Toxic Effects Research Articles

Ophthalmic Complications Associated With the Antidiabetic Drugs Semaglutide and Tirzepatide.

Nearly 2% of the US population received a prescription for semaglutide in 2023. There has been a recent concern that this drug and other similar medications may be associated with ophthalmic complications. To report ophthalmic complications associated with the use of semaglutide or tirzepatide. This was a retrospective case series. All patients were initially seen in a community setting. Patients experiencing an ophthalmic complication in association with the use of semaglutide or tirzepatide were included in this analysis. Patients described were using either semaglutide or tirzepatide. Visual acuity and visual field defects. A total of 9 patients (mean [SD] age, 57.4 [11.6] years; age range, 37-77 years; 5 female [56%]; 4 male [44%]) were included in this study. Seven patients with nonarteritic ischemic anterior optic neuropathy, 1 patient with bilateral papillitis, and 1 patient with paracentral acute middle maculopathy were reported. Atypical features included sequential ischemic optic neuropathy, bilateral disc swelling at presentation, and progressive vision loss. In this case series study, it was not possible to determine if there is a causal link between these drugs and the ophthalmic complications reported. In some cases, it is hypothesized that rapid correction of hyperglycemia induced by these drugs, rather than a toxic effect of the drugs, could be associated with the ophthalmic complications reported.

Characteristics and Predictive Analysis of Heavy Metal Pollution in Typical Municipal Solid Waste Landfill Soil

ABSTRACT Due to the excavation of landfill sites, the safe disposal of high-content humus soil and the control of secondary heavy metal pollution have become urgent issues to be addressed. Exploring the forms of heavy metals in humus soil is crucial for a comprehensive and accurate assessment of the characteristics and toxic effects of heavy metal pollution. The present study analyzed the pollution characteristics and ecological risks of heavy metals in humus soils obtained from three typical municipal solid waste landfills in Zhejiang Province, China. The results indicated elevated concentrations of Cu, Zn, Cr, and Pb in the three landfills, with maximum concentrations reaching 5041, 6093, 2756, and 3576 mg/kg, respectively. The RAC (Risk Assessment Code) Risk Index and Potential Ecological Risk Index methods indicate that Cd in landfills has a high ecological risk and high bioavailability. Five machine learning models of Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), and Multi-Layer Perception (MLP) were employed to predict the concentrations of heavy metals. The RF model showed the best performance for predicting Cu with an average Area Under the Curve (AUC) of 0.99, while the MLP model performed the best for predicting the concentration of Hg. This study provides a scientific basis and practical guidance for the effective control and resource utilization of heavy metal pollution in landfill humus soil.

Human serum albumin microspheres synchronously loaded with ZIF-8 and triptolide (TP) for the treatment of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in most patients. Only 20% to 30% of patients can be treated with potentially curative surgical resection. Local therapies such as radioembolization and hepatic arterial perfusion may be a more effective treatment strategy. The active ingredients of natural plants have aroused wide interest in the treatment of tumors. Triptolide shows toxic effects on a variety of epithelioid carcinoma cells. However, there is currently a lack of suitable delivery system for the treatment of ICC. In this study, organometallic framework material ZIF-8 was chosen to load TP, and then encapsuled in HSA micro-nanoparticles for the perfusion treatment of ICC. The results of SEM, XRD, and FTIR showed that ZIF-8 nanoparticles were encapsuled in HSA micro-nanoparticles. ZIF-8 nanoparticles (57.89 ± 12.24%) and TP@ZIF-8/HSA (36.8 ± 4.71%) micro-nanoparticles could significantly inhibited proliferation of RBE cell. Also, TP@ZIF-8/HSA micro-nanoparticles of all groups exhibited favorable cytocompatibility to L929 cells and hemocompatibility. RT-qPCR and western blot showed that ZIF-8 and TP induced apoptosis in cancer cells through mitochondria-related pathways. The results demonstrated that TP@ZIF-8/HSA was a potential chemotherapy candidate for the treatment of ICC.

