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Urinary tract infections (UTIs) affect nearly 50% of women in their lifetime. Uropathogenic Escherichia coli (UPEC) expresses F9/Fml pili tipped with the protein FmlH that specifically bind to terminal galactoside and galactosaminoside units in glycoproteins on kidney and bladder cells and colonize host tissues. The traditional UTI treatment using excessive antibiotics has led to the rise in various UPEC antibiotic-resistant strains. An alternative therapeutic approach prevents the initial bacterial attachment on the host cells using competitive FmlH-binding inhibitors. In this study, we used computer-aided drug design techniques to identify novel glycomimetics that are predicted to bind strongly to and inhibit the UPEC FmlH. We performed in silico receptor-based and ligand-based scaffold hopping, and molecular docking to predict novel FmlH-binding glycomimetics with high chemical synthesizability. We replaced the two major scaffolds of the most potent known FmlH-binding ligand to obtain novel compounds. Additionally, we applied global machine-learning models to predict the ADMET properties of the molecules. Compounds with low ADMET risks were subjected to molecular dynamics simulations and a detailed investigation of the FmlH–glycomimetic interactions was performed. We have prepared and supplied a library of 58 novel glycomimetics that can be subjected to further biological activity studies. [ABSTRACT FROM AUTHOR]

Microplastics, particularly those in the micrometer scale, have been shown to enter the human body through ingestion, inhalation, and dermal contact. Recent research indicates that microplastics can potentially impact the central nervous system (CNS) by crossing the blood-brain barrier (BBB). However, the exact mechanisms of their transport, uptake, and subsequent toxicity at BBB remain unclear. In this study, we evaluated the size-dependent uptake and cytotoxicity of polystyrene microparticles using an engineered BBB model. Our findings demonstrate that 0.2 μm polystyrene microparticles exhibit significantly higher uptake and transendothelial transport compared to 1.0 μm polystyrene microparticles, leading to increased permeability and cellular damage. After 24 h of exposure, permeability increased by 15.6-fold for the 0.2 μm particles and 2-fold for the 1.0 μm particles compared to the control. After 72 h of exposure, permeability further increased by 27.3-fold for the 0.2 μm particles and a 4.5-fold for the 1.0 μm particles compared to the control. Notably, microplastics administration following TNF-α treatment resulted in enhanced absorption and greater BBB damage compared to non-stimulated conditions. Additionally, the size-dependent toxicity observed differently between 2D cultured cells and 3D BBB models, highlighting the importance of testing models in evaluating environmental toxicity. [ABSTRACT FROM AUTHOR]

The widely used non-steroidal anti-inflammatory drug, diclofenac, detected in increasing concentrations in freshwater ecosystems, is among the most pressing environmental problems today. In this study, the bacterial isolate Stenotrophomonas humi strain DIC_5 was capable of degrading diclofenac. It eliminated 75.1% of diclofenac at an initial concentration of 1.5 mg/L after 8 days in the presence of glucose (3.0 g/L). During the process, nitro-diclofenac was identified as a resulting metabolite, whose concentration increased significantly in the bacterial medium from the 7th day of the experiment, while the concentration of diclofenac decreased correspondingly. The ecotoxicological tests on Aliivibrio fischeri and zebrafish embryos showed that the bacterial metabolites without diclofenac have a higher toxicity (up to 35.5% bacterial bioluminescence inhibition and 36.7% embryo mortality) than the diclofenac degradation residues (28% and 26.7%, respectively). Based on these results, neither diclofenac nor its degradation products exhibit toxic effects on the test organisms. Conversely, the toxic effect caused by the bacteria was reduced in the presence of diclofenac. Our work highlights the importance of using biotic controls in biotransformation trials, especially when the foreign material is applied in intermediate or environmentally relevant concentration ranges. Key points: • Biotransformation of diclofenac by bacteria isolated from a bacterial biofilm. • Biotransformation of diclofenac led to the formation of nitro-diclofenac. • Microorganisms are alternatives for reducing the concentration of diclofenac in water. [ABSTRACT FROM AUTHOR]

Rapid industrialization, mining, and other anthropogenic activities have poisoned our environment with heavy metals, negatively impacting all forms of life. Heavy metal pollution causes physiological and neurological disorders, as heavy metals are endocrine disrupters, carcinogenic, and teratogenic. Therefore, it becomes mandatory to address the challenge of heavy metal contamination on a global scale. Physical and chemical approaches have been employed for pollutant removal and detoxification, but these methods cannot be adopted universally due to high cost, labor intensiveness, and possible negative impact on natural microflora. Phytoremediation is one of the preferred and safest approaches for environmental management due to its high efficiency and low cost of investment. The plant can uptake the pollutants and heavy metals from water and soil through an intense root network via rhizofiltration and process via phytostabilization, phytovolatilization, and accumulation. At a cellular level, the phytoremediation process relies on natural mechanisms of plant cells, e.g., absorption, transpiration, intracellular storage, and accumulation to counter the detrimental effects of pollutants. It is widely accepted because of its novelty, low cost, and high efficiency; however, the process is comparatively slower. In addition, plants can store pollutants for a long time but again become a challenge at the end of the life cycle. The current review summarizes phytoremediation as a potential cure for heavy metal pollutants, released from natural as well as anthropogenic sources. It will provide insight into the advancement and evolution of advanced techniques like nanoremediation that can improve the rate of phytoremediation, along with making it sustainable, cost‐effective, and economically viable. [ABSTRACT FROM AUTHOR]

AbstractThe process of microbial mineral precipitation has proven to be highly effective in addressing a wide range of pollutants in different environments. The objective of this study is to utilize the mineralization abilities of microbial strains found in the Noyyal River basin, which is home to a significant textile center in India, in order to both remove the color from reactive blue 4 and promote biomineralization. Promising results were obtained from the microbial isolates Streptomyces sp., Rhodococcus ruber, and Bacillus sp., and their consortium which demonstrated the ability to induce biomineralization and decolorize reactive blue 4. Characterization of the obtained biominerals through X-ray diffraction and FT-IR analysis showed the presence of well-crystallized polymorphs of calcium carbonate, along with other organic compounds. SEM-EDX analysis of biominerals formed during biomineralization-assisted decolourization of RB4 revealed distinct morphologies and elemental composition of the biominerals produced by microbial interactions with dye molecules. Further, to assess the safety and efficacy of these biominerals, zebrafish embryo toxicity tests were conducted by comparing biominerals produced during dye decolourization with the pure reactive blue 4 dye. Zebrafish embryos treated with biominerals exhibited normal developmental patterns, whereas those exposed to reactive blue 4 displayed mortality and abnormal hatching rates. The heart rates of the Zebrafish embryos were normal for controls and biomineral groups, but lower for RB4-exposed embryos. In conclusion, this study underscores the potential of biomineralization in remediating dye-contaminated wastewater, offering circular solutions for waste reduction and resource utilization. [ABSTRACT FROM AUTHOR]

AbstractAlpha-terpineol (α-T) is a type of monoterpenoid alcohol commonly present in essential oils, it contributes to a pleasant floral fragrance similar to that of lilacs. This research aimed to evaluate the impact of α-terpineol on the reproductive functions of both male and female rats, including gonadal activity, mating behavior, conception, conceptus development and parturition. Six male and female Wistar rats per group received α-terpineol through gavage at doses of 0, 75, 150 and 300 mg/kg/day. The study revealed changes in body weight gain inhibition, food consumption, azoospermia, decreased testosterone levels (0.7 ± 1.61 ng/mL, 0.7 ± 2.30 ng/mL) as well as histopathological variations in testis and epididymis among males exposed to doses of 150 and 300 mg/kg/day. Moreover, this exposure led to significantly decreased serum T4 levels in both adult males (21.85 ± 12.68 ng/mL, 16.20 ± 9.15 ng/mL) and dams (11.24 ± 12.37 ng/mL, 9.48 ± 11.74 ng/mL) at the dose range of 150 and 300 mg/kg/day without affecting TSH concentrations. In summary, the present study showed that α-terpineol induced reproductive toxicities in male rats. Therefore, a detailed toxicological assessment is highly recommended. [ABSTRACT FROM AUTHOR]

