellular carcinoma (HCC) and can improve tumor local control rates. We aimed at evaluating the efficacy and toxicity of combining SBRT and TACE in comparison to TACE alone in unresectable HCC. 42 unresectable Barcelona Clinic Liver Cancer (BCLC) stage B HCC Child Pugh (CP) A patients were randomized to receive either: TACE alone (Arm A) or TACE followed by SBRT (Arm B). Dose prescribed was 40Gy in 5consecutive daily fractions over 1 week . We compared the local control (LC), Progression free survival (PFS), overall survival (OS) and toxicity between the two arms. 22 patients were in arm A versus 20 patients in arm B with median follow up 20 months starting recruitment from April 2021 till January 2023. Both LC, PFS were significantly better in Arm B. Complete remission (CR) rate was 54.5% and 75% in Arm A and B, respectively. Median PFS was 16 months in Arm B compared to 11 months in Arm A (p =0.003). Median OS was not reached in both arms. Both arms had comparable toxicities. Adding SBRT to TACE in advanced HCC, is safe and feasible with better efficacy in terms of LC and PFS with comparable side effects, in comparison to TACE alone.

Comparative toxicity and enzymatic detoxification responses in Spodoptera frugiperda (Lepidoptera: Noctuidae) to two insecticides

The fall armyworm (FAW), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), poses a significant threat to food security, necessitating effective management strategies. While chemical control remains a primary approach, understanding the toxicity and detoxification mechanisms of different insecticides is crucial. In this study, we conducted leaf-dipping bioassays to assess the toxicity of quinalphos and beta-cypermethrin·emamectin benzoate (β-cyp·EMB) on S. frugiperda larvae. Additionally, we assessed the response of alterations in CarE, GST, MFO, and AChE activities to sublethal concentrations of these insecticides over various treatment durations. Results indicated that β-cyp·EMB exhibited higher toxicity than quinalphos in S. frugiperda. Interestingly, the highest activities of GST, CarE, MFO, and AChE were observed at 6 h exposure to LC10 and LC25 of β-cyp·EMB, surpassing equivalent sublethal concentrations of quinalphos. Subsequently, GST and CarE activities exposure to β-cyp·EMB steadily decreased, while MFO and AChE activities exposure to both insecticides was initially decreased then increased. Conversely, two sublethal concentrations of quinalphos notably enhanced GST activity across all exposure durations, with significantly higher than β-cyp·EMB at 12–48 h. Similarly, CarE activity was also increased at various durations. Our research has exhibited significant alterations in enzyme activities exposure to both concentration and duration. Furthermore, Pearson correlation analysis showed significant correlations among these enzyme activities at different treatment durations. These findings contribute to a better understanding of detoxification mechanisms across different insecticides, providing valuable insights for the rational management of S. frugiperda populations.

Toxic risk assessment of selected metals in infant formula milk commercially available in Lebanon: A novel approach based on feeding parameters versus toxicity

Infant formula milk (IFM) is increasingly utilized as a substitute for natural breastfeeding despite the fact that breast milk has been always recognized as the optimal nourishment method. While IFMs are fortified with essential nutrients that are crucial for proper growth, they can also harbor non-essential toxic metal contaminants from various sources during the production process. Given the heightened vulnerability of newborns to such contaminants, it is imperative to thoroughly analyze, evaluate, and minimize the toxicity associated with the consumption of such IFMs. However, classical approaches to date, have been always adopted for assessing such risks by finding first the analytical concentration of metals in the IFMs followed by multiplying it by the average daily powder intake (ADI) then dividing by the average infant weight. The outcome is then compared to an established standard such a PTWI to assess the extent of toxicity. The drawback with such studies is the use of a fixed ADI for all samples as if all samples have the same and exact preparation directions while using somewhat different infant masses.Accordingly, this study aims at assessing the toxic risk amongst newborns from IFM consumption through the identification and application of various highly important and toxicity-contributing parameters from each IFM and its directions of preparation label separately which are discussed here for the first time while providing comparisons between the classical approach versus our new approach to highlight its importance.Seventy-three IFMs (0–6 months) were analyzed for lead (Pb), cadmium (Cd), arsenic (As), and aluminum (Al) levels and unlike previous studies, this work incorporated various feeding parameters from each IFM for calculating the intakes thus, revealing potential toxicity risks even in IFMs that are considered safe by the classical approach. Metal contamination was significant, with 97.3 % of samples containing detectable Pb, 41.1 % Cd, 16.4 % As, and 93.2 % Al while highlighting Pb in exceeding its maximum allowable level (MAL). This novel approach, which considers new diverse feeding schedules/parameters that are ironically suggested by manufacturers that have been previously overlooked elsewhere, emphasized IFMs' potential as sources of heightened metal toxicity in comparison to classical approaches. Results highlighted Pb and Al as major concerns, with As and Cd of lesser concern. Findings also emphasized the importance of such new parameters for safeguarding newborn health and should be payed attention to by caregivers. The study strongly and highly recommends adherence to minimum feeding schedules (MFS) and proper scooping techniques to reduce newborn exposure to toxic metals. It also suggests continuous monitoring and stricter regulations by health authorities at the production level of such products so as to provide a safer commodity in the first degree and to also provide better and somewhat uniform and specific feeding labels and precautions on such products.