Four Neurotoxic Insecticides Impair Partner and Host Finding in the Parasitoid Leptopilina heterotoma and Bioactive Doses Can Be Taken up Via the Host

In modern agriculture, control of insect pests is achieved by using insecticides that can also have lethal and sublethal effects on beneficial non-target organisms. Here, we investigate acute toxicity and sublethal effects of four insecticides on the males’ sex pheromone response and the female host finding ability of the Drosophila parasitoid Leptopilina heterotoma. The nicotinic acetylcholine receptor antagonists acetamiprid, flupyradifurone and sulfoxaflor, as well as the acetylcholinesterase inhibitor dimethoate were applied topically as acetone solutions. Males treated with all four insecticides no longer preferred the female sex pheromone in a T-olfactometer. Duration of wing fanning, an element of the pheromone-mediated male courtship behavior, was also reduced by all four insecticides. The ability of females to orientate towards host-infested feeding substrate was not affected by acetamiprid in the tested dose range. However, treatment with dimethoate, flupyradifurone and sulfoxaflor resulted in the loss of the females’ preference for host odor. At the lowest doses interfering with olfactory abilities of L. heterotoma in this study (acetamiprid: 0.21 ng, dimethoate: 0.105 ng, flupyradifurone: 2.1 ng and sulfoxaflor: 0.21 ng), ≥ 90% of the wasps survive insecticide treatment. Male pheromone responses and female host finding were also disturbed in those L. heterotoma that had developed in D. melanogaster larvae reared on dimethoate-treated feeding medium at sublethal levels. Hence, doses of this insecticide sufficient to interfere with chemical orientation of L. heterotoma can be taken up by the parasitoid via the food chain.

The Toxic Effects of Environmental Domoic Acid Exposure on Humans and Marine Wildlife

Biotoxins produced by harmful algal blooms (HABs) are a substantial global threat to ocean and human health. Domoic acid (DA) is one such biotoxin whose negative impacts are forecasted to increase with climate change and coastal development. This manuscript serves as a review of DA toxicosis after environmental exposure in humans and wildlife, including an introduction to HAB toxins, the history of DA toxicosis, DA production, toxicokinetic properties of DA, susceptibility, clinical signs, DA detection methods and other diagnostic tests, time course of toxicosis, treatment, prognostics, and recommendations for future research. Additionally, we highlight the utility of California sea lions (CSLs; Zalophus californianus) as a model and sentinel of environmental DA exposure.

Association of echocardiographic radiomics-based features with cardiotoxicity effect in breast cancer patients from the CARDIOCARE project

Abstract Introduction Improvements in breast cancer (BC) treatment including chemotherapy have increased significantly the BC survivors. However, higher BC survival rates have been compromised by life-threatening collateral toxic effects. Effects such as cardiomyopathy and heart failure, described as cardiotoxicity, have become main causes of comorbidity and mortality, having a great impact on patients’ quality of life. Purpose Leverage radiomics-based analysis to explore innovative, non-invasive echocardiography biomarkers that can associate with cardiotoxicity. Method A cohort of 28 prospective patients (above 60 years old, 10 cardiotoxic) of the EU-funded CARDIOCARE project [1] undergoing cardiotoxic antineoplasmatic therapy was utilized to investigate potential association between imaging features calculated from the end diastolic (ED) and end systolic (ES) apical 4- and 2-chamber views and patients’ cardiotoxicity status as defined by the project's cardiologists using imaging data (Left Ventricle Ejection Fraction , Global Longitudinal Strain) and blood test markers (high sensitive Troponin I and Nt-pro-Bnp). Imaging data were collected at baseline visit (start of the treatment) and 3 months after. A pre-trained deep neural network [2] was initially utilized to automatically segment the myocardium (MY) and the left ventricle (LV) from the ED and ES 4- and 2-chamber static views both at baseline (T0) and 3-month follow-up (T1). More than 1500 imaging features were calculated from all images of the MY and LV using radiomics, a state-of-the-art technique to elicit hidden image patterns using histogram, shape and textural features. Apart from radiomics at T0 and T1, time-dependent features (delta-radiomics) were also provided as the relative change in radiomics values between T0 and T1, aiming to reveal potential changes at the MY and LV areas through treatment. Cardiotoxicity status was defined at T1. Results A univariate analysis using the Wilcoxon rank-sum test identified a subset of 40 radiomics features (20 delta-radiomics and 20 from T1) to be considered statistically significant (p-value<0.05) in differentiating cardiotoxic from non-cardiotoxic patients. Histogram and shape-based characteristics showed no association with cardiotoxicity status. Additionally, radiomics-based features at T0 were not statistically significant. All significant features corresponded to textural properties of the MY, indicating that the heterogeneity of the MY can be a significant factor for cardiotoxicity. 17 out of 20 T1 features were calculated from the 4-chamber view of the MY (19/20 from the ED). 15 delta-radiomics textural features were extracted from the 2-chamber view of the MY region at the ES. Conclusion Heterogeneity of the myocardium quantified by radiomics has potential diagnostic impact in assessing cardiotoxicity response, paving the way for the development of image-based risk stratification models for the early detection of cardiac toxicity.