This review discusses the eco-friendly and cost-effective biosynthesis of gold nanoparticles (AuNPs) in viable microorganisms, focusing on microbes-mediated AuNP biosynthesis. This process suits agricultural, environmental, and biomedical applications, offering renewable, eco-friendly, non-toxic, sustainable, and time-efficient methods. Microorganisms are increasingly used in green technology, nanotechnology, and RNAi technology, but several microorganisms have not been fully identified and characterized. Bio-nanotechnology offers eco-friendly and sustainable solutions for nanomedicine, with microbe-mediated nanoparticle biosynthesis producing AuNPs with anti-oxidation activity, stability, and biocompatibility. Ultrasmall AuNPs offer rapid distribution, renal clearance, and enhanced permeability in biomedical applications. The review explores nano-size dependent biosynthesis of AuNPs by bacteria, fungi, and viruses revealing their non-toxic, non-genotoxic, and non-oxidative properties on human cells. AuNPs with varying sizes and shapes, from nitrate reductase enzymes, have shown potential as a promising nano-catalyst. The synthesized AuNPs, with negative charge capping molecules, have demonstrated antibacterial activity against drug-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii strains, and were non-toxic to Vero cell lines, indicating potential antibiotic resistance treatments. A green chemical method for the biosynthesis of AuNPs using reducing chloroauric acid and Rhizopus oryzae protein extract has been described, demonstrating excellent stability and strong catalytic activity. AuNPs are eco-friendly, non-toxic, and time-efficient, making them ideal for biomedical applications due to their antioxidant, antidiabetic, and antibacterial properties. In addition to the biomedical application, the review also highlights the role of microbially synthesized AuNPs in sustainable management of plant diseases, and environmental bioremediation. [ABSTRACT FROM AUTHOR]

Arsenic (As) in rice plants has toxic effects on their quality and human health. In the present study, 100 rice cultivars have been screened in hydroponics to analyze As toxicity and select As-tolerant and sensitive rice cultivars. The findings showed that rice cultivars responded differently to As stress at varying levels of effect. As treatments significantly changed morphological traits, the arsenic tolerance index (ATI %), pigments, and H2O2 concentrations. The rice cultivars Luit and Swarna demonstrated remarkable results (tolerant and sensitive) in terms of growth, as well as in terms of ATI, chlorophyll content, H2O2 content, and enzymatic and non-enzymatic antioxidants. Arsenic-induced pigment degradation and antioxidant content reduction were greater in Swarna than in Luit. Moreover, the results of biochemical analysis correlated with the morphological parameters. The selected As-tolerant and sensitive cultivars may be used to explore the tolerance mechanism in greater depth, which will require further molecular investigations. [ABSTRACT FROM AUTHOR]

Nano-pesticides have been created to substitute traditional pesticides and enhance agricultural techniques. The utilization of nano-pesticides poses a considerable obstacle due to the insufficiency of information regarding their prospective ecotoxicity, especially animal, human, and other non-target organism toxicity. This study was conducted to evaluate the toxicity of the nano-emulsion Lambda-cyhalothrin compared with the conventional one, depending on investigating the organ weight index and histopathological examination of vital organs in treated rats. There was no significant difference between the effects of conventional and nanoform of Lambda cyhalothrin on body weight index. Still, there was a significant elevation in the relative weight of the liver and kidney in conventional Lambda cyhalothrin and nano-treated rats. Histopathological results of conventional Lambda cyhalothrin-treated rats indicated marked vacuolar degenerated hepatocytes, hypercellularity in the glomeruli, vascular hemorrhage in the cerebral cortex, and vacuolization of Leydig cells. While nano Lambda cyhalothrin-treated rats showed hepatocytes with dilated and congested blood vessels and Kupffer cell activation, necrosis of some renal tubular epithelium, and intratubular mononuclear cell infiltration. The cerebral cortex showed some pyknotic Purkinje cells, and spermatogenic cells were decreased. [ABSTRACT FROM AUTHOR]

Introduction: Medicinal plants and their substances are used as adjunctive therapies for a range of acute and chronic inflammatory diseases. Syzygium aromaticum and Persea americana, in particular, have demonstrated beneficial effects, including anti-inflammatory and antioxidant properties, in the management of inflammation. Although the extracts from these plants have been assessed in research, the possibility of combining them to synthesise a mouthwash and evaluate its effectiveness has not yet been investigated. Aim: To evaluate the combined anti-inflammatory and antioxidant properties of a mouthwash formulation based on the extensively nutritious avocado fruit (Persea americana) and clove (Syzygium aromaticum). Materials and Methods: This in-vitro investigation was carried out in the Oral Pathology and Microbiology Department at Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India, between December 2021 and July 2022. A mouthwash was formulated with extracts from clove and avocado fruit, and its anti-inflammatory and antioxidant properties were evaluated using Bovine Serum Albumin (BSA) denaturation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, respectively. Microsoft Excel was utilised for data collection, and Statistical Package for the Social Sciences (SPSS) version 23.0 with independent t-tests was used for statistical analysis. A p-value of 0.05 was considered statistically significant. Results: The anti-inflammatory activity of the prepared mouthwash based on P. americana and Syzygium aromaticum at a concentration of 50 µL (86.62% inhibition) was comparable to that of the standard drug (diclofenac sodium) (84.82% inhibition); however, its antioxidant properties were significantly lower. Conclusion: The mouthwash synthesised from the edible part of P. americana in conjunction with Syzygium aromaticum exhibited superior anti-inflammatory properties, with the highest activity observed at a concentration of 50 µL. Therefore, the prepared formulation could be used for managing minor inflammatory conditions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the phytochemical content and toxicity profile of Rauwolfia vomitoria Afze (Apocynaceae). Method: Qualitative phytochemical screening of hydro-alcohol extract (HAE) of R. vomitoria roots was carried out followed by acute toxicity evaluation in nine Swiss albino Wistar rats using two phases of Lorke's method. In the 14 days subacute study, thirty-two Swiss albino rats were randomly divided into 4 groups of 8 rats each. Group A received 0.5 mL Tween 80 daily and served as control, while groups B, C and D was administered 125, 250 and 500 mg/kg/day of HAE respectively. All the rats were monitored daily for signs of toxicity. Selected haematological and biochemical parameters were assessed at the termination of experiment. Results: Alkaloids, cardiac glycosides, flavonoids and saponins were present in HAE. The estimated oral median lethal dose (LD50) was greater than 5000 mg/kg. Daily administration of HAE for 14 days resulted in 15.63 % mortality of animals across the groups by day 14 with significant loss in total body weight in group D animals on day 8 (p < 0.05), and in group C animals on day 11 (p < 0.05) and day 15 (p < 0.001). The dose of 500 mg/kg/day significantly (p < 0.05) increased haemoglobin concentration but reduced (p < 0.05) white blood cell count, while the dose of 250 mg/kg/day significantly (p < 0.05) reduced alkaline phosphatase levels but increased serum albumin levels (p < 0.05). Conclusion: Rauwolfia vomitoria may be safe on acute basis but repeated administration of high doses over many days needs to be done with caution. [ABSTRACT FROM AUTHOR]

Oral antimicrobials remain the mainstay of long-term treatment for many infections. Meanwhile, the use of oral agents is becoming commonplace for the treatment of several pediatric infections once managed exclusively with parenteral therapies. Unfortunately, antimicrobials are associated with several laboratory toxicities, particularly when high doses or combination therapies are used, but there is a paucity of data on optimal laboratory monitoring strategies. In this ID Consultant article, we offer a summary of the 3 most common laboratory-based toxicities seen with long-term use of oral antimicrobials—drug-induced kidney injury, liver injury, and hematological toxicities—and we provide our recommended approach to monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Although recent data suggest that melphalan high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT) is safe and effective in eligible multiple myeloma (MM) patients up to the age of 75 years, its value in elderly MM patients is still controversially discussed. Methods: We retrospectively analyzed 607 MM patients ≥60 years old, who were admitted to our institution for first-line or salvage HDT/ASCT between January 2007 and October 2018. We assigned them to three groups according to age at HDT/ASCT: 60–64 years (S1), 65–69 years (S2) and ≥70 years (S3). We compared progression-free and overall survival, duration of hospitalization, complications, transfers to intermediate or intensive care unit, readmissions after discharge and deaths within 100 days after HDT/ASCT between these groups. Results: Age did not impact progression-free and overall survival after first-line and salvage HDT/ASCT. Patients ≥70 years old at first HDT/ASCT had a longer hospitalization compared to patients 60–64 years old; however, the difference in the length of hospitalization was only marginal. Rates of febrile neutropenia, mucositis, transfers to intermediate or intensive care unit, readmissions after discharge, and deaths within 100 days after HDT/ASCT were similar in the 3 age groups of patients receiving first or salvage HDT/ASCT. Patients with a Charlson Comorbidity Index ≥2 receiving first HDT/ASCT had a higher risk for a transfer to intermediate or intensive care unit. Conclusion: Our analysis shows that HDT/ASCT is safe and effective in eligible elderly MM patients in first-line treatment and at relapse. A careful patient selection according to biological rather than chronological age is of crucial importance. [ABSTRACT FROM AUTHOR]

