Search Results (320)

The taxane family of compounds, including paclitaxel, docetaxel (Taxotere), and cabazitaxel (Jevtana), are common drugs used in chemotherapy for the frontline treatment of most major types of cancer. Alopecia, the dramatic loss of hair, is a common side effect that became a symbol of the suffering of many cancer patients. Concerted efforts have been made to understand the mechanism of taxane toxicity to hair follicles and, thus, prevention methods. Taxanes act by stabilizing cellular microtubules, which consequently cause mitotic arrest and then failure, as microtubules play critical functions in chromosome segregation. Hair follicle matrix cells are highly proliferative and thus are exceedingly sensitive to taxanes. We review the cellular mechanism-based strategies under investigation to counter taxane-induced hair follicle damage. These include the application of cyclin kinase inhibitors to block mitotic entry, the practical method using scalp cooling to reduce exposure of scalp hair follicles to drugs during infusion, the requirement of p53 action for hair follicle damage, and the recently discovered method of using low-intensity ultrasound to break taxane-stabilized microtubules and thus reverse taxane toxicity in hair follicle matrix cells. The concept of low-intensity ultrasound as an antidote to taxanes may have the potential to provide a practical and compelling strategy to counter alopecia in cancer treatment using taxanes. Tweet: Taxanes (paclitaxel/docetaxel) are powerful microtubule-stabilizing cancer drugs, but they also cause adverse effects, including alopecia. New research discoveries of temporary microtubule disruption by low-intensity ultrasound may counteract taxane toxicity and prevent alopecia during cancer chemotherapy. “Mechanistic-based strategies for the prevention of taxane-induced hair follicle damage in cancer chemotherapy” OUTLINE: 1. Taxane/paclitaxel mechanism of action in cancer therapy. 2. Taxane side effects: Alopecia (hair loss). 3. p53 dependence of taxane-induced hair follicle damage. 4. Research efforts to counter taxane -induced alopecia by CDK4/6i. 5. Prevention of taxane chemotherapy side effects using scalp cooling. 6. Discovery of low-intensity ultrasound as an antidote for taxane cytotoxicity, and potential prevention of alopecia in chemotherapy using taxanes. 7. Summary and prospective. Full article

Deaths from the accidental ingestion of poisonous Amanita mushrooms occur every year due to the lack of a specific antidote against α-amanitin poisoning. Intervention and treatment can be promptly carried out to avoid serious consequences when the toxin can be effectively detected in whole blood before liver toxicity develops. Aptamers are molecular recognition units similar to antibodies, capable of specifically recognizing and detecting small molecules such as α-amanitin for which monoclonal antibodies are difficult to prepare. However, α-amanitin has a small molecular size and limited binding sites, which bring difficulties to aptamer selection. Moreover, achieving highly specific detection of α-amanitin in whole blood remains challenging due to the presence of potentially interfering components, such as human serum albumin (HSA). For these problems, we propose an aptamer selection method for small-molecule target α-amanitin, combining target-immobilized and library-immobilized SELEX to select high-affinity aptamers. To exclude HSA interference, counter-selection was introduced to remove HSA-bound sequences. Through these strategies, we successfully selected a highly specific α-amanitin aptamer with nanomolar affinity. Full article

Intensive recirculating aquaculture systems are vulnerable to spikes of nitrite, which oxidizes hemoglobin to methemoglobin and compromises oxygen transport. Methylene blue (MB) is a classical antidote for methemoglobinemia, yet its use in fish has been limited to injections or immersion baths that are impractical for large-scale operations. This study assessed whether MB incorporated into a medicated feed could mitigate acute nitrite intoxication in Nile tilapia. Fish received either a control diet or 0.1% MB diet. After five days on the experimental diets, fish were exposed to nitrite for 48 h. Control fish experienced five deaths, whereas no mortality or behavioral distress was observed in MB-treated fish. Hematology indicated significantly lower circulating methemoglobin concentration in the MB group, while the control fish had higher hemoglobin concentration and erythrocyte counts, consistent with compensatory erythropoiesis. Gill histology revealed preserved lamellae with only mild changes in MB-fed fish, whereas control fish displayed lamellar aneurysm, edema, capillary congestion, fusion and epithelial hyperplasia. Therefore, oral MB administration appears to ameliorate the physiological consequences of acute nitrite exposure, offering a scalable intervention for emergency management of nitrite spikes. Future work should define dose–response relationships, evaluate post-exposure rescue, quantify gill lesions and assess MB residues in food fish. Full article