Toxic effect of methanol: radiation and pathomorphological parallels

INTRODUCTION: Acute chemical poisoning with alcohol-containing products represents a pressing and socially significant health issue.OBJECTIVE: To analyze changes in the brain associated methanol poisoning and lung complications using to CT and traditional X-ray examination, observe how these changed evolve over time, and compare them with the pathomorphological findings.MATERIALS AND METHODS: Between 2017 and 2024, 80 patients aged 23 to 77 years (mean age: 44.2 years; men – 68; women – 12), were admitted to the Center for Acute Poisoning at the State Budgetary Institution «Research Institute of Emergency Medicine named after. I. I. Dzhanelidze» with signs of acute methanol poisoning. Of these, 45 patients died, and 35 were discharged. CT imaging of the brain was not performed in 13 deceased patients due to their extremely severe condition, as death occurrent within 2–3 hours to 24 hours of admission. CT was not conducted due to their stable condition, where no indications were present.RESULTS: CT was performed in 50 patients (in 62.5% of cases). Of these, 22 patients (44%) exhibited normal brain structures and parameters with no pathological changes; while 28 patients (56%) demonstrated pathological changes. These included diffuse edema in 17 (60.7%) and hemorrhagic complications in 9 (32.14%).CONCLUSION: In this study, diffuse brain edema, various types of hemorrhagic changes, and combination of hemorrhagic complications with diffuse edema. These radiological changes corresponded with the pathological findings observed during the forensic medical examination (FME). The data obtained can contribute to the refinement of diagnostic algorithms and the enhancement of medical care for methanol poisoning.

Safe use of fluoride-containing toothpastes for caries prevention in children

Relevance. Following environmental rehabilitation efforts in Chapayevsk, Samara Region, an increase in the prevalence and severity of dental caries has been observed, particularly among preschool-aged children.Objective. To evaluate the safety of fluoride use for preventing dental caries in children.Material and methods. A survey was conducted among 124 parents of children aged 5–6 years attending preschools and 361 adolescents aged 12 and 15 years, using the WHO questionnaire (2013). Responses regarding oral hygiene habits were analyzed. Fluoride ion concentrations were measured in drinking water using the potentiometric method (GOST 4386-89 S.6), in urine according to GOST 8.563-96, and in toothpastes following GOST 7983-2016. The availability and popularity of fluoride-containing toothpastes in pharmacies and supermarkets were also assessed. Statistical analysis was performed using IBM SPSS Statistics v.26 (IBM Corporation).Results. Over the past 15 years, the fluoride content in drinking water decreased from 0.78–0.91 mg/L to 0.49– 0.71 mg/L following the city’s environmental rehabilitation efforts, remaining suboptimal for caries prevention. Analysis of fluoride excretion via the kidneys indicated low overall fluoride intake from water, toothpaste, and food. A weak correlation was found between the DMFT (decayed, missing, and filled teeth) index and urinary fluoride levels (ρ = 0.35), as well as estimated systemic fluoride levels (ρ = 0.36). These results indicate low fluoride intake, eliminating concerns about toxic effects on health. An analysis of toothpaste preferences showed that the population primarily chooses fluoride-free toothpastes or those with fluoride levels below 1000 ppm. This trend is influenced by the product range available, low adherence to preventive dental care, and misinformation from online sources that often attribute negative effects to fluoridation or raise safety concerns. The actual fluoride content in toothpastes was found to be within acceptable technological limits.

The Impact of Mercury from Dental Amalgams on Pregnancy and Childhood: A Health and Risk Assessment Evaluation.