Increasing evidence shows that wild bees, including bumble bees, are in decline due to a range of stressors, including pesticides. Our knowledge of pesticide impacts has consequently grown to enable the design of increasingly realistic risk assessment methods. However, one area where knowledge gaps may still hinder our ability to assess the full range of bee‐pesticide interactions is the field of exposure. Exposure has historically been linked to either direct contact with pesticides or the ingestion of contaminated pollen and nectar by bees. However, bumble bees, and other wild bees, may also be exposed to pesticides while using contaminated soil as an overwintering substrate. Yet knowledge of how soil‐mediated exposure affects bumble bee health is lacking. Here we take one of the first steps towards addressing this knowledge gap by designing a method for testing the effects of soil‐mediated pesticide exposure on bumble bee queen hibernation success. We measured hibernation survival, body weight change and abdominal fat content and found that none of these responses were affected by a field realistic soil exposure to the novel insecticide cyantraniliprole. Our study may help in developing a standardised method to test the effects of the soil‐mediated pesticide exposure route in bumble bee queens. [ABSTRACT FROM AUTHOR]

Synthetic food antioxidants such as tert‐butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and propyl gallate (PG) have been extensively utilized in different food industries because of their high protectant activities to stop food spoilage and remove foodborne diseases in humans and animals. It would be emphasized that increasing the intake of antioxidants through intracellular may lead to cyto/genotoxicity, and their complex formation with biological molecules eventually accelerate the progress of various diseases like multiple sclerosis, diabetes, neurological disorders, cardiac vascular disease, cancer, etc. Therefore, their toxicity is one of the challenging subjects due to their extensive use in food‐related industries. TBHQ, BHA, and PG antioxidants have cytotoxic, genotoxic, and carcinogenic effects if absorbed in high doses through the gastrointestinal tract. Thermodynamic parameters presented that the hydrophobic bind plays a key role in the complexation of the TBHQ, BHA, and PG with albumin. The molecular modeling results showed that subdomain IIA plays a vital role in the interaction of TBHQ and BHA with albumin. To comprehend the mechanisms of the cyto/genotoxicity effects of these food antioxidants and conformational alterations of albumin macromolecule, we aim to overview numerous types of research that evaluated the cyto/genotoxicity effects of these antioxidants using several procedures. [ABSTRACT FROM AUTHOR]

The accumulation of heavy metals in soil and plant tissue is a serious concern since it impacts both soil quality and food safety. This study evaluated the accumulation of heavy metals and the food quality of lettuce as a result of the application of chemical fertilizer (CF) and bioslurry (BS). The treatments were CF (158 kg ha−1 NPS and 200 kg ha−1 urea), BS (5 ton ha−1), and control with no fertilizer, laid out in a randomized complete block design with three replications. Soil samples were analyzed for their physico‐chemical characteristics. The concentrations of 10 heavy metals (As, Pb, Zn, Cd, Cu, Ni, Co, Fe, Mn, and Cr) in the agricultural soil, bioslurry, and lettuce tissue were determined. Both the BS and CF reduced the concentrations of most heavy metals in the agricultural soil, particularly As, Pb, and Cd. Only the mean concentration of Cd in the agricultural soils exceeded the threshold level set by WHO/FAO (2011) for agricultural soils. Similarly, the concentration of As, Pb, and Cd in lettuce tissue grown in BS‐treated soils and the concentration of As in agricultural soils surpassed the limit set for vegetables. Given the toxicities of As, Cd, and Pb, as well as the effect on food safety, human health, and the environment, it is unsafe to cultivate lettuce using either the agricultural soil or BS in the study area. [ABSTRACT FROM AUTHOR]

Background: The safety of oral hygiene products is a growing concern, particularly regarding the toxicity of specific ingredients used in their formulations. The purpose of this study was to evaluate the knowledge and attitudes of dentists, physicians, pharmacists, and the general public regarding ingredients in oral hygiene products, especially fluoride. Additionally, this study aimed to identify which ingredients may exhibit potential toxicity based on historical records of any adverse effects being induced by a material/component. Methods: A self-administered questionnaire was used in an online cross-sectional observational study to collect data on sociodemographic characteristics, knowledge of fluoride in dental medicine, fluoride usage practices in oral hygiene products, opinions on ingredient toxicity in oral hygiene products, and personal experiences of adverse reactions to products and their components. The collected data underwent descriptive and regression analyses to reveal patterns and relationships within the dataset. Results: The study found a moderate overall knowledge level regarding fluoride usage in dentistry among participants (Md = 5.00, IQR 2.50–7.00). Healthcare professionals exhibited significantly higher knowledge scores compared to the general population (p ≤ 0.001), with dental professionals displaying the highest scores. Regarding concerns about the usage of fluoride, the majority of respondents (77.0%) did not express any concerns. Minor concerns included the risk of ingestion (6.0%) and dental fluorosis (4.6%). Among the other ingredients in oral hygiene products, respondents named alcohol as the most toxic ingredient (70.3%), followed by artificial colors (53.1%), artificial sweeteners (50.4%), and parabens (50.1%). It is noteworthy that the majority of participants (61.6%) stated that they had never experienced any side effects associated with the use of oral hygiene products. Conclusion: This study underscores disparities in fluoride knowledge between healthcare professionals and the general population in Croatia, with dental experts exhibiting a superior understanding. Despite lingering misconceptions about fluoride content and potential toxicity, the majority of participants acknowledge its oral health benefits and use fluoride products regularly. [ABSTRACT FROM AUTHOR]

Plants are a source of valuable organic chemical compounds with complex structures rich in therapeutic activities. The encapsulation of compounds in nanostructured systems is an alternative to avoid limitations, such as instability and low solubility, and to promote therapeutic use. The objective of the present review was to summarize the data in the literature on the physicochemical characteristics, biomedical efficacy, and toxicity of nanostructures containing extracts and oils obtained from annatto (Bixa orellana). For this, searches were conducted in the CINAHL, LILACS, Embase, FSTA, MEDLINE, ProQuest, PubMed, ScienceDirect, Scopus, and Web of Science databases. Studies that carried out the development, physical-chemical characterization, and evaluation of therapeutic efficacy and/or in vitro, in vivo, or clinical toxicity of nanostructures containing extracts and oils derived from annatto were included in the review. Of the 708 articles found, nine met the inclusion criteria. The included studies developed different nanostructures (nanofibers, nanocochleates, chitosan, lipid, polymeric, and metallic nanoparticles). These nanostructures showed leishmanicidal, photoprotective, antioxidant, antimicrobial, and immunomodulatory efficacy, and tissue regeneration potential with no or low toxic effects in the tested models. Thus, the present work supports the nanostructuring of annatto extracts and oils as a relevant approach to the development of new technologies for biomedical applications. [ABSTRACT FROM AUTHOR]