Background: Direct oral anticoagulants (DOACs) have transformed antithrombotic therapy but carry significant bleeding risks requiring prompt reversal. Recent regulatory changes have altered the reversal landscape, notably with the withdrawal of andexanet alfa from the U.S. market. Anticoagulation stewardship programs (ASPs) are essential for navigating this evolving environment and optimizing safe use of anticoagulants. Methods: This narrative review synthesizes evidence from landmark clinical trials (RE-VERSE AD, ANNEXA-4, ANNEXA-I), contemporary guidelines, emerging literature on reversal agents, and critical regulatory updates including the 2025 U.S Food and Drug Administration (FDA) withdrawal of andexanet alfa. Results: Idarucizumab remains the only FDA-approved specific antidote for dabigatran. Following the withdrawal of andexanet alfa, prothrombin complex concentrates (PCCs), both 4-factor and activated are now the primary reversal options for Factor Xa inhibitors, with recent evidence demonstrating comparable hemostatic efficacy. Ciraparantag, a universal reversal agent, is currently in Phase III development. Effective ASPs must now adapt protocols to the post-andexanet era while ensuring timely access to alternative reversal strategies. Conclusions: The reversal landscape has undergone a fundamental transformation with the loss of andexanet alfa. Success in DOAC-associated bleeding management now depends on optimizing PCC-based strategies, integrating systematic stewardship approaches, and preparing for emerging universal antidotes. Institutions must urgently update algorithms, ensure PCC availability, and monitor outcomes in this new therapeutic environment. Full article

Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by phosphylating the catalytic serine. Oxime reactivators can restore enzymatic activity by a nucleophilic attack of the oximate anion on the phosphorus center of the enzyme–OP conjugate; however, clinically used oximes show agent- and enzyme-dependent performance and are particularly challenged by A-series compounds. Here, an in silico strategy is presented to identify candidate antidotes for OP poisoning, including A-series agents. Pharmacophore models are generated from benchmark/template oximes. Pharmacophore-based virtual screening is used to retrieve hit-like scaffolds from the available chemical space, after which selected hits are converted into oxime analogs. Template oximes and newly designed oximes are then docked into the active site of AChE or BChE inhibited by specific nerve agents. The predicted reactivation potential is assessed using mechanistically motivated geometric criteria derived from the accepted reactivation hypothesis, including the distance between the oximate oxygen and the phosphyl phosphorus and the attack angle, relative to the catalytic serine Oγ. This workflow enables a controlled, pairwise comparison of new oximes against their corresponding template oximes for each enzyme–agent combination, providing a rational basis for prioritizing candidates for synthesis and experimental validation. Using the described workflow, we identified a hit compound with the potential to act as an antidote against A-series nerve agent A-230 poisoning. Full article

Aptamers, short single-stranded DNA or RNA oligonucleotides, are emerging as transformative tools in cardiology for the diagnosis, treatment, and theranostics of cardiovascular diseases (CVDs). This review highlights their dual utility. In diagnostics, aptamers enable the construction of highly sensitive biosensors for key cardiac biomarkers (e.g., troponins, myoglobin, C-reactive protein, natriuretic peptides), outperforming conventional assays and enabling early detection and point-of-care testing. Therapeutically, aptamers offer targeted, controllable, and reversible anticoagulation, as demonstrated by clinical-stage candidates like BT200 (anti-vWF) and NU172 (anti-thrombin), whose action can be rapidly reversed with antidote oligonucleotides. Furthermore, aptamers serve as precision delivery vehicles (e.g., Gint4.T, RNA-Apt30) for transporting therapeutic peptides or nucleic acids specifically to cardiomyocytes. Recent integration with nanomaterials (quantum dots, graphene, liposomes, DNA origami) has led to advanced biosensing and drug delivery platforms. Despite challenges like stability and the polyethylene glycol (PEG) immunogenicity, ongoing clinical trials underscore the significant potential of aptamer technology to bridge precise diagnostics and targeted therapy, paving the way for innovative, personalized CVD interventions.) Full article