Mercury is a pervasive global pollutant, with primary anthropogenic sources including mining, industrial processes, and mercury-containing products such as dental amalgams. These sources release mercury into the environment, where it accumulates in ecosystems and enters the food chain, notably through bioamplification in marine life, posing a risk to human health. Dental amalgams, widely used for over a century, serve as a significant endogenous source of inorganic mercury. Studies have demonstrated that mercury vapor can be released from amalgams at room temperature due to material corrosion, potentially leading to chronic exposure. Pregnant women and children are particularly susceptible to mercury's toxic effects, with research linking prenatal mercury exposure to developmental delays, neurocognitive deficits, and conditions such as autism spectrum disorder. Moreover, the long-term accumulation of mercury in the body raises concerns about delayed health impacts in individuals exposed during childhood. Recent findings suggest even low levels of mercury exposure may contribute to kidney damage mediated by oxidative stress, highlighting the importance of monitoring mercury levels in vulnerable populations. Prenatal mercury transfer and postnatal exposure through breastfeeding further amplify the risks. This review critically assesses the health implications of mercury exposure from dental amalgams, focusing on its impact on pregnancy and childhood development. It underscores the need for updated regulatory measures to mitigate mercury-related risks and calls for further research to clarify the extent of mercury's long-term effects on human health.

Environmentally-Relevant Concentrations of Atrazine Had Minor Impacts on Gut Microbiota and Liver Metabolite in Juvenile Turtles.

Toxic effects of herbicide atrazine (ATR) have been evaluated in various aquatic organisms, but our understanding of its potential impacts in reptile species remains limited. In this study, the functional performances, and gut microbiota and liver metabolite alterations of ATR-exposed Mauremys sinensis juveniles were measured to evaluate its potential toxic effects in turtles. ATR exposure had no impact on the growth rate, but would allow turtles to right themselves more quickly. Despite having no difference in gut microbial diversity, the microbial composition was slightly changed after ATR exposure. For example, a few bacterial genera were shown to increase in exposed turtles (e.g., Turicibacter), or only observed in higher-concentration groups (e.g., Dialister, Alistipes, Delftia). Similarly, only a few identified liver metabolites were found to change significantly (e.g., decreased levels of arginine and N-acetylneuraminate; increased levels of glutathione and isomaltose in low-concentration exposure group) after ATR exposure. Overall, minor alterations in gut microbial composition and liver metabolite indicated that ATR exposure at environmentally-relevant concentrations only produced limited impacts in turtle species, although these alterations might have potentially adverse consequences on the long-term health of exposed turtles.

Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy.

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including Escherichia coli, Salmonella, and Listeria monocytogenes, along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME). These bacteria and their derivatives possess intrinsic properties that stimulate the immune system, enhancing both innate and adaptive immune responses to further amplify therapeutic effects. The ability of bacteria to naturally accumulate in hypoxic tumor regions and their versatility in genetic modifications allow for tailored drug delivery strategies that synergistically enhance the effectiveness of chemotherapy, immunotherapy, and targeted therapies. This review comprehensively examines the fundamental principles of bacterial therapy, focusing on the strategies employed for bacterial engineering, drug loading, and the use of bacteria and their derivatives in targeted tumor therapy. It also discusses the challenges faced in optimizing bacterial delivery systems, such as safety concerns, unintended immune responses, and scalability for clinical applications. By exploring these aspects, this review provides a theoretical framework for improving bacterial-based drug delivery systems, contributing to the development of more effective and personalized cancer treatments.

Microwave-assisted synthesis of dual responsive luminomagnetic rare earth metal ions (Nd3+, Dy3+) co-doped nanohydroxyapatite for biomedical applications.