Background: The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein. Methods: Before its application in humans as a potential anticancer drug, C#1 was tested in animals to evaluate whether it could be administered to achieve a plasma concentration in vivo that inhibits cell proliferation in vitro without causing unwanted toxicity. To evaluate the efficacy and toxicity of C#1, a group of six intact female Beagle dogs was treated daily each morning for 90 days with an oral solution of C#1 in Soiae oleum emulgatum at a dose of 0.1 mg/kg body weight. During treatment, dogs were closely monitored clinically, and blood samples were taken to measure plasma C#1 concentrations, complete blood counts (CBC), clinical chemistry, and endocrinology. At the end of the treatment, dogs were euthanized for gross and histopathological analysis. An additional group of six female Beagle dogs was included for statistical reasons and only evaluated for efficacy during treatment for 30 days. Results: Daily administration of C#1 resulted in a constant mean plasma concentration of approximately 50 nmol/L. In both groups, two out of six dogs developed decreased appetite and food refusal after 4–5 weeks, and occasionally diarrhea. No significant effects in CBC or routine clinical chemistry were seen. Plasma IGF-1 concentrations, used as biomarkers for defective GHR signaling, significantly decreased by 31% over time. As plasma growth hormone (GH) concentrations decreased by 51% as well, no proof of GHR dysfunction could be established. The measured 43% decrease in plasma acylated/non-acylated ghrelin ratios will also lower plasma GH concentrations by reducing activation of the GH secretagogue receptor (GHSR). C#1 did not directly inhibit the GHSR in vivo, as shown in vitro. There were no significant effects on glucose, lipid, or folate/homocysteine metabolism. Conclusions: It is concluded that with daily dosing of 0.1 mg C#1/kg body weight, the induction of toxic effects prevented further increases in dosage. Due to the concomitant decrease in both IGF-1 and GH, in vivo inhibition of GHR could not be confirmed. Since the concept of specific inhibition of GHR synthesis by small molecules remains a promising strategy, searching for compounds similar to C#1 with lower toxicity should be worthwhile. [ABSTRACT FROM AUTHOR]

Herbicides are widely applied in agriculture, which results in the pollution of ecosystems, including inland waters. Herbicides present in water may cause pathological changes in fish. The aim of this study was to evaluate the effects of a clomazone-based herbicide formulation, Command 480 EC, on the haematological and blood biochemical parameters of common carp as well as the microstructure of selected organs: gills, liver and trunk kidney. The fish were exposed to Command 480 EC at a concentration corresponding to 1 or 5 mg/l of clomazone (groups COM1 and COM2, respectively) for 10 days. The conducted analyses showed that the treatment caused numerous changes in red blood cell parameters, no significant changes in WBC count (in comparison to the control), and only a few transient changes in the leukogram. The only significant change in the biochemical parameters in comparison to the control was a decrease in the triglyceride concentration in fish observed after 3 days (group COM1) and 10 days (group COM2) of exposure to this herbicide. No considerable histopathological alterations were observed. The results of the present study suggest that exposure to the applied clomazone-based formulation can cause pathophysiological changes in common carp. It was also observed that blood parameters (especially haematological ones) are more sensitive markers of exposure to Command than the microstructure of the tested organs. [ABSTRACT FROM AUTHOR]

Chemical composition of volcanic soils has been studied in the Southern Kuril Islands (Iturup, Kunashir, Shikotan), which undergo recurrently ash falls of mainly basic composition upon volcanic eruptions. The total content of metals (K, Ca, Mg, Na, Ba, Cu, Co, Cd, Cr, Fe, Mo, Ni, Pb, Sc, Sr, V, and Zn) and the concentrations of their mobile forms extracted by the ammonium acetate buffer at pH 4.80 have been determined. The total contents of Sc, V, Fe, and Zn are 1.5–5 times higher than their natural abundances in the upper layer of the Earth's crust (clarkes), whereas the contents of Cr, Ni, Sr, and Ba are 2–10 times lower. The soils show contrasting pH distribution (3.75–7.81) providing for the mobility of metals. The maximum activity of radial and lateral migration leading to radical differentiation of the genetic soil horizons by their chemical composition in different catenary positions is observed at low pH values; the coefficients of radial and lateral migration can rise up to 12 and 29, respectively. The results of factor analysis have revealed the leading role of soil-forming rocks in the formation of soil chemical composition (about 63% of sample variance); whereas humus formation, transformation of mineral and organic substances in soils, and hydrothermal activity exert a lesser effect. Soils formed on intermediate and mafic rocks of the Cenozoic volcanic massif are characterized by the Ca–Mg–Na paragenetic association; those formed on deposits of liparite–dacite complex are specified by the Ba–K–Pb–Mo association; on gabbroid rocks, by the Ni–Cr–Cu association; and on psammite, by the V–Sc–Fe–Co association. The Mo–Pb paragenesis is typical for the areas of current hydrothermal activity. The influence of placer formation on the chemical composition of soils in the coastal areas of Iturup and Shikotan Islands is shown. The distribution of mobile forms is associated with chelate-formation processes, geochemical barriers of acid–base, sorption, and redox types. Local soil pollution mainly related to the operation of motor vehicles has been identified. The areas of Krabozavodskoe and Yuzhno-Kuril'sk settlements show elevated concentrations of Ba, Sr and K due to the activities of fish processing plants; and the area of Kuril'sk city manifests elevated concentrations of Cr, Ni, Cu, Co, Zn and Pb, the source of which being the repair base. The calculated index of soil toxicity probability (MERMQ), as well as the results of biotesting for Daphnia magna and Chlorella vulgaris attest to the low soil toxicity. This is explained by the low population density and low economic development of the islands. [ABSTRACT FROM AUTHOR]

Objective: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH‐wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo‐angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib‐dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. Methods: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N‐Acetyl‐L‐Cysteine (NAC) might be used to reduce senescence‐associated adverse effects of axitinib treatment without altering its anti‐tumor activity. Results: We demonstrate that the use of the antioxidant molecule N‐Acetyl‐Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib‐dependent toxicity. Conclusion: Overall, we found that NAC co‐treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib‐dependent toxicity. [ABSTRACT FROM AUTHOR]

Over the past few years, numerous bacterial strains have become resistant to selected drugs from various therapeutic groups. A potential tool in the fight against these strains is antimicrobial photodynamic therapy (APDT). APDT acts in a non-specific manner by generating reactive oxygen species and radicals, thereby inducing multidimensional intracellular effects. Importantly, the chance that bacteria will develop defense mechanisms against APDT is considered to be low. In our research, we performed the synthesis and physicochemical characterization of curcumin derivatives enriched with morpholine motifs. The obtained compounds were assessed regarding photostability, singlet oxygen generation, aggregation, and acute toxicity toward prokaryotic Aliivibrio fischeri cells in the Microtox® test. The impact of the compounds on the survival of eukaryotic cells in the MTT assay was also tested (WM266-4, WM115—melanoma, MRC-5—lung fibroblasts, and PHDF—primary human dermal fibroblasts). Initial studies determining the photocytotoxicity, and thus the potential APDT usability, were conducted with the following microbial strains: Candida albicans, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. It was noted that the exposure of bacteria to LED light at 470 nm (fluence: 30 J/cm2) in the presence of quaternized curcumin derivatives at the conc. of 10 µM led to a reduction in Staphylococcus aureus survival of over 5.4 log. [ABSTRACT FROM AUTHOR]

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT's efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments. [ABSTRACT FROM AUTHOR]

Several studies with kaempferol (KP) and linearolactone (LL) have demonstrated their antiparasitic activity. However, the toxicity of these treatments is unknown. Therefore, this study aimed to evaluate the possible toxicological effects of intraperitoneal (i.p.) administration of KP or LL on the amoebic liver abscess model (ALA) in Mesocricetus auratus. An ALA was induced in male hamsters with 1.5 × 105Entamoeba histolytica (E. histolytica) trophozoites inoculated in the left hepatic lobe. The lesion evolved for 4 days, and then KP (5 mg/kg body weight/day) or LL (10 mg/kg body weight/day) was administered for 4 consecutive days. Then, magnetic resonance imaging (MRI), paraclinical analyses, and necropsy for histopathological evaluation were performed. There was similar ALA inhibition by KP (19.42%), LL (28.16%), and metronidazole, the antiamoebic control (20.87%) (p ≤ 0.05, analysis of variance [ANOVA]). There were hepatic and renal biochemical alterations in all treatment groups, mainly for KP (aspartate aminotransferase: 347.5 ± 37.5 U/L; blood urea nitrogen: 19.4 ± 1.9 g/dL; p ≤ 0.05, ANOVA). Lesions found in the organs were directly linked to the pathology. In conclusion, KP and LL decreased ALA development and exerted fewer toxicological effects compared with metronidazole. Therefore, both compounds exhibit therapeutic potential as an alternative treatment of amoebiasis caused by E. histolytica. However, additional clinical studies in different contexts are required to reaffirm this assertion. [ABSTRACT FROM AUTHOR]