The publication of Richard Wilhelm’s German translation of the Daodejing in 1911 ignited a “Daoist enthusiasm” in German literary circles, offering spiritual solace to a generation disillusioned by World War I. This article explores the creative reception of Daoist thought by the German writer Klabund (1890–1928), arguing that he reinterpreted Daoism not merely as a philosophy but as a religious response to the spiritual and political crises of post-war Germany. Through a comparative analysis of Klabund’s Laotse. Sprüche and Wilhelm’s source text, this study reveals how Klabund, through the selection, reorganization, and substitution of key terms, constructs a “practicable faith” for his contemporaries. The article further examines how this reconstruction extends into his literary works: Li-Tai-Pe aestheticizes Daoist themes like “softness” and “water”, Dreiklang elevates Laozi to a “divine incarnation” within a syncretic religious framework alongside Christ and Buddha, and The Last Emperor applies Daoist political wisdom to critique imperial power. Klabund’s approach illustrates a unique model of cross-cultural dialogue, where ancient Eastern wisdom is transformed into a “revolution of the heart”, serving as a spiritual antidote to the modern Western crisis of faith. Full article

Heparin (Hep) and its clinical antidote protamine (PRO) play essential yet antagonistic roles in anticoagulant therapy, necessitating reliable analytical tools to monitor their levels and interactions. Herein, we report that coptisine chloride (COP), a natural isoquinoline alkaloid, acts as an aggregation-induced emission (AIE) sensor enabling dual-responsive fluorescence modulation toward Hep and PRO. Owing to its rigid polycyclic and intrinsically twisted molecular framework, COP displays typical AIE behavior. In a DMSO/PBS mixture (PBS fraction = 99%, v/v), COP forms strongly emissive aggregates with Hep through electrostatically driven complexation, allowing sensitive Hep detection with a limit of detection (LOD) of 0.70 μg/mL. Subsequent competitive binding of PRO to Hep disrupts the COP–Hep aggregates, giving rise to fluorescence quenching and reversible PRO sensing (LOD: 0.49 μg/mL). Theoretical calculations together with multiple characterization techniques reveal an aggregation–disaggregation mechanism governing the dual fluorescence modulation. Moreover, COP achieves accurate Hep quantification in spiked diluted human serum, affording satisfactory linearity and recoveries (LOD = 0.71 μg/mL; recoveries 98.3–101.6%). These results demonstrate that COP, a structurally simple natural AIE luminogen, serves as a sustainable, biocompatible, and accessible tool for reversible Hep and PRO analysis in complex media. Full article

Despite growing concerns about the ecological and health risks of nanoplastics at environmentally relevant concentrations (ERCs), the effects of polyurethane nanoplastics (PU NPs) on environmental organisms remain unclear. This study assessed the toxicity of PU NPs in the μg/L range in Caenorhabditis elegans (C. elegans) through chronic exposure. Our results showed that 10 μg/L PU NP exposure significantly reduced brood size, head thrashes, and body bends, while 100 μg/L PU NP exposure decreased lifespan, and 1000 μg/L PU NP exposure increased mortality in wild-type C. elegans. Analysis of oxidative stress showed that both 10 and 1000 μg/L PU NP exposures elevated reactive oxygen species (ROS), SKN-1::GFP, and GST-4::GFP levels. Notably, while ROS production rose at 1000 μg/L, SKN-1::GFP and GST-4::GFP expression decreased compared to the 10 μg/L group, suggesting a compensatory response in C. elegans at lower exposure levels. The expression of oxidative stress-related genes and phenotype of differentially expressed genes indicated that C. elegans was in a compensatory phase when exposed to 10 μg/L of PU NPs, participating in the protective response of C. elegans to PU NPs. However, when exposed to 1000 μg/L of PU NPs, C. elegans was in a decompensatory phase, participating in the toxic regulation of PU NPs. In addition, under 10 μg/L PU NP exposure, cinnamon essential oil (CIEO) can enhance the expression of more antioxidant enzymes, thereby increasing the protective effect. Under 1000 μg/L PU NP exposure, CIEO could alleviate the toxic response of C. elegans to PU NPs exposure by promoting the expression of skn-1. Molecular docking analysis showed that the main active component of CIEO, cinnamaldehyde (CID), has a strong affinity with SKN-1/Nrf2. Our study is the first to emphasize the toxic effects of PU NPs on environmental organisms at ERCs and that CIEO might serve as a potential antidote for nanoplastic poisoning. Full article