The particle effect: comparative toxicity of chlorpyrifos in combination with microplastics and phytoplankton particles in mussel

Lately, the role of microplastics (MP) as vectors for dissolved contaminants and as vehicle for their transfer to aquatic organisms has received attention. Similarly to MP, other inorganic and organic particles may act as passive samplers. However, limited comparative knowledge exists at this respect. In the present study we have comparatively investigated the risk for mussel of MP and the pesticide chlorpyrifos (CPF) alone and in combination with MP and phytoplankton particles of microalgae (MP-CPF and MA-CPF, respectively). We selected MP and microalgae of similar size to expose mussel to the same volume of particles (≈1.5 mm3L−1 ≈ equivalent to 1.5 mg MP L−1) and the same concentration of contaminant (CPF, 7.6 μg L−1). MP were virgin HDPE microparticles (≤10 μm) while the microalgae species was Isochrisis galbana (4–8 μm). Mussels were exposed for 21 days to MP, CPF, MP-CPF and MA-CPF. Then, a suite of neurotoxicity, oxidative stress and oxidative damage biomarkers were measured in samples collected at day 7 and 21. Additionally, these biochemical markers were assessed in an integrated manner with others measured at physiological, immune and cell component level in the same organisms, previously published. Overall, MP did not elicit significant alterations on the majority of parameters measured. In contrast, mussels exposed to CPF, MA-CPF and MP-CPF showed evidence of neurotoxicity and oxidant imbalance at day 7, added to a detrimental physiological condition and immune imbalance at day 21. At the latter time MP-CPF mussels showed greater alterations than CPF or MA-CPF mussels. This suggested a synergistic toxicity of MP combined with CPF greater than that produced by the contaminants alone (MP or CPF) or by MA combined with CPF.

Adjuvant immunotherapy in high-risk resectable melanoma: A real-world experience

Adjuvant immunotherapy with nivolumab or pembrolizumab represents the current standard of care for resected high-risk Stage III and IV malignant melanoma. However, data on its real-world outcomes and efficacy beyond clinical trials are limited. We evaluated the data of high-risk Stage III and IV melanoma patients treated with adjuvant immunotherapy in two hospitals in Western Australia, Australia. The study involved the retrospective collection and analysis of data from 95 eligible patients treated with nivolumab or pembrolizumab. These patients were planned to receive 1 year of immunotherapy, with treatment continuing until disease recurrence, unacceptable toxicity, or voluntary withdrawal. Our evaluation focused on overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS), along with safety outcomes. The findings of our study indicated a 2-year RFS of 73%, a DMFS of 73%, and an OS of 94%. Treatment-related adverse events were observed in 63.1% of patients, with cutaneous manifestations being the most common treatment-related toxicity and gastrointestinal tract issues being the most common higher-grade immune-related adverse event. Importantly, these findings do not significantly differ from the landmark clinical trials, CheckMate-238 and KEYNOTE-054. In conclusion, adjuvant immune checkpoint inhibitor therapy administered for up to 1 year in high-risk Stage III and IV melanoma demonstrates a comparable efficacy and toxicity profile in real-world settings to that observed in the pivotal trials.

Comparative Acute Toxicity Studies of Chlorpyrifos Technical Grade with its Emulsifiable Concentrate (20% EC) on Labeo rohita, a Freshwater Major Carp, and Mystus vittatus, a Freshwater Catfish.