The extensive use of polymeric materials has resulted in significant environmental pollution, prompting the need for a deeper understanding of their degradation processes and impacts. This review provides a comprehensive analysis of the degradation of polymeric materials in the environment and their impact on the health of experimental animals. It identifies common polymers, delineates their degradation pathways, and describes the resulting products under different environmental conditions. The review covers physical, chemical, and biological degradation mechanisms, highlighting the complex interplay of factors influencing these processes. Furthermore, it examines the health implications of degradation products, using experimental animals as proxies for assessing potential risks to human health. By synthesizing current research, the review focuses on studies related to small organisms (primarily rodents and invertebrates, supplemented by fish and mollusks) to explore the effects of polymer materials on living organisms and underscores the urgency of developing and implementing effective polymer waste management strategies. These strategies are crucial for mitigating the adverse environmental and health impacts of polymer degradation, thus promoting a more sustainable interaction between human activities and the natural environment. [ABSTRACT FROM AUTHOR]

Chlorpromazine (CPZ) is a first-generation neuroleptic with well-established antitumor and antiviral properties. Currently, numerous studies are focused on developing new methods for CPZ delivery; however, the knowledge regarding its conjugates with metal nanoparticles remains limited. The aim of this study was to prepare CPZ conjugates with gold nanoparticles (AuNPs) and evaluate their biological activity on human lymphocytes (HUT-78 and COLO 720L), as well as human (COLO 679) and murine (B16-F0) melanoma cells, in comparison to the effects induced by unconjugated CPZ molecules and AuNPs with well-defined properties. During the treatment of cells with CPZ, AuNPs, and CPZ-AuNP conjugates, changes in mitochondrial activity, membrane integrity, and the secretion of lipid peroxidation mediators were studied using standard biological assays such as MTT, LDH, and MDA assays. It was found that positively charged CPZ-AuNP conjugates more effectively reduced cell viability compared to AuNPs alone. The dose-dependent membrane damage was correlated with oxidative stress resulting from exposure to CPZ-AuNP conjugates. The activity of the conjugates depended on their composition and the size of the AuNPs. It was concluded that conjugating CPZ to AuNPs reduced its biological activity, while the cellular response to the treatment varied depending on the specific cell type. [ABSTRACT FROM AUTHOR]

Introduction: Naloxone is an effective antidote, but its short half-life means repeated doses, and infusions are often required. We investigated the effectiveness of adding intramuscular naloxone to titrated intravenous naloxone in opioid overdose in preventing recurrence of respiratory depression. Methods: This double-blinded randomised placebo-controlled trial was conducted in patients with suspected opioid poisoning and respiratory depression (respiratory rate <10 breaths/min or oxygen saturation <93%). Patients were randomised to receive either intramuscular naloxone 1,600 µg or saline placebo. All patients received titrated intravenous naloxone 100 µg and were managed on an opioid poisoning care pathway. The primary outcome was recurrence of respiratory depression within 4 h. Secondary outcomes were the proportion receiving naloxone infusions, number of naloxone boluses administered, reversal of respiratory depression at 10 min, and precipitation of opioid withdrawal (any symptom). Results: Recurrence of respiratory depression within 4 h was less common in 28/69 (41%) patients receiving intramuscular naloxone versus 48/67 (72%) patients receiving placebo (difference 31%, 95% CI: 13–46%; P < 0.001). Fewer naloxone infusions (5/69; 7% versus 25/67; 37%, difference 30%, 95% CI: 15 to 55%; P < 0.001) and fewer naloxone doses were administered (median 2, IQR: 1 to 5, versus median 5, IQR: 2 to 8; P = 0.001) in the intramuscular group. Reversal of respiratory depression at 10 min was similar between groups (51/69; 74% intramuscular naloxone versus 47/67; 70% placebo; P = 0.703). Opioid withdrawal occurred in 35/69 (51%) given intramuscular naloxone compared to 28/67 (42%) in the placebo group (difference 9%; 95% CI: −8 to 27%; P = 0.308). Discussion: The favourable pharmacokinetics of intramuscular naloxone, particularly its longer duration of activity, likely explains the improved effectiveness with lower recurrence of respiratory depression. Conclusion: The addition of intramuscular naloxone 1,600 µg to titrated intravenous naloxone prolonged effective reversal of respiratory depression, with fewer naloxone doses and infusions given, and no significant difference in patients developing withdrawal. [ABSTRACT FROM AUTHOR]

This study examined the concentrations of seven heavy metals (Pb, Cu, Zn, Cr, Cd, Ni, and Mn) in the muscle tissue of six commonly consumed fish species (Cyprinus carpio, Labeo rohita, Wallagu attu, Hypophthalmicthys molitrix, Channa punctuate, and Puntius sophore) from the River Indus in the Mianwali district Pakistan. Samples were collected during both pre-monsoon and post-monsoon seasons to assess the potential human health risks associated with these heavy metals. The levels of metals were measured using atomic absorption spectroscopic analysis. The results showed varying concentrations of heavy metals in the fish samples (mg/kg), ranging from 10.17-2.06 for Pb, 41.83-12.54 for Cu, 417.04-41.93 for Zn, 2.06-0.46 for Cr, 0.86-0.08 for Cd, 4.33-1.43 for Ni, and 50.16-8.74 for Mn. Notably, metal concentrations were generally higher during the pre-monsoon season, with Pb consistently exceeding standard limits in the muscle tissue of all fish species. ANOVA analysis revealed significant variations in heavy metal concentrations among different fish species. While the current consumption rate poses no significant health risks, ongoing monitoring of heavy metal concentrations in fish and their environmental sources is crucial to ensure consumer safety and sustainable aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Statins are widely used crucial drugs for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Although generally well tolerated, statin intolerance can unfortunately limit statin use, with statin-associated muscle symptoms (SAMS) being the most common side effect associated with its discontinuation. Statin intolerance is an inability to tolerate a dose of statin required to sufficiently reduce an individual's cardiovascular risk, limiting the effective treatment of patients at risk of or with cardiovascular disease (CVD). Statin myopathy is a broad entity encompassing self-limited/toxic and autoimmune aetiologies. As statins are a mainstay of therapy in those with or at risk for CVD and offer a mortality benefit, it is critical to determine whether one's symptoms are truly statin-associated before discontinuing the drug. This review article aims to provide an update on the epidemiology, pathophysiology, clinical features, diagnosis, evaluation and management of statin myopathy and to elucidate key differences between autoimmune and self-limited types. [ABSTRACT FROM AUTHOR]

We present our results on the synthesis and preliminary in silico and in vitro studies of the toxicology and antioxidant properties of selenylated analogs of Tacrine. Initially, we synthesized 2‐aminobenzonitriles containing an organic selenium moiety, resulting in sixteen compounds with various substituents linked to the portion derived from diorganyl diselenide. These compounds were then used as substrates in reactions with cyclic ketones, in the presence of 1.4 equivalents of trifluoroboroetherate as a Lewis acid, to synthesize selenylated analogs of Tacrine with yields ranging from 20 % to 87 %. In silico studies explored computational parameters related to antioxidant activity and hepatotoxicity. In vitro studies elucidated the antioxidant effects of Tacrine and its selenium hybrid (TSe) in neutralizing ABTS radicals, scavenging DPPH radicals, and reducing iron ions. Additionally, the acute oral toxicity of one synthesized compound was evaluated. [ABSTRACT FROM AUTHOR]