The existing demand for the development of innovative multimodal imaging nanomaterial probes for biomedical applications stems from their unique combination of dual response modalities, i.e., photoluminescence (PL) and magnetic resonance imaging (MRI). In this study, for the first time, neodymium (Nd3+) and dysprosium (Dy3+) rare earth (RE) metal ions were co-doped into a hydroxyapatite (HAp) crystal lattice using a simple microwave-assisted synthesis technique to incorporate the essential properties of both the lanthanides in HAp. Theoretical as well as experimental studies were performed on novel Nd:Dy:HAp nanoparticles (NPs) to understand their photoluminescence and magnetic behaviour. Through co-precipitation, RE (Nd3+, Dy3+) ions were effectively integrated into the HAp crystal lattice, where they preferentially occupied the calcium ion (Ca2+) sites. The as-synthesized HAp, Nd:HAp, Dy:HAp, and Nd:Dy:HAp samples were characterized using different analytical tools. The PL and magnetic characteristics of Nd:Dy:HAp were dependent on the RE dopant ion type and concentration. In comparison with the pure HAp, the RE co-doped (Nd:Dy:HAp) NPs displayed multimodal features due to efficient energy transfer from the Nd3+ (sensitizer) to the Dy3+ (activator) ions. Furthermore, Nd:Dy:HAp NPs had good antimicrobial properties and they also displayed low cell toxicity effects. Hence, Nd:Dy:HAp NPs are attractive biomaterials for PL and MRI applications (e.g. permanent bone and tooth implants) and they can effectively be utilized in the biomedical industry for target-specific drug delivery, bioimaging, functional antimicrobial coatings etc. due to their tunable PL, magnetic, antimicrobial, and biocompatible capabilities.

Impact of microplastics on the human digestive system: From basic to clinical.

As a new type of pollutant, the harm caused by microplastics (MPs) to organisms has been the research focus. Recently, the proportion of MPs ingested through the digestive tract has gradually increased with the popularity of fast-food products, such as takeout. The damage to the digestive system has attracted increasing attention. We reviewed the literature regarding toxicity of MPs and observed that they have different effects on multiple organs of the digestive system. The mechanism may be related to the toxic effects of MPs themselves, interactions with various substances in the biological body, and participation in various signaling pathways to induce adverse reactions as a carrier of toxins to increase the time and amount of body absorption. Based on the toxicity mechanism of MPs, we propose specific suggestions to provide a theoretical reference for the government and relevant departments.

Mechanism of Ginkgo Diterpene Lactone Meglumine Injection Promoting Angiogenesis and Improving Cerebral Perfusion in Cerebral Infarction Rats

Background In recent years, traditional Chinese medicine has shown advantages in treating ischemic cerebrovascular diseases, including multi-component, multi-target, and low toxicity effects. Purpose: The aim of this study was to clarify the impact of ginkgo diterpene lactone meglumine injection (GDLMI) on promoting microvascular neovascularization and improving cerebral perfusion after cerebral infarction (CIF) in rats and to explore its underlying mechanisms in promoting angiogenesis. Methods Seventy-five rats were randomly rolled into Sham (sham surgery) group, Model (acute CIF model) group, low-dose (LD) (1 g/kg bw GDLMI) group, medium-dose (MD) (3 g/kg bw GDLMI) group, and high-dose (HD) (5 g/kg bw GDLMI) group. The neurological function of rats was evaluated using the Longa method. Micro-PET was performed to evaluate brain metabolism status at 7 days post-reperfusion. Serum expression levels (ELs) of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured. Brain tissue samples were collected to assess cerebral infarct volume and to measure oxidative stress (OS) markers, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). TdT-mediated dUTP nick end labeling (TUNEL) was performed to detect the apoptosis rate of cortical neurons. Western blotting was conducted to determine brain tissue’s ELs of vascular endothelial growth factor (VEGF), angiopoietins-1 (Ang-1), p-PI3K, and p-AKT proteins. Results Rats in Model group exhibited higher Longa scores and increased cerebral infarct volume, decreased brain 18F-FDG content, elevated serum ELs of IL-1β, IL-6, and TNF-α, reduced SOD and CAT activities, increased MDA content in brain tissue, elevated apoptosis rate of cortical neurons, and elevated protein ELs of VEGF and Ang-1 in brain tissue, accompanied by decreased ELs of p-PI3K and p-AKT proteins compared to the Sham group ( p < 0.05). Rats in the LD, MD, and HD groups showed decreased Longa scores and cerebral infarct volume, increased brain 18F-FDG content, decreased ELs of IL-1β, IL-6, and TNF-α, increased SOD and CAT activities, decreased MDA content in brain tissue, decreased apoptosis rate of cortical neurons, and increased protein ELs of VEGF, Ang-1, p-PI3K, and p-AKT in brain tissue versus Model group ( p < 0.05). The effects on all indicators in rats showed a dose-dependent trend. Conclusion GDLMI has a protective effect against acute CIF/reperfusion injury (RI), which may be attributed to its ability to suppress inflammation and OS damage by activating PI3K/AKT signaling.