Chlorpyrifos is widely used across the world as an organophosphate insecticide and frequently contaminates freshwater bodies through runoff from agricultural fields. In the laboratory, static bioassays were undertaken to examine differences in acute toxicity caused by exposure to the technical grade (94% a.i.) and an emulsifiable concentrate (20% EC) of chlorpyrifos to two species of freshwater fish, Labeo rohita and Mystus vittatus. The recovery of actual chlorpyrifos concentrations varied from 83% (technical grade, T) to 89% (emulsifiable concentrate, F) after two hours in water. The susceptibilities of the two fish species to the two types of chlorpyrifos varied. The 96-h LC50 values for T and F chlorpyrifos in L. rohita were 68 and 36µg/L, respectively, and 120 and 62µg/L in M. vittatus, respectively. As the exposure period was extended, the LC50 values gradually decreased. LC50 values between the technical grade and formulation were compared following the criteria of Mayer et al. (1986), Schmuck et al. (1994), APHA (1995), and Demetrio et al. (2014). It was concluded from the study that the emulsifiable concentrate (20% EC) of chlorpyrifos was more toxic than technical-grade chlorpyrifos.

Comparative toxicity assessment of alternative versus legacy PFAS: Implications for two primary trophic levels in freshwater ecosystems

Perfluoroalkyl substances (PFAS) are common environmental pollutants, but their toxicity framework remains elusive. This research focused on ten PFAS, evaluating their impacts on two ecotoxicologically relevant model organisms from distinct trophic levels: the crustacean Daphnia magna and the unicellular green alga Raphidocelis subcapitata. The results showed a greater sensitivity of R. subcapitata compared to D. magna. However, a 10-day follow-up to the 48 h immobilisation test in D. magna showed delayed mortality, underlining the limitations of relying on EC50 s from standard acute toxicity tests. Among the compounds scrutinized, Perfluorodecanoic acid (PFDA) was the most toxic to R. subcapitata, succeeded by Perfluorooctane sulfonate (PFOS), Perfluorobutanoic acid (PFBA), and Perfluorononanoic acid (PFNA), with the latter being the only one to show an algicidal effect. In the same species, assessment of binary mixtures of the compounds that demonstrated high toxicity in the single evaluation revealed either additive or antagonistic interactions. Remarkably, with an EC50 of 31 mg L-1, the short-chain compound PFBA, tested individually, exhibited toxicity levels akin to the notorious long-chain PFOS, and its harm to freshwater ecosystems cannot be ruled out. Despite mounting toxicological evidence and escalating environmental concentrations, PFBA has received little scientific attention and regulatory stewardship. It is strongly advisable that regulators re-evaluate its use to mitigate potential risks to the environmental and human health.

The oxidative stress-dependent pulmonary inflammation of inhalable multi-walled carbon nanotube-containing nano-concrete dust and its comparison with conventional concrete dust and DQ12

Nano-concrete, which is an admixture of nanomaterials in concrete recipes, has been investigated to overcome the limitations of existing concrete, such as its stability and strength. However, there is no information on the human health effects of broken-down dust released during the construction and demolition efforts. In this study, we prepared an inhalable fraction of multi-walled carbon nanotube-containing nano-concrete dust and performed comparative toxicity studies with conventional concrete dust and DQ12 using a rat intratracheal instillation model. Although the recipes for concrete and nano-concrete are entirely different, the pulverized dust samples showed similar physicochemical properties, such as 0.46–0.48 µm diameter and chemical composition. Both concrete and nano-concrete dust exhibited similar patterns and magnitudes, representing acute neutrophilic inflammation and chronic active inflammation with lymphocyte infiltration. The toxicity endpoints of the tested particles at both time points showed an excellent correlation with the reactive oxygen species levels released from the alveolar macrophages, highlighting that alveolar macrophages are the primary target cells and that the oxidative stress paradigm is the main toxicity mechanism of the tested particles. In addition, the toxicity potentials of both concrete and nano-concrete dust were more than 10 times lower than that of DQ12.

Synergistic toxic effects and mechanistic insights of beta-cypermethrin and pyraclostrobin exposure on hook snout carp (Opsariichthys bidens): A biochemical, transcriptional, and molecular approach

