Toxic Effects Research Articles

A comparison of different machine learning classifiers in predicting xerostomia and sticky saliva due to head and neck radiotherapy using a multi-objective, multimodal radiomics model.

Background and Purpose. Although radiotherapy techniques are a primary treatment for head and neck cancer (HNC), they are still associated with substantial toxicity and side effects. Machine learning (ML) based radiomics models for predicting toxicity mostly rely on features extracted from pre-treatment imaging data. This study aims to compare different models in predicting radiation-induced xerostomia and sticky saliva in both early and late stages HNC patients using CT and MRI image features along with demographics and dosimetric information.Materials and Methods.A cohort of 85 HNC patients who underwent radiation treatment was evaluated. We built different ML-based classifiers to build a multi-objective, multimodal radiomics model by extracting 346 different features from patient data. The models were trained and tested for prediction, utilizing Relief feature selection method and eight classifiers consisting eXtreme Gradient Boosting (XGBoost), Multilayer Perceptron (MLP), Support Vector Machines (SVM), Random Forest (RF), K-Nearest Neighbor (KNN), Naive Bayes (NB), Logistic Regression (LR), and Decision Tree (DT). The performance of the models was evaluated using sensitivity, specificity, area under the curve (AUC), and accuracy metrics.Results.Using a combination of demographics, dosimetric, and image features, the SVM model obtained the best performance with AUC of 0.77 and 0.81 for predicting early sticky saliva and xerostomia, respectively. Also, SVM and MLP classifiers achieved a noteworthy AUC of 0.85 and 0.64 for predicting late sticky saliva and xerostomia, respectively.Conclusion. This study highlights the potential of baseline CT and MRI image features, combined with dosimetric data and patient demographics, to predict radiation-induced xerostomia and sticky saliva. The use of ML techniques provides valuable insights for personalized treatment planning to mitigate toxicity effects during radiation therapy for HNC patients.

Detection of Ochratoxin A in Tissues of Wild Boars (Sus scrofa) from Southern Italy

Ochratoxin A (OTA) is a secondary metabolite produced by fungi of the genera Aspergillus and Penicillium, known to contaminate various food substrates. Its toxic effects include direct nephrotoxicity, as well as observed teratogenic, immunogenic, and carcinogenic effects. Climate change may contribute to increased humidity and temperature, favouring fungal growth and, consequently, OTA spreading. Recent increases in wild boar populations, along with their omnivorous nature and their varied diet, define them as environmental bioindicators for contaminants like mycotoxins. This study aimed to assess the concentrations of OTA in kidney, liver, and muscle tissue samples from 74 wild boars that were hunted in different areas of Avellino, Campania region, between 2021 and 2022. Tissue samples underwent extraction, purification, and analysis using high-performance liquid chromatography (HPLC) coupled with a fluorescence detector. Results revealed OTA presence in 35.1% of tested wild boars. The highest OTA concentration was observed in the kidney and liver, with less in the muscle, indicating the presence of this mycotoxin in the wild boars and their surrounding environment. Consequently, there is a need to formulate rules for edible wildlife products. These findings emphasize the significant risk of OTA contamination in wild boar tissues, suggesting their potential as reliable environmental markers for mycotoxin prevalence and as a toxicological concern for human health.

Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial.