Exploring the Chemical Complexity and Sources of Airborne Fine Particulate Matter in East Asia by Nontarget Analysis and Multivariate Modeling.

The complex and dynamic nature of airborne fine particulate matter (PM2.5) has hindered understanding of its chemical composition, sources, and toxic effects. In the first steps of a larger study, here, we aimed to elucidate relationships between source regions, ambient conditions, and the chemical composition in water extracts of PM2.5 samples (n = 85) collected over 16 months at an observatory in the Yellow Sea. In each extract, we quantified elements and major ions and profiled the complex mixtures of organic compounds by nontarget mass spectrometry. More than 50,000 nontarget features were detected, and by consensus of in silico tools, we assigned a molecular formula to 13,907 features. Oxygenated compounds were most prominent, followed by mixed nitrogenated/oxygenated compounds, organic sulfates, and sulfonates. Spectral matching enabled identification or structural annotation of 43 substances, and a workflow involving SIRIUS and MS-DIAL software enabled annotation of 74 unknown per- and polyfluoroalkyl substances with primary source regions in China and the Korean Peninsula. Multivariate modeling revealed seasonal variations in chemistry, attributable to the combination of warmer temperatures and maritime source regions in summer and to cooler temperatures and source regions of China in winter.

Case report: Dysphonia associated with high-dose cytarabine therapy

Cytarabine is widely used in the treatment of hematological malignancies. Its common toxicities include myelosuppression and gastrointestinal disturbances. Additionally, it can cause central nervous system (CNS) symptoms, which include hoarseness, ataxic tremor, ataxic gait, nystagmus, dysmetria, and dysdiadochokinesia. In this article, we present the first case report of dysphonia, absent of CNS symptoms, induced by high-dose cytarabine (HiDAC) in a patient with acute myeloid leukemia. The patient’s voice began to change 3 days following the first cycle of HiDAC chemotherapy, and dysphonia recurred upon the reintroduction of HiDAC. To rule out other potential causes, a thorough examination and detailed medical history review were conducted, excluding factors such as vocal abuse, infection, effects of other medications, and underlying diseases as contributors to the dysphonia. The patient was diagnosed with HiDAC-induced dysphonia. This toxic effect was self-limiting, and the patient recovered in 10–15 days. Chemotherapy-induced dysphonia is a rarely reported and easily overlooked side effect. This adverse reaction is typically temporary and non-life-threatening; however, it substantially diminishes quality of life and may occasionally necessitate the discontinuation or postponement of chemotherapy. Physicians should be aware of this complication when administering chemotherapeutic agents.

T-2 Toxin Nephrotoxicity: Toxic Effects, Mechanisms, Mitigations, and Future Perspectives.

T-2 toxin is a highly toxic fungal toxin that threatens humans and animals' health. As a major detoxifying and metabolic organ, the kidney is also a target of T-2 toxin. This article reviews T-2 toxin nephrotoxicity research progress, covering renal structure and function damage, nephrotoxicity mechanisms, and detoxification methods to future research directions. T-2 toxin damages kidney structure, causing renal dysfunction. The nephrotoxicity mechanism of T-2 toxin involves multiple factors including oxidative stress, endoplasmic reticulum stress, mitophagy, inflammatory responses, and apoptosis, which are intertwined and interdependent. Current detoxification strategies mainly involve reducing T-2 toxin in feedstuff and using antioxidant substances, but both have limits. Future research should focus on renal cells sensitivity to T-2 toxin, exploring key molecules in T-2 toxin's nephrotoxicity, renal injury's impact on other organs, and better detoxification methods. This review aims to guide future research and underpin T-2 toxin-induced nephrotoxicity prevention and treatment.