Aflatoxin B₁ (AFB₁), a major metabolite of aflatoxin, is a highly toxic carcinogen. It frequently contaminates feed due to improper storage of feed ingredients such as corn and peanut meal, with the contamination risk further escalating alongside the increasing incorporation of plant-based proteins in feed formulations. Upon entering an organism, AFB₁ is metabolized into highly reactive derivatives, which trigger an oxidative stress-inflammation vicious cycle by binding to biological macromolecules, damaging cellular structures, activating apoptotic and inflammatory pathways, and inhibiting antioxidant systems. This cascade leads to stunted growth, impaired immunity, and multisystem dysfunction in animals. Long-term accumulation can also compromise reproductive function, induce carcinogenesis, and pose risks to human health through residues in the food chain. Tannins are natural polyphenolic compounds widely distributed in plants which exhibit significant antioxidant and anti-inflammatory activities and can effectively mitigate the toxicity of AFB₁. They can repair intestinal damage by increasing the activity of antioxidant enzymes and up-regulating the gene expression of intestinal tight junction proteins, regulate the balance of intestinal flora, and improve intestinal structure. Meanwhile, tannins can activate antioxidant signaling pathways, up-regulate the gene expression of antioxidant enzymes to enhance antioxidant capacity, exert anti-inflammatory effects by regulating inflammation-related signaling pathways, further reduce DNA damage, and decrease cell apoptosis and pyroptosis through such means as down-regulating the expression of pro-apoptotic genes. This review summarizes the main harm of AFB₁ to animals and the mitigating mechanisms of tannins, aiming to provide references for the resource development of tannins and healthy animal farming. Full article

This study explores the spread of malware within a digital framework by introducing a unique fractional-order model that employs the Atangana–Baleanu–Caputo (ABC) derivative. As cyber threats grow increasingly sophisticated and widespread, traditional models using classical differential equations often prove inadequate, particularly in capturing long-term memory effects and historical dependencies inherent in real-world systems. To address these challenges, the proposed approach utilizes the non-local characteristics of fractional calculus, offering a more comprehensive framework for understanding malware behavior. The model includes the derivation of the basic reproduction number, ${\Re }_0$, to evaluate conditions for malware persistence or elimination, sensitivity analysis and examines equilibrium states to assess overall system stability. Theoretical analysis ensures the existence and uniqueness of solutions through fixed-point techniques. Through numerical simulations, the theoretical results are validated, emphasizing the significant impact of antidotal and recovery measures in controlling malware spread. These findings provide essential guidance for enhancing the protection and robustness of sophisticated cyber-physical and humanoid infrastructures. Full article

Organophosphate (OP) insecticide poisoning remains a significant world health issue. Despite attempts to reduce OP insecticide use in some countries, they continue to be used extensively in many regions, putting agricultural workers at risk of excess exposure. Furthermore, the high toxicity and ready availability of OP insecticides in agricultural settings have created an additional public health issue due to their use in attempted suicides. Tens of thousands of people are admitted to hospitals every year after intentional ingestion of OP insecticides. The standard treatment regimen for OP poisoning can prevent mortality, even in some severe cases, but these treatments do not protect the central nervous system (CNS) from excitotoxic damage, and therefore, additional neuroprotective treatments are needed. One promising treatment is the use of halogenated ether anesthetics, including isoflurane, a common anesthetic available in hospitals throughout the world. Isoflurane can be administered by inhalation using vaporizer equipment, or it can be injected intravenously as a lipid–water emulsion. In both cases, excellent neuroprotection has been observed in preclinical models, even when administered up to 1 h after the onset of OP insecticide poisoning. Prolonged administration was not necessary for neuroprotective efficacy, with administration times of only 5 min being sufficient. Including inhalational anesthetics as an adjunct to the standard treatment for OP poisoning could significantly reduce chronic morbidities, especially long-term CNS damage. Research is ongoing to bring this promising treatment to human trials. Full article

This work aimed to synthesize new derivatives of 2-hydrazinylpyridine-3-carbonitrile and to investigate their biological activity as safeners for the 2,4-D herbicide. The new 2-hydrazinylnicotinonitriles were obtained in high yields (up to quantitative) under mild conditions (25 °C, dioxane) by treating 4,6-diaryl-2-bromo-3-cyanopyridines with hydrazine hydrate. The latter were synthesized by brominating 2-(3-oxo-1,3-diarylpropyl)malononitriles, the Michael adducts, which are readily available from 1,3-diarylpropenones (chalcones) and malononitrile. An unusual side product of the bromination/carbocyclization was isolated and characterized; it consisted of co-crystals of 3-benzoyl-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile and 3-benzoyl-5-bromo-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile at a ~4:6 ratio. The new 2-hydrazinylnicotinonitriles react