Advanced clear cell gynecological cancers (CCGCs) have a poor prognosis, with response rates to second-line chemotherapy less than 8%. Preliminary clinical activity with programmed cell death 1 protein (PD-1) inhibitors reported in CCGC merits further investigation. To assess the clinical benefit of pembrolizumab in patients with previously treated advanced CCGC. The PEACOCC trial is a single-arm multicenter phase 2 trial conducted at 5 UK centers investigating the clinical benefit and safety of pembrolizumab. PD-1 inhibitor-naive patients with histologically confirmed advanced CCGC, radiological disease progression following 1 or more prior courses of chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1 were included. Patients were enrolled from March 2019 to October 2021, with data collected until July 2024. Pembrolizumab, 200 mg, intravenously every 21 days up to 2 years until progression, discontinuation due to toxic effects, or patient/clinician decision. Up to 1 year of retreatment on diseases progression, if stable disease, partial response, or complete response at 2 years. The primary end point was progression-free survival (PFS) rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 to detect a 12-week PFS rate of 33% or greater and exclude a PFS rate of less than 15%, with 90% power and 1-sided 5% significance level. Secondary end points included objective response rate, duration of response, PFS, overall survival, safety, and quality of life. A total of 48 patients were eligible. The median (range) age was 58.5 (32-77) years, and 26 (54%) had an ECOG PS score of 0 and 22 (46%) had an ECOG PS score of 1; 41 (85%) had ovarian, 6 (13%) had endometrial, and 1 (2%) had cervical advanced CCGC. The median (range) courses prior therapy was 3 (1-6); 19 patients (40%) received prior anti-angiogenic therapy, and 19 (40%) had a platinum-free interval of more than 12 months. Grade 3 treatment-related adverse events were observed in 9 patients (19%), and no patients had grade 4 or 5 adverse events. A total of 45 of 46 patients (98%) had mismatch repair-proficient tumors. The 12-week PFS rate was 42% (95% CI, 28-57), and the best objective response rate was 25% (95% CI, 14-40), with 12 partial responses. After a median follow-up of 46.9 months (95% CI, 43.4-55.0), the median PFS was 2.7 months (95% CI, 1.3-5.4), and the median overall survival was 14.8 months (95% CI, 6.7-28.2). The PEACOCC trial showed clinical benefit with pembrolizumab in patients with previously treated advanced CCGC, of whom all except 1 had MMR-proficient disease. Clinical outcomes were durable with an overall tolerable safety profile, justifying further evaluation of pembrolizumab monotherapy for advanced CCGC in a randomized clinical trial. ClinicalTrials.gov Identifier: NCT03425565.

Risk Element Interaction with an Emerging Contaminant in Mammals: The Case of Arsenic and Carbamazepine Orally Taken up by Microtus arvalis L. as a Model Organism

Arsenic (As), a well-known ‘traditional’ environmental contaminant, and carbamazepine (CBZ), an emerging contaminant of a pharmaceutical category, are both frequently detected in the environment and have been shown to exhibit toxicity at exposure concentrations present in the environment. This study aimed to assess the single and combined exposure effects of these pollutants on the adult common vole (Microtus arvalis L.), a model mammalian organism. This study assessed As and CBZ accumulation, their biotransformation processes, and antioxidant enzyme defence responses after sole and combined exposure. The animals were fed a diet containing either a low (1.25 mg/kg) or high level (166 mg/kg) of As. Moreover, half of the animals were exposed to CBZ via drinking water infused with 10 ng/L of CBZ, and the second half had the use of drinking water devoid of CBZ. The results showed enhanced total As and As species contents in the organs of the As + CBZ exposure group compared to the As exposure group. High As exposure in the As + CBZ group did not cause an enhanced uptake of CBZ in the liver compared to the CBZ exposure group. There was a potential accumulation of CBZ in the liver of the CBZ exposed groups (CBZ and As + CBZ), raising concerns about potential toxic effects in mammals from long-term exposure. Glutathione peroxidase (GPx) activity, reflecting the antioxidant enzyme defence responses against single and co-exposure of the two pollutants, showed that the CBZ group exhibited comparable activity to the control group, while the As group had down-regulation and the As + CBZ group had up-regulation. These findings suggest that the CBZ group experienced minimal oxidative stress conditions, similar to the control group. The As group showed a rapid adaptation response to curtail or offset potential oxidative stress tissue damage conditions, compared to the slow adaptation/response in the As + CBZ group. The findings of this experiment indicate that the possible interactions of various environmental pollutants could alter the potential effects of the individual pollutants after a sole exposure. These findings indicate the necessity of investigating these interactions for better understanding of the potential risk of these pollutants in real environmental conditions.

Medical Toxicology Considerations for Space Exploration.