Effects of Lead Acetate Toxicity in Respect to Histological, Cytogenetical, Haematological Parameters and Subsequent Amelioration by Green Tea on Experimental Albino Rats

Lead acetate is arguably one of the environmental pollutants that threats the lives of living beings in multiple ways. Lead acetate occurs both naturally & due to human activities. Lead Acetate, a potential carcinogen, can enter the body through inhalation, ingestion, or dermal contact. Green tea and polyphenol have recently drawn attention of cell biologists. Multiple studies have confirmed the anti-inflammatory, anti-oxidative & anti-diabetic activities of polyphenols. In the Green tea extracts, Catechins including EGC (Epigallocatechin), ECG (Epicatechin-3-gallate), EGCG (Epigallocatechin-3-gallate) and EC (Epicatechin) are the major polyphenols which show a vast range of ameliorating effects on deleterious effects of different organs. Proper supplementation or dosage of green tea extracts may improve TAC (Total antioxidant capacity) and reduce the concentration of MDC (Malondialdehyde) in liver, brain and blood of vertebrates. Epicatechin supplementation could significantly lower the MDA levels and increase the glutathione concentration & catalase. It also increases superoxide dismutase (SODs, helpful antioxidant to defense against oxidative stress) & glutathione peroxidase activities in major organs. Though, high doses might have adverse effects, it has the capability to protect against oxidative damage & promote overall health. Twenty mature albino rats were used, divided into four groups of five rats per group. Group 1 (control male) were not administered with lead acetate or green tea extract; it received water only. Group 2 (male) was given lead acetate solution 0.003 ml/g; Group 3 (female) was administered with lead acetate 0.003 ml/g and Group 4 (male) was treated with lead acetate (0.003 ml/g) followed by green tea extract (0.0002 ml/g) daily. This study investigated the effect of lead acetate intoxication and ameliorating upshot of green tea extract on some haematological, histological, cytogenetical factors of Albino Rats.

Targeted editing of CCL5 with CRISPR-Cas9 nanoparticles enhances breast cancer immunotherapy.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Immunotherapy, a promising therapeutic approach, often faces challenges due to the immunosuppressive tumor microenvironment. This study explores the innovative use of CRISPR-Cas9 technology in conjunction with FCPCV nanoparticles to target and edit the C-C Motif Chemokine Ligand 5 (CCL5) gene, aiming to improve the efficacy of breast cancer immunotherapy. Single-cell RNA sequencing (scRNA-seq) and TCGA-BRCA data identified CCL5 as a key immune-related gene in breast cancer. Using CRISPR-Cas9, sgRNA targeting CCL5 was designed and delivered to breast cancer cells and humanized mouse models via FCPCV nanoparticles. In vitro experiments demonstrated that FCPCV nanoparticles effectively silenced CCL5, enhanced CD8+ T cell activity, and increased the production of cytokines such as IFN-γ, TNF-α, and GZMB. In vivo studies revealed significant tumor suppression, improved immune microenvironment, and increased CD8+/CD4+ ratios in treated mice, without notable toxic side effects. These findings highlight the potential of CRISPR-Cas9 nanoparticle-mediated gene editing as a novel strategy for enhancing breast cancer immunotherapy, providing a new direction for personalized and effective cancer treatment.

Polylactic Acid Micro/Nanoplastic Exposure Induces Male Reproductive Toxicity by Disrupting Spermatogenesis and Mitochondrial Dysfunction in Mice.

Although considered an "eco-friendly" biodegradable plastic, polylactic acid (PLA) microplastic (PLA-MP) poses a growing concern for human health, yet its effects on male reproductive function remain underexplored. This study investigated the reproductive toxicity of PLA in male mice and its potential mechanisms. To this end, our in vivo and in vitro experiments demonstrated that after degradation in the digestive system, a significant number of PLA-MP-derived nanoparticles could penetrate the blood-testis barrier (BTB) and localize within the spermatogenic microenvironment. Mice exposed to PLA-MPs for a long time exhibited significant reproductive toxicity, evidenced by decreased sperm concentration and motility, increased sperm deformity rates, and disrupted sex hormone levels. Further analysis revealed that PLA impaired BTB, induced mitochondrial dysfunction in the testes, and triggered oxidative stress through excessive ROS production from mitochondria, leading to further testicular damage. Notably, PLA nanoplastics internalized in the mitochondrial sheath and disrupted the mitochondrial structure of sperm, causing dose-dependent impairments in mitochondrial function. Transcriptome analyses further indicated that PLA-MPs disrupted spermatogenesis by inhibiting the expression of key mRNA involved in this process. Collectively, our findings highlight the reproductive toxic effect of biodegradable PLA by damaging BTB and impairing mitochondrial function, which provides insights into the toxicological implications of biodegradable microplastics for mammalian fertility.