The extensive utilization of pesticides results in their frequent detection in aquatic environments, often as complex mixtures, posing risks to aquatic organisms. The hook snout carp (Opsariichthys bidens) serves as a valuable bioindicator for evaluating the impacts of environmental pollutants in aquatic ecosystems. However, few studies examined the toxic effects of pesticides on O.bidens, let alone the characterization of the combined effects resulting from their mixtures. This study aims to elucidate the toxic effects of beta-cypermethrin and pyraclostrobin on O.bidens, individually and in combination, focusing on biochemical, transcriptional, and molecular responses. By organizing and analyzing the toxicogenomic databases, both pesticides were identified as a contributor to processes such as apoptosis, oxidative stress, and inflammatory responses. The acute toxicity test revealed comparable acute toxicity of beta-cypermethrin and pyraclostrobin on O.bidens, with LC50 being 0.019 and 0.027 mg/L, respectively, whereas the LC50 decreased to 0.0057 and 0.0079 mg/L under the combined exposure, indicating potential synergistic effects. The activities of enzymes involved in oxidative stress and detoxification were significantly altered after exposure, with superoxide dismutase (SOD) and catalase (CAT) increasing, while malondialdehyde (MDA) levels decreased. The activity of CYP450s was significantly changed. Likewise, the expression levels of genes (mn-sod, p53, esr, il-8) associated with oxidative stress, apoptosis, endocrine and immune systems were significantly increased. Combined exposure to the pesticides significantly exacerbated the aforementioned biological processes in O.bidens. Furthermore, both pesticides can modify protein activity by binding to the surface of SOD molecules and altering protein conformation, contributing to the elevated enzyme activity. Through the investigation of the synergistic toxic effects of pesticides and molecular mechanisms in O.bidens, our findings highlight the importance of assessing the combined effects of pesticide mixtures in aquatic environments.

Investigating the Anticancer Potential of Zinc and Magnesium Alloys: From Base Materials to Nanocoated Titanium Implants.

In this work, we show the in vitro anticancer potential of surgical wires, obtained from zinc (ZnMg0.004) or magnesium (MgCa0.7) alloys by spatial technology comprising casting, extrusion, and final drawing processes. We also present the selective anticancer effects of applied soluble multilayer nanocoatings of zinc and magnesium onto titanium surfaces using the pulse laser deposition method. In the latter, the titanium samples were produced via 3D printing using the selective laser melting method and coated with various combinations of zinc and magnesium layers. For cytotoxicity studies, human dental pulp-derived stem cells (hDPSCs) and human osteosarcoma SaOS-2 cell line were used as representatives of healthy and cancer cells. Cells were examined against the 0.3-3.0 cm2/mL material extract ratios obtained from experimental and steel surgical wires, the latter being the current clinical industry standard. The MgCa0.7 alloy wires were approx. 1.5 times more toxic to cancer cells at all examined extract ratios vs. the extracts from steel surgical wires that exhibited comparable toxicity towards healthy and cancer cells. The ZnMg0.004 alloy wires displayed increased toxicity towards cancer cells with decreasing extract ratios. This was also reflected in the increased anticancer effectiveness, calculated based on the viability ratio of healthy cells to cancer cells, from 1.1 to 4.0 times. Healthy cell viability remained at 80-100%, whereas cancer cell survival fluctuated at 20-75%, depending on the extract ratio. Furthermore, the culture of normal or cancer cells on the surface of Zn/Mg-coated titanium allowed us to select combinations of specific coating layers that yielded a comparable anticancer effectiveness to that observed with the experimental wires that ranged between 2 and 3. Overall, this work not only demonstrates the substantial anticancer properties of the studied wires but also indicates that similar anticancer effects can be replicated with appropriate nanocoatings on titanium samples. We believe that this work lays the groundwork for the future potential development of the category of new implants endowed with anticancer properties.

Green and chemical synthesis of CuO nanoparticles: comparative reproductive toxicity evaluation at various phases and in offsprings

Metallic nanoparticles (NPs) are used in various biomedical applications due to their widespread utility. This study compares the reproductive toxicity of chemically synthesized CuO NPs (ChemSyn CuO NPs) and green synthesized CuO NPs (GrSyn CuO NPs) in rats and their offspring during mating, pregnancy, and lactation phases. CuO NPs were synthesized using Rhus punjabensis extract and their physio-morphological characteristics were illustrated. Both approaches showed pure and spherical NPs with an average size of 14.94 ± 0.6 and 19.02 ± 0.9 nm. Orally administered NPs at a dose of 100 mg kg−1 body weight of ChemSyn NPs reduced peroxidase activity by 38% and glutathione levels by 36%. In female rats treated with ChemSyn NPs, TBARS were increased by 11%, and total protein increased by 54%. The offspring did not show notable differences in their antioxidant status, but reactive substances in female offspring increased by 32%, and total protein content decreased by 57%. Genotoxicity of 2.72% and 1.9% tail DNA was observed in male and female pups, respectively. Testosterone levels were reduced in male parents, and progesterone concentration increased in female parents in a dose-dependent manner. In contrast, GrSyn NPs were more biocompatible, and thyroid hormones in the parents showed less variation. No obvious alterations were observed in the histological patterns of the gonads. These findings indicate that GrSyn NPs can be explored as drug carriers and contrast agents in vivo.