Spaceflight poses many risks to human health. Toxic exposures from inadvertent release of vehicle or payload chemicals and materials used in the operations of spaceflight are unique among them. There is a need for identification and development of clinical protocols for the management of toxic exposures before, during, and after spaceflight, particularly for acute exposures, because these events are likely to occur in austere environments with limited resources. The need for publicly available protocols is gaining importance as commercial spaceflight operations advance, and future spaceflight missions will require independence from Earth. This paper reviews the publicly available literature on toxic exposures in spaceflight to inform the development of relevant clinical practice guidelines. We performed a focused literature review and identified significant aerospace toxicologic incidents, including fatalities, injuries, and near-miss events. Sources included NASA-published literature, NASA safety reviews, published case reports, and published review articles. Searches were performed using the NASA Technical Reports Server, Google Scholar, and PubMed, and we included all cases involving exposure or potential exposure to an agent that could cause acute toxicity in spaceflight missions. Thirty-four cases were identified involving agents that can cause acute toxic effects. The two most common agents identified in acute toxicologic exposures in spaceflight operations were hydrazine and ammonia. These incidents can help us identify high-risk exposures so that we can develop protocols for the detection and management of future toxic exposures.

Aflatoxin B1-Induced Apoptosis in Donkey Kidney via EndoG-Mediated Endoplasmic Reticulum Stress

Aflatoxin B1 (AFB1) is a prevalent environmental and forage contaminant that poses significant health risks to both humans and livestock due to its toxic effects on various organs and systems. Among its toxicological effects, nephrotoxicity is a hallmark of AFB1 exposure. However, the precise mechanisms underlying AFB1-induced kidney damage in donkeys remain poorly understood. To investigate this, we established a donkey model exposed to AFB1 by administering a diet supplemented with 1 mg AFB1/kg for 30 days. Kidney apoptosis was assessed using TUNEL staining, while gene expression and protein levels of Endonuclease G (EndoG), as well as genes related to endoplasmic reticulum (ER) stress and apoptosis, were quantified by RT-qPCR and Western blotting. Our findings indicate that AFB1 exposure resulted in significant kidney injury, apoptosis, and oxidative stress. Notably, AFB1 exposure upregulated the expression of EndoG and promoted its translocation to the ER, which subsequently induced ER stress and activated the mitochondrial apoptotic pathway. These results suggest that AFB1-induced kidney damage in donkeys is mediated through the oxidative stress and mitochondrial apoptosis pathways, primarily involving the EndoG-IRE1/ATF6-CHOP signaling axis.

Metabolomic-Based Assessment of Earthworm (Eisenia fetida) Exposure to Different Petroleum Fractions in Soils

Background/Objectives: Petroleum contamination in soil exerts toxic effects on earthworms (Eisenia fetida) through non-polar narcotic mechanisms. However, the specific toxicities of individual petroleum components remain insufficiently understood. Methods: This study investigates the effects of four petroleum components—saturated hydrocarbons, aromatic hydrocarbons, resins, and asphaltenes—on earthworms in artificially contaminated soil, utilizing a combination of biochemical biomarker analysis and metabolomics to uncover the underlying molecular mechanisms. Results: The results revealed that aromatic hydrocarbons are the most toxic fraction, with EC50 concentrations significantly lower than those of other petroleum fractions. All tested fractions triggered notable metabolic disturbances and immune responses in earthworms after 7 days of exposure, as evidenced by significant changes in metabolite abundance within critical pathways such as arginine synthesis, a-linolenic acid metabolism, and the pentose phosphate pathway. According to the KEGG pathway analysis, saturated hydrocarbon fractions induced marked changes in glycerophospholipid metabolism, and arginine and proline metabolism pathways, contributing to the stabilization of the protein structure and membrane integrity. Aromatic hydrocarbon fractions disrupted the arachidonic acid metabolic pathway, leading to increased myotube production and enhanced immune defense mechanisms. The TCA cycle and riboflavin metabolic pathway were significantly altered during exposure to the colloidal fraction, affecting energy production and cellular respiration. The asphaltene fraction significantly impacted glycolysis, accelerating energy cycling to meet stress-induced increases in energy demands. Conclusions: Aromatic hydrocarbons accounted for the highest level of toxicity among the four components in petroleum-contaminated soils. However, the contributions of other fractions to overall toxicity should not be ignored, as each fraction uniquely affects key metabolic pathways and biological functions. These findings emphasize the importance of monitoring metabolic perturbations caused by petroleum components in non-target organisms such as earthworms. They also reveal the specificity of the toxic metabolic effects of different petroleum components on earthworms.