Polyurethane (PU) belongs to a unique class of polymers. Different properties of PU such as mechanical strength and biocompatibility can be enhanced by co-polymerizing it with different bio and synthetic polymers. It finds huge applications as micro-reactors for the fabrication of metal nanoparticles (MNPs) owing to the synergistic properties of both polyurethane and fabricated metal nanoparticles. Metal nanoparticles fabricated polyurethane have gained much attention in the last few years. These types of nanocomposites hyphenate the mechanical properties of polyurethane with the high surface-to-volume ratio of metal nanoparticles. Here, this review article briefly evaluates different methods of synthesis of polyurethane-based metal nanocomposites and their characterization via different techniques to evaluate their properties. Applications of these polyurethane based nanocomposite materials have also been described critically in different fields depending upon their catalytic, antimicrobial and antifungal potential. Future directions of these nanocomposite materials have also been described in the field of designing of nano-filters and nano-devices in order to attain environmental remediation and sustainability. [ABSTRACT FROM AUTHOR]

Thallium (Tl), a key element in high-tech industries, is recognized as a priority pollutant by the US EPA and EC. Tl accumulation threatens aquatic ecosystems. Despite its toxicity, little is known about its impact on cyanobacteria. This study explores the biochemical mechanisms of Tl(I) toxicity in cyanobacteria, focusing on physiology, metabolism, oxidative damage, and antioxidant responses. To this end, Anabaena and Nostoc were exposed to 400 µg/L, and 800 µg/L of Tl(I) over seven days. Anabaena showed superior Tl(I) accumulation with 7.8% removal at 400 µg/L and 9.5% at 800 µg/L, while Nostoc removed 2.2% and 7.4%, respectively. Tl(I) exposure significantly reduced the photosynthesis rate and function, more than in Nostoc. It also altered primary metabolism, increasing sugar levels and led to higher amino and fatty acids levels. While Tl(I) induced cellular damage in both species, Anabaena was less affected. Both species enhanced their antioxidant defense systems, with Anabaena showing a 175.6% increase in SOD levels under a high Tl(I) dose. This suggests that Anabaena's robust biosorption and antioxidant systems could be effective for Tl(I) removal. The study improves our understanding of Tl(I) toxicity, tolerance, and phycoremediation in cyanobacteria, aiding future bioremediation strategies. NOVELTY STATEMENT: This study presents novel insights into thallium (Tl) phycoremediation using Anabaena laxa and Nostoc muscorum, crucial for addressing the increasing contamination concerns stemming from high-tech industries. Elucidating the tolerance mechanisms and physiological responses of these cyanobacterial species to Tl(I) exposure. It highlights the potential of Anabaena laxa as an effective bio-remediator, offering a sustainable solution to mitigate Tl(I) environmental impact. [ABSTRACT FROM AUTHOR]

Thermal treatment of food can lead to the formation of potentially harmful chemicals, known as process contaminants. These are adventitious contaminants that are formed in food during processing and preparation. Various food processing techniques, such as heating, drying, grilling, and fermentation, can generate hazardous chemicals such as acrylamide (AA), advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), furan, polycyclic aromatic hydrocarbons (PAHs), N-nitroso compounds (NOCs), monochloropropane diols (MCPD) and their esters (MCPDE) which can be detrimental to human health. Despite efforts to prevent the formation of these compounds during processing, eliminating them is often challenging due to their unknown formation mechanisms. It is critical to identify the potential harm to human health in processed food and understand the mechanisms by which harmful compounds form during processing, as prolonged exposure to these toxic compounds can lead to health problems. Various mitigation strategies, such as the use of diverse pre- and post-processing treatments, product reformulation, additives, variable process conditions, and novel integrated processing techniques, have been proposed to control these food hazards. In this review, we summarize the formation and occurrence, the potential for harm to human health produced by process contaminants in food, and potential mitigation strategies to minimize their impact. [ABSTRACT FROM AUTHOR]

1. This study investigated the potential use of glycerol as a cryoprotectant for quail sperm cells. Its role in maintaining sperm fertilising ability in vivo and in vitro quality parameters, such as motility, was assessed. 2. The data showed that the presence of glycerol in semen samples was associated with infertility, which suggested that removal prior to insemination is mandatory. Removal through serial dilution centrifugation was associated with fewer than 5% of motile sperm cells and resulted in no fertility. 3. In conclusion, glycerol alone is not suitable for quail semen cryopreservation, and other approaches need to be investigated to develop cryobanking programmes for this species. [ABSTRACT FROM AUTHOR]

The transition to biofuels as viable alternatives to fossil fuels is increasingly critical, given the rising demand for sustainable energy. However, biofuel production is hindered by challenges such as feedstock scarcity, elevated production costs, and environmental impacts. Nanotechnology has the potential to significantly improve the efficiency and durability of biofuel production processes, thereby overcoming these challenges. Although there has been significant research on using nanomaterials in biofuel production, there needs to be more emphasis on understanding and addressing the difficulties of integrating these materials and developing strategies to overcome them. This review systematically examines the role of nanotechnology in various biofuel production pathways, including biodiesel, biogas, bioethanol, biohydrogen, hydrotreated vegetable oils, and Fischer–Tropsch synthesis. We discuss how nanomaterials improve key aspects of biofuel production, such as catalysis, microbial conversion, biomass pretreatment, and separation. Despite these advancements, nanotechnology has challenges, including nanoparticle toxicity, increased operational costs, and technical limitations. We propose potential solutions to these issues, emphasizing the need for interdisciplinary collaboration and innovative approaches. By effectively integrating nanotechnology into biofuel production, the energy sector can move toward a more sustainable and environmentally friendly future. [ABSTRACT FROM AUTHOR]

Introduction: Vortioxetine is an antidepressant with a multimodal mechanism of action. It is used as a treatment option for patients with major depressive episodes. There have only been two previously reported non-fatal overdoses of vortioxetine; neither of these were analytically confirmed There has also been one case of serotonin syndrome potentially related to vortioxetine and two deaths where vortioxetine was detected. We report here a non-fatal analytically confirmed case of vortioxetine overdose. Case report: A 32-year-old male presented to the emergency department (ED) 12–13 h after oral ingestion of 1,260 mg of vortioxetine and 350 mg of diazepam. A family member reported that he had been drowsy after the overdose, but his level of consciousness and observations (heart rate, blood pressure and temperature) were normal on review by the pre-hospital emergency services and on arrival to the ED. During a period of observation, he did not develop any features of serotonin syndrome or any other significant toxicity. Toxicological analysis of a blood sample taken in the ED detected vortioxetine (plasma concentration 457 ng/mL 10 h after ingestion) and sub-therapeutic concentrations of diazepam and pregabalin. Discussion: Despite having a plasma vortioxetine concentration nearly 15-times therapeutic vortioxetine concentrations, this patient did not develop any significant toxicity. In particular he did not develop any clinical or biochemical features of serotonin toxicity that would be expected with this class of antidepressant. Additional reporting of analytically confirmed vortioxetine overdoses will allow clinicians and licensing authorities to further understand the safety of this medication in overdose. [ABSTRACT FROM AUTHOR]