Positively Charged Nanoplastics Destruct the Structure of the PCK1 Enzyme, Promote the Aerobic Gycolysis Pathway, and Induce Hepatic Tumor Risks.

The production and weathering processes of nanoparticles (NPs) introduce charged functional groups on their surface. Previous studies have found that the surface charge properties of NPs play a critical role in their toxic effects and the mechanisms are generally attributed to their different accumulations and transmembrane potentials. Currently, we still lack sufficient knowledge about effects, owing to the unique structures of these polymers. In this study, positively charged NPs (PS-NH2, 50 nm) at 0.05-0.5 μg mL-1 promoted the proliferation of hepatic tumors in oncogenic KrasG12V zebrafish larvae and they also increased the viability of human hepatocellular carcinoma cells, whereas negatively charged NPs (PS-COOH, 50 nm) did not. We present evidence indicating that the potential carcinogenicity of PS-NH2 is related to the special polymer-molecular interactions caused by its positive surface charge. The affinity of PS-COOH chains for peptides typically enhances enzyme stability and upregulates its expression. However, PS-NH2 strongly competes with hydrogen bonds of the first rate-limiting enzyme PCK1 in gluconeogenesis, thus downregulating the expression of PCK1 and promoting the aerobic glycolysis pathway, which most tumor cells prefer. This study indicates that positive-charge modified NPs in the environment may bring additional carcinogenic risks.

Green remediation of lead (pb) from Pb-toxic soil by combined use of silicon nanomaterials and leguminous Lens culinaris L. plants

Lead (Pb) toxicity is a major issue due to anthropogenic activities that is faced by farmers nowadays which inhibits plant growth and decreases crop yields. From contaminated soils, Pb absorbed by the plants and then ultimately enters into the food chain. Silicon (Si) can reduce Pb availability to plants and can be helpful in Pb immobilization in the soils. Moreover, Si in its nano-form, is expected to augment the beneficial attributes of applied Si. However, very little is known regarding the prospects of nano-Si application and leguminous lentil for alleviating the effects of Pb stress. To assess the effectiveness of bulk Si and nano-Si for reducing Pb toxicity and improving the yield of lentils, a pot study was conducted. Lentil variety Punjab Masoor 2020 was examined under normal and Pb toxic conditions as affected by applied Si and nano-Si. There were eight treatments comprised of different combinations of Si at 100 and 200 mg Si kg− 1 soil, and nano-Si at 125 mg kg− 1 soil, which were tested against Pb at 500 mg kg− 1 soil. A completely randomized design with factorial arrangements was applied along with three replications each. The result showed that Pb toxicity reduced the plant growth, yield, total chlorophyll contents, membrane stability index, relative water content, shoot fresh weight and dry weights of lentil. Whereas Si and nano-Si lessened the negative effect of Pb toxicity by significantly reducing its concentration in plant roots and shoot, and improved agro-physiological traits of lentil in normal and Pb-toxic soil conditions. In soil spiked with 500 mg kg− 1 Pb, the application of 100 and 200 mg bulk Si per kg of soil and 125 mg kg− 1 nano-Si reduced the Pb concentration in shoot by 31, 62 and 84% respectively over controls. In squat, the application of nano-Si most significantly (p ≤ 0.05) reduced the root and shoot Pb concentration in lentil.

Dose-Dependent PFESA-BP2 Exposure Increases Risk of Liver Toxicity and Hepatocellular Carcinoma

Per- and polyfluoroalkyl substances (PFASs) are persistent and highly bioaccumulative emerging environmental contaminants of concern that display significant toxic and carcinogenic effects. An emerging PFAS is PFESA-BP2, a polyfluoroalkyl ether sulfonic acid found in drinking water and the serum of humans and animals. While PFESA-BP2-induced liver and intestinal toxicity has been demonstrated, the toxicological mechanisms and carcinogenic potential of PFESA-BP2 have remained relatively understudied. Here, we studied how different doses of PFESA-BP2 affect gene activity related to liver toxicity and the risk of liver cancer such as hepatocellular carcinoma (HCC) in mice exposed to PFESA-BP2 once daily through oral gavage for seven days. An analysis of key hepatic pathways suggested increased risk of hepatotoxicity as a result of PFESA-BP2 exposure. Increased oxidative stress response was associated with all concentrations of exposure. Liver toxicity pathways, including PXR/RXR activation and hepatic fibrosis, showed dose-dependent alteration with activation primarily at low doses, suggesting an increased risk of hepatic inflammation and injury. Additionally, an analysis of carcinogenic and HCC-specific pathways suggested PFESA-BP2-induced risk of liver cancer, particularly at low doses. Low-dose PFESA-BP2 exposure (0.03 and 0.3 mg/kg-day) was associated with an increased risk of HCC carcinogenesis, as indicated by the activation of tumor-related and HCC-associated pathways. In contrast, these pathways were inhibited at high doses (3.0 and 6.0 mg/kg-day), accompanied by the activation of HCC-suppressive pathways. The increased risk of HCC development at low doses was mechanistically linked to the activation of signaling pathways such as HIF, EGF, NOTCH4, HGF, and VEGF. Biomarkers linked to liver cancer risk, prognoses, and diagnoses were also identified as a result of exposure. Overall, our findings on liver carcinogenic and hepatotoxic pathway activation patterns suggest that PFESA-BP2 increases the risk of liver toxicity and HCC development, particularly at low doses.

TMEM45A enhances palbociclib resistance and cellular glycolysis by activating AKT/mTOR signaling pathway in HR+ breast cancer

Palbociclib, a CDK4/6 inhibitor, plays a crucial role in the treatment of HR+ breast cancer. However, resistance to palbociclib is a significant concern that merits further investigation. Our investigation identifies TMEM45A as a potential driver of palbociclib resistance and its association with increased cellular glycolysis. We demonstrate that TMEM45A is highly expressed in palbociclib-resistant breast cancer (BRCA) cells, correlating with enhanced tumor progression. Silencing TMEM45A enhances sensitivity to palbociclib, promotes cell cycle arrest and apoptosis, and inhibits the proliferation of BRCA cells. Moreover, attenuation of TMEM45A expression reduces cancer aggressiveness by decreasing the expression of EMT and glycolysis-related proteins. Subsequent gene set enrichment analysis (GSEA) confirms that TMEM45A activates the AKT/mTOR signaling pathway, which is integral to cell cycle progression and glycolysis. In a cell line-derived xenograft (CDX) mouse model, TMEM45A knockdown significantly restores sensitivity to palbociclib and suppresses tumor growth. Additionally, the use of engineered exosomes loaded with siRNA targeting TMEM45A presents a promising strategy for enhancing CDK4/6 inhibitor sensitivity without observable toxic side effects in a patient-derived xenograft (PDX) model. Collectively, our findings suggest that TMEM45A may be a therapeutic target for overcoming palbociclib resistance, and exosomal siRNA delivery could be a viable strategy for precision medicine in HR+ breast cancer.

Spatiotemporal 3D cell impedance monitoring for metal nanoparticle risk assessment by plug-in vertical electrode array.

Metal nanoparticles are commonly found in our daily lives and pose great risks to people's health. Therefore, it is crucial to establish a research model for the toxic effects of metal nanoparticles. In recent decades, three-dimensional (3D) cell models have attracted increasing interest in the fields of cell barriers, nanotoxicology, and drug screening, as they have significant advantages over two-dimensional (2D) cell models in accurately simulating in vivo behavior of human cells. The accurate spatiotemporal reaction characteristics achieved through the diffusion effect of metal nanoparticles in Matrigel scaffolds are of great importance in nanotoxicology. However, traditional impedance sensors face challenges in performing spatiotemporal dynamic impedance monitoring and evaluating the toxic impact of metal nanoparticles on 3D cells. Here, we propose an impedance sensor that integrates a plug-in vertical electrode array (PVEA) chip with a multi-channel detection system. This sensor can dynamically record 3D cell impedance in the vertical direction, which is consistent with the temporal and spatial progression of metal nanoparticle penetration, and also closely related to the spatiotemporal activity of cells influenced by metal nanoparticles. This method can detect subtle changes in impedance signals at different positions caused by the diffusion of metal nanoparticles, and has high application value in Nanotoxicology evaluation. This universal, high-throughput 3D cell impedance sensor has great potential in toxicity detection and drug screening.