Purpose: Cyclophosphamide, Epirubicin/Doxorubicin, 5-fluorouracil (CEF or CAF) chemotherapy has long been a standard first-line treatment for breast cancer. The genetic variations of enzymes that are responsible for the metabolism of these drugs have been linked to altered treatment response and toxicity. Two drug-metabolizing enzymes ALDH1A1 and NQO1 are critically involved in the pathways of CEF/CAF metabolism. This study aimed to evaluate the effect of ALDH1A1 (rs13959) and NQO1 (rs1800566) polymorphisms on treatment response and toxicities caused by adjuvant (ACT) and neoadjuvant chemotherapy (NACT) where CEF/CAF combination was used to treat Bangladeshi breast cancer patients. Methods: A total of 330 patients were recruited from various hospitals, with 150 receiving neoadjuvant chemotherapy and 180 receiving adjuvant chemotherapy. To extract genomic DNA, a non-enzymatic simple salting out approach was adopted. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect genetic polymorphisms. Unconditional logistic regression was used to derive odds ratios (ORs) with 95% confidence intervals (CIs) to study the association between genetic polymorphisms and clinical outcome and toxicity. Results: A statistically significant association was observed between ALDH1A1 (rs13959) polymorphism and treatment response (TT vs. CC: aOR = 6.40, p = 0.007; recessive model: aOR = 6.38, p = 0.002; allele model: p = 0.032). Patients with the genotypes TT and CT + TT of the NQO1 (rs1800566) polymorphism had a significantly higher risk of toxicities such as anemia (aOR = 0.34, p = 0.006 and aOR = 0.58, p = 0.021), neutropenia (aOR = 0.42, p = 0.044 and aOR = 0.57, p = 0.027), leukopenia (aOR = 0.33, p = 0.010 and aOR = 0.46, p = 0.005), and gastrointestinal toxicity (aOR = 0.30, p = 0.02 and aOR = 0.38, p = 0.006) when compared to the wild CC genotype, while patients with the genotype CT had a significant association with gastrointestinal toxicity (aOR = 0.42, p = 0.02) and leukopenia (aOR = 0.52, p = 0.010). The TT and CT + TT genotypes of rs13959 had a significantly higher risk of anemia (aOR = 2.00, p = 0.037 and aOR = 1.68, p = 0.029). There was no significant association between rs1800566 polymorphism and treatment response. Conclusion: Polymorphisms in ALDH1A1 (rs13959) and NQO1 (rs1800566) may be useful in predicting the probability of treatment response and adverse effects from CEF or CAF-based chemotherapy in breast cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and cytotoxicity of experimental 6% and 35% hydrogen peroxide gels (HP6 or HP35) incorporated with titanium dioxide nanoparticles (NP) co-doped with nitrogen and fluorine and irradiated with a violet LED light (LT). Methods: Bovine enamel-dentin disks adapted to artificial pulp chambers were randomly assigned to bleaching (n = 8/group): NC (negative control), NP, HP6, HP6 + LT, HP6 + NP, HP6 + NP + LT, HP35, HP35 + LT, HP35 + NP, HP35 + NP + LT, and commercial HP35 (COM). Color (ΔE00) and whiteness index (ΔWID) changes were measured before and 14 days after bleaching. The extracts (culture medium + diffused gel components) collected after the first session were applied to odontoblast-like MDPC-23 cells, which were assessed concerning their viability, oxidative stress, and morphology. The amount of HP diffused through the disks was determined. Data were analyzed by generalized linear models or Kruskal Wallis Tests (α = 5%). Results: HP6 + NP + LT exhibited ΔE00 and ΔWID higher than HP6 (p < 0.05) and similar to all HP35 groups. HP6 + NP + LT showed the lowest HP diffusion, and the highest cell viability (%) among bleached groups, preserving cell morphology and number of living cells similar to NC and NP. HP6 + LT, HP6 + NP, and HP6 + NP + LT exhibited the lowest cell oxidative stress among bleached groups (p < 0.05). HP35, HP35 + LT, and HP35 (COM) displayed the lowest cell viability. Conclusion: HP6 achieved significantly higher color and whiteness index changes when incorporated with nanoparticles and light-irradiated and caused lower cytotoxicity than HP35 gels. The nanoparticles significantly increased cell viability and reduced the hydrogen peroxide diffusion and oxidative stress, regardless of HP concentration. Clinical Significance: Incorporation of co-doped titanium dioxide nanoparticles combined with violet irradiation within the HP6 gel could promote a higher perceivable and acceptable efficacy than HP6 alone, potentially reaching the optimal esthetic outcomes rendered by HP35. This approach also holds the promise of reducing cytotoxic damages and, consequently, tooth sensitivity. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. Objectives: To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. Search Strategy: In this meta‐analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. Selection Criteria: Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. Data Collection and Analysis: Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I2) was used to assess heterogeneity. Egger's regression test with a two‐tailed P value was used to evaluate publication bias. Main Results: Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76–9.20] and OR 4.71 [95% CI: 1.51–14.70], respectively). Conclusions: The bevacizumab‐containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab‐associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits. Synopsis: Bevacizumab induces higher risks of gastrointestinal/genitourinary toxicities in irradiated cervical cancer patients. Discussing the pros and cons of bevacizumab with the patient is essential. [ABSTRACT FROM AUTHOR]

Purpose: Patients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT). Methods: Between September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2–74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients. Results: Median follow-up time was 4.2 (0.15–9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent. Conclusion: IMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity. [ABSTRACT FROM AUTHOR]

Sulfur dioxide (SO2) are a category of chemical compounds widely used as additives in food industry. So far, the use of SO2 in fruit and vegetable industry has been indispensable although its safety concerns have been controversial. This article comprehensively reviews the chemical interactions of SO2 with the components of fruit and vegetable products, elaborates its mechanism of antimicrobial, anti-browning, and antioxidation, discusses its roles in regulation of sulfur metabolism, reactive oxygen species (ROS)/redox, resistance induction, and quality maintenance in fruits and vegetables, summarizes the application technology of SO2 and its safety in human (absorption, metabolism, toxicity, regulation), and emphasizes the intrinsic metabolism of SO2 and its consequences for the postharvest physiology and safety of fresh fruits and vegetables. In order to fully understand the benefits and risks of SO2, more research is needed to evaluate the molecular mechanisms of SO2 metabolism in the cells and tissues of fruits and vegetables, and to uncover the interaction mechanisms between SO2 and the components of fruits and vegetables as well as the efficacy and safety of bound SO2. This review has important guiding significance for adjusting an applicable definition of maximum residue limit of SO2 in food. [ABSTRACT FROM AUTHOR]

Seaweed endophytes are a rich source of microbial diversity and bioactive compounds. This review provides a comprehensive analysis of the microbial diversity associated with seaweeds and their interaction between them. These diverse bacteria and fungi have distinct metabolic pathways, which result in the synthesis of bioactive compounds with potential applications in a variety of health fields. We examine many types of seaweed-associated microorganisms, their bioactive metabolites, and their potential role in cancer treatment using a comprehensive literature review. By incorporating recent findings, we hope to highlight the importance of seaweed endophytes as a prospective source of novel anticancer drugs and promote additional studies in this area. We also investigate the pharmacokinetic and pharmacodynamic profiles of these bioactive compounds because understanding their absorption, distribution, metabolism, excretion (ADMET), and toxicity profiles is critical for developing bioactive compounds with anticancer potential into effective cancer drugs. This knowledge ensures the safety and efficacy of proposed medications prior to clinical trials. This study not only provides promise for novel and more effective treatments for cancer with fewer side effects, but it also emphasizes the necessity of sustainable harvesting procedures and ethical considerations for protecting the delicate marine ecology during bioprospecting activities. [ABSTRACT FROM AUTHOR]

A 14-day rat study with plasma metabolomics was conducted to evaluate the toxicity of Benzene. Wistar rats were orally administered Benzene daily at doses of 0, 300 and 1000 mg/kg bw. The study identified liver and kidneys as target organs of Benzene toxicity and found reductions in total white blood cells, absolute lymphocyte and eosinophil cell counts, and increased relative monocyte counts suggesting bone marrow as a target organ. The study also confirmed liver as a target organ using metabolomics, which showed indications of a stress reaction in rats and changes in metabolites suggestive of a metabolic disorder. The metabolomics investigations did not find any other toxicologically relevant modes of action, and the observed metabolite changes were not associated with markers for mitochondrial dysfunction. The study concludes that integration of omics technologies, such as metabolomics, in regulatory toxicity studies is possible, confirms existing knowledge and adds additional information that can be used for mechanistic understanding of observed toxicity. • Target organs after 14-day exposure to benzene are liver, kidney, bone marrow. • Metabolomics and toxicity parameters sufficient to identify subchronic toxicity. • Metabolomics indicates stress reaction and metabolic disorder in rats. • "smart" in vivo studies are a NAM that can reduce the need for subchronic in vivo testing. [ABSTRACT FROM AUTHOR]