Acute and Chronic Cardiovascular Adverse Events in Patients with Acute Myeloid Leukemia: A Systematic Review

Background/Objectives: Patients with acute myeloid leukemia (AML) have a higher propensity for adverse cardiovascular outcomes, primarily due to the toxic effects of chemotherapeutic agents. The purpose of this systematic review is to explore the association of acute myeloid leukemia treatment with adverse cardiovascular events. Methods: We systematically screened the literature for studies providing comparative data on cardiovascular toxicities in patients treated for acute myeloid leukemia. After the initial search, 3649 papers were screened and a final total number of 46 were included for the review process. Results: Common chemotherapeutic agents used in AML may cause cardiovascular (CV) toxicities. A plethora of pathophysiological mechanisms are incriminated for these effects. Drug combinations may increase the risk in a synergistic way. In addition, common mutations of AML, personal history of previous cardiovascular disease and impaired heart function carry an increased complication risk. Biomarkers, as well as multimodality imaging, may be used for the early detection of cardiovascular toxicities. Conclusions: Increased risks of CV toxicity and comorbidities are observed among AML patients. With all the available diagnostic modalities, early detection and CV prevention strategies can improve the patient’s prognosis and quality of life.

Development and characterization of a cell line from the caudal fin of Schizothorax niger (Heckel, 1838) for in vitro toxicity testing.

Here, we successfully grew the SNCF (Schizothorax niger caudal fin) cell line from the caudal fin explants of S. niger, an important cold-water fish of the Himalayas. The cells were successfully grown up to 22 passages by planting explant tissues in DMEM medium supplemented with FBS. We observed optimal cell growth at a concentration of 18% FBS. We observed the steady generation of cells from explants from days 2 to 5 of seeding, and obtained a complete monolayer at days 7-10. We tested various temperatures, including 10°C, 13°C, 16°C, 19°C, 22°C, 25°C, and 28°C, and found that 22°C was the optimal temperature for cell growth. We examined the response to various doses of epidermal growth factor (EGF) and fibroblast growth factor (FGF) (0, 2, 4, 6, 8, and 10ng/mL) on cell colony growth at an optimal temperature of 22°C. We characterized the cell line using karyotyping at the 14th and 20th passages. The cell line showed epithelial cell-like growth by morphology, which was confirmed by immunotyping. We further used the cell line to study the impact of three pesticides (chlorpyrifos, dimethoate,and endosulfan), and a fungicide (mancozeb) and bacterial extracellular product (ECP). The DAPI stain assay and MTT assay confirmed the pesticides toxic effects on the cells, revealing disintegration of the cell nuclei by the formation of micronuclei and LC50 concentrations. ECP treatment showed disruption of the monolayer within 0-36hrs.

The Acute Toxicity and Cardiotoxic Effects of Levofloxacin on Zebrafish (Danio rerio)

Emerging contaminants refer to chemical substances that have not been widely regulated but possess the potential to cause adverse effects on both the environment and human health. Antibiotics, as emerging contaminants, pose significant threats to ecosystems and human health due to their widespread use and persistence in the environment. Levofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly employed in the treatment of bacterial infections, and has been frequently detected in environmental matrices and freshwater systems. In this study, we assessed the effects of levofloxacin on hatchability, mortality rates, malformations, behavioral changes, and cardiac development in zebrafish embryos by exposing them to varying concentrations of levofloxacin (0, 0.5, 1, 2, 4, and 8 mM). Our results demonstrate that levofloxacin exposure significantly impaired the growth and development of zebrafish larvae, particularly at higher concentrations. Notable effects included reduced body length, abnormal yolk sac and swim bladder development, pericardial edema, prolonged distances between the sinus venosus and arteriolar bulb (SV-BA), and disruptions in heart rate. Quantitative PCR analysis further revealed that levofloxacin exposure significantly upregulated the expression of key cardiac development genes in zebrafish larvae, including nppa, myh6, cacna1ab, myl7, gata4, nkx2.5, tbx2b, and tbx5b. These findings indicate that levofloxacin exposure exerts significant toxic effects on both embryonic and larval growth as well as heart development and gene expression in zebrafish. This study provides critical insights into the potential ecological risks posed by levofloxacin along with other antibiotics while laying a foundation for further investigation into their toxicological mechanisms.

Hydrophobic Chitosan Derivatives for Gene and Drug Delivery in Cancer Therapies

Chitosan remains one of the most widely used biopolymers in biomedicine due to its non-toxicity and biodegradability. It is easily chemically modified, allowing its properties to be effectively altered to improve its performance as a gene and drug carrier. The introduction of hydrophobic moieties into chitosan can significantly enhance its interaction with cancer cells, improving its potential for targeted delivery. The hydrophobic moiety plays a crucial role in the interaction of the particle with the cell membrane during internalization by endocytosis. The type of hydrophobic moiety, its degree of substitution, and its placement along the chitosan backbone all influence the physicochemical properties and biological performance of the resulting polymer. Hydrophobic modification can also affect the self-assembly behavior of chitosan, influencing the size, shape, and stability of the resulting particles. These factors impact the loading efficiency of therapeutic agents and the release kinetics of the encapsulated cargo. While hydrophobic modification can enhance the therapeutic efficacy of chitosan, it is important to consider potential toxic effects. In summary, the hydrophobic modification of chitosan is a powerful strategy to improve its efficiency as a gene and drug carrier. By understanding the role of the hydrophobic moiety in cellular uptake, endosomal escape, self-assembly, and toxicity, researchers can design and develop optimized chitosan-based delivery systems for targeted cancer therapy.

Effect of Cd–Zn compound contamination on the physiological response of broad bean and aphids

IntroductionThe heavy metal elements cadmium (Cd) and zinc (Zn) often coexist in nature, making the environmental media more prone to compound pollution. However, research on the toxic effect of the Cd–Zn combination is still lacking, and the underlying toxic mechanisms remain unclear.MethodsTherefore, in this experiment, we established four treatment groups with different ratios of Cd–Zn compound stress for the broad bean, Vicia faba L., and aphids, Megoura crassicauda, to explore the growth and physiological adaptation mechanisms under different levels of mixed heavy metal stress.ResultsBy measuring the germination rate, seedling height, and chlorophyll content of broad beans, we found that Cd–Zn-mixed stress has a synergistic inhibitory effect on the growth and development of broad beans. Cd and Zn can be transferred through the food chain, while broad beans can resist complex stress by regulating the content of total soluble sugars and photosynthetic pigments in the body, as well as accumulating proline. In addition, in the first generation of adult aphids, treatment with Cd (12.5 mg/kg) + Zn (100 mg/kg) significantly affected the expression of trehalase (TRE) and trehalose-6-phosphate synthase (TPS) genes and influenced the carbohydrate content and trehalase activity in the aphids.DiscussionThe number of offspring produced by the second-generation aphids was significantly reduced under mixed heavy metal treatment, but it was not caused by changes in the vitellogenin (Vg) content. These related results provide new avenues for further exploration of plant responses to mixed heavy metal stress, pest control, and management of heavy metal pollution.

Impact of cigarette smoking on genetic stability, cell division and cytotoxicity in buccal cells of old and young woman.