Since ancient times, people have used medicinal plants to treat various diseases. Nerium oleander is a toxic plant due to the presence of various cardiac glycosides. Oleander, at a dose of 50 mg kg-1 inhibits Na+/K+ ATPase pump in mice. Despite being toxic, it is used in traditional medicine. Almost all of the parts of oleander plant contain various phytochemicals such as phenols, tannins, flavonoids, coumarins, sterols, triterpenes, alkaloids, and different types of cardenolides. Oleander extract has neuroprotective, sedative, and anticonvulsant properties, especially against ischemic stroke. Cardenolides like nerizoside, neritaloside, odoroside-H, and neridiginoside offer advantages when used as CNS depressants. CNS depressant action of oleander is primarily due to a rise in GABA levels. At low to moderate dose, it shows depressant activity but in high doses, body became motionless inducing tremors and lethargy. Oleanderʼs dual role of toxic and therapeutic activity raises concerns about its application. Yet due to presence of vast constituents, it can be used for modern medicine. Cardenolides showing antidepressant activity on mice. [Display omitted] • Nerium oleander is considered to be a poisonous plant. • But it contains various phytochemicals, including antioxidants, anticancer agents, CNS depressants, and anticonvulsants. • This review aims to identify the therapeutic benefits of the plant and its toxicity. [ABSTRACT FROM AUTHOR]

The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H 2 S) play important roles not only in maintaining physiological functions, but also in pathological conditions and events. Importantly, these molecules show a complex interplay in cancer biology, demonstrating both tumor-promoting and anti-tumor activities depending on their concentration, flux, and the environmental redox state. Additionally, various cell types respond differently to NO and H 2 S. These gasotransmitters can be synergistically combined with traditional anticancer treatments such as radiotherapy, immunotherapy, chemotherapy, and phototherapy. Notably, NO, and more recently H 2 S, have been shown to reverse multidrug resistance. Nanomaterials to deliver NO donors and, to a lesser extent, H 2 S donors, have emerged as a promising approach for targeted delivery of these gasotransmitters. Nanotechnology has advanced the delivery of anticancer drugs, enhancing efficiency and reducing side effects on non-cancerous cells. This review highlights recent progress in the design of NO and H 2 S-releasing nanomaterials for anticancer effects. It also explores the interactions between NO and H 2 S, which are crucial for developing combined therapies and nanomedicines with minimal side effects. • This review integrates recent nitric oxide (NO) and hydrogen sulfide (H 2 S) releasing nanomaterials in cancer treatment. • Research gaps are identified where further contributions can enhance understanding of the physiological roles of NO and H 2 S. • Gaps are explored throughout, highlighting potential avenues for exploration in cancer treatment using NO and H 2 S. [ABSTRACT FROM AUTHOR]

The presence of pharmaceuticals such as the antibiotic cephalexin in aqueous environments increases public health concerns due to their adverse biological effects and antibiotic resistance. It may be promising to remove these compounds from the aquatic environment through degradation reactions that convert them into non-toxic products. For this purpose, Density Functional Theory (DFT) molecular orbital calculations were performed to investigate the kinetics and mechanism of the degradation reaction of cephalexin with the hydroxyl (OH) radical. Reaction rate constants and branching ratios for 11 different reaction paths were calculated in the temperature range of 200 to 400 K. The total rate constant was calculated as 7.05 × 109 M−1 s−1 and is in good agreement with the experimental value. According to the kinetic and thermodynamic results, it can be concluded that the hydroxyl radical preferentially attacks the beta-lactam ring. The effect of water on the reaction mechanism was investigated in both implicit and explicit solvation models. Explicitly added water molecules affect the degradation reaction kinetic so that the results become compatible with the experimental ones. Ecotoxicity and bioaccumulation calculations on cephalexin and its degradation products show that some of its degradation products are harmful. [ABSTRACT FROM AUTHOR]

Recently, the multidisciplinary field of nanotechnology has garnered significant interest due to its diverse applications. Among the contemporary branches of nanotechnology, DNA nanobiotechnology has emerged as a captivating area of study, combining the principles of nanotechnology with oligonucleotides. This innovative science employs a variety of nucleotide structures, including aptamers, siRNAs, antisense oligonucleotides, and others. In this investigation, we conducted a comprehensive review of the hazards and challenges associated with DNA nanobiotechnology. Despite the numerous advantages of DNA and RNA oligonucleotides, their utilization may elicit adverse effects in plants and animals. Our literature review revealed that these oligonucleotides can trigger a range of detrimental reactions, such as intense immune system stimulation, induction of cell death, pro-inflammatory responses, vascular damage, kidney damage, anticoagulant effects, inhibition of bone marrow hematopoiesis, prevention of protein synthesis, alteration of gene expression, allergic reactions, leukopenia, hyperplasia, tissue accumulation, development of new toxins and allergens, emergence of antibiotic-resistant strains, and challenges pertinent to the food industry. Given the findings of our review, it is crucial for researchers to not only focus on the positive aspects of DNA nanobiotechnology but also to consider the potential negative consequences of this scientific domain. [ABSTRACT FROM AUTHOR]

Background: Ponatinib is a third‐generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with robust activity in Philadelphia chromosome–positive leukemias. Herein, we report the long‐term follow‐up of the phase 2 trial of ponatinib in chronic myeloid leukemia in chronic phase. Methods: Patients received ponatinib 30 to 45 mg/day. The primary end point was the rate of 6‐month complete cytogenetic response (CCyR). The study was held in June 2014 because of the risk of cardiovascular toxicity, requiring patients to change TKI. Results: Fifty‐one patients were treated with ponatinib (median dose, 45 mg/day). Median age was 48 years (range, 21–75); 30 (59%) had baseline cardiovascular comorbidities. Median treatment duration was 13 months (range, 2–25). Fourteen patients (28%) discontinued ponatinib because of toxicities, 36 (71%) after the Food and Drug Administration warning/study closure, and one for noncompliance. Dasatinib was the most frequently chosen second‐line TKI (n = 34; 66%). Among 46 patients evaluable at 6 months, 44 (96%) achieved CCyR, 37 (80%) major molecular response, 28 (61%) MR4, and 21 (46%) MR4.5. The cumulative 6‐month rates of CCyR, major molecular response, MR4, and MR4.5 were 96%, 78%, 50%, and 36%, respectively. Durable MR4 ≥24 or ≥60 months was observed in 67% and 51% of patients, respectively. The 24‐month event‐free survival rate was 97%. After a median follow‐up of 128 months, the 10‐year overall survival rate was 90%. Eight patients (16%) had serious grade 2 to 3 cardiovascular adverse events, leading to permanent discontinuation in five (10%). Conclusion: Ponatinib yielded high cytogenetic and molecular responses in newly diagnosed chronic myeloid leukemia in chronic phase. Its use in the frontline setting is hindered by arterio‐/vaso‐occlusive and other severe toxicities. Treatment with ponatinib in the frontline setting of chronic myeloid leukemia in chronic phase was associated with high molecular response rates, with 12‐month cumulative rates of major molecular response and MR4 of 82% and 72%, respectively. However, it was associated with an increased incidence of toxicity, in particular serious grade 2‐3 cardiovascular adverse events in 16% of the patients. [ABSTRACT FROM AUTHOR]

Nanotechnology is an emerging branch of science that incorporates the nanomaterials recognized as nanoparticles ranging from 1–100 nm in size. This technology is being used in the food industry, pharmaceutical industry, agricultural industry, medical treatments, environmental science, biological research, and aquaculture industry. Increasing disease susceptibility, pathogenic emergence and divergence, less efficient vaccines, probiotics, and ineffective antibiotics forced us to seek an alternative approach to tackle these challenges. Nanotechnology can change our views, perceptions, and perspectives, as it has provided us with a necessary tool to address these challenges. This technology has revolutionized aspects of providing solutions to many hazardous issues like disease control, nutrient delivery, water purification, vaccines, and drug delivery in aquaculture using nanoparticles. Several nanoparticles have been used as growth promoters, e.g., zinc, iron, and selenium nanoparticles. Many of them have antibacterial properties, e.g., silver and copper nanoparticles. Besides that, these nanoparticles have few toxicological effects, when they are used without proper knowledge and lead to unrealistic results. Therefore, there should be complete information and standard observation regarding their administration (e.g., time, dosage, exposure, and concentration), and certain parameters (temperature, pH, and salinity) should also noted before their use in aquaculture. This review aims to critically analyze and thoroughly discuss the meta-role of various nanoparticles regarding disease control, drug delivery, water treatment, nutrition, and growth performance as well as their toxicological impacts in fish aquaculture. [ABSTRACT FROM AUTHOR]