We investigated the impact of cigarette smoking, daily exposure to tar and nicotine, and the duration of smoking on genetic instability (chromosomal damage - micronuclei, MN, nuclear buds - gene amplification) as well as on disturbances in mitosis (resulting in binucleated cells). Furthermore, we analyzed markers of cytotoxic effects (such as the formation of condensed chromatin, pyknotic, karyolytic, and karyorrhectic cells) and the mitotic activity of the oral mucosa. These parameters were monitored in groups of old (postmenopausal) and young (premenopausal) smoking and non-smoking women (n= 25/group). We found no differences of the MN frequencies in the non-smoking groups and only a moderate (not significant) increase of MN in both groups of smokers. However, we observed a clear increase of markers of genomic instability in both smoking groups. Furthermore, the mitotic activity of cells in the mucosa and of anomalies caused by acute cytotoxicty was higher in both smoking groups. Nicotine uptake was associated with pronounced acute toxic effects and increased the cell division rate. Chromosomal damage (MN) was higher in individuals which consumed high amounts of tar (this effect was not significant) and caused moderate acute toxicity. Our findings indicate (i) that age and hormonal status have no strong impact on the genotoxic and cytotoxic effects in smoking women, (ii) consumption of up to 30 cigarettes/day does not cause chromosomal damage in buccal cells, however positive results were found in earlier studies in heavy smokers, (iii) smoking increased markers which reflect genetic instability and the division rate of oral mucosa cells. These effects may play a role in neoplastic transformation of cells in the upper respiratory tract in smokers. The duration of smoking was associated with a slight (not significant) increase of the mitotic activity and of chromosomal damage and with moderate acute cytotoxicity.

Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Currently, it has shown a trend of earlier onset, with most patients experiencing a progressive decline in cognitive function following the disease's onset, which places a heavy burden on society and family. Since no drug cure for AD exists, exploring new ways for its treatment and prevention has become critical. Early vascular damage is an initial trigger for neuronal injury in AD, underscoring the importance of vascular health in the early stages of the disease. Patients with early AD experience abnormal blood-brain barrier transport of amyloid-β (Aβ) peptides, with excess Aβ being deposited in the cerebral vasculature. The toxic effects of Aβ lead to abnormalities in cerebrovascular structure and function. Fibroblast growth factor21 (FGF21) is an endocrine factor that positively regulates energy homeostasis and glucose-lipid metabolism. Notably, it is one of the effective targets for metabolic disease prevention and treatment. Recent studies have found that FGF21 has anti-aging and vasoprotective effects, with receptors for FGF21 present in the brain. Exercise stimulates the liver to produce large amounts of FGF21, which enters the blood-brain barrier with the blood to exert neurovascular protection. Therefore, we review the biological properties of FGF21, its role in the cerebrovascular structure and function in AD, and the mechanism of exercise-regulated FGF21 action on AD-related cerebrovascular changes, aiming to provide a new theoretical basis for using exercise to ameliorate degenerative neurological diseases.

Effect of Bacteria from the Genus Azospirillum on Oxidative Stress Levels in Wheat Triticum aestivum L. in the Presence of Copper, Nickel, and Lead

Heavy metals (HMs) exert a negative impact on physiological processes in plants, which can adversely affect the productivity of agricultural crops. In this experiment, we assessed the potential to mitigate the toxic effects of HMs on soft wheat through the use of rhizospheric microorganisms from the genus Azospirillum. In the initial phase of the experiment, we identified the most resistant Azospirillum strains to Cu (from 1.5 to 15 mg/L), Ni (from 2 to 20 mg/L), and Pb (from 15.9 to 159.4 mg/L). Both Ni and Pb significantly inhibited bacterial growth and induced substantial oxidative stress in the majority of the studied strains. The strain A. picis B-2897T exhibited the highest resistance to all HMs. The cultivation of wheat in soil supplemented with Cu led to an increased growth rate and enhanced wheat productivity. Conversely, Ni and Pb reduced wheat productivity by 65% and 27%, respectively. This was accompanied by chlorophyll depletion and a decrease in the expression of genes NDOR and GST, which are involved in xenobiotic detoxification. Pre-inoculation of seeds with Azospirillum led to a decrease in HM concentration in the plant seedlings; in particular, A. picis B-2897T reduced the level of Ni from 0.005% to a concentration below the detectable level (i.e., below 0.001%), and Pb from 0.014% to 0.008%. The bacteria stimulated the expression of genes responsible for xenobiotic detoxification and contributed to the increased growth and productivity of wheat. Thus, Azospirillum can be utilized as a bioproduct to alleviate the toxic effects of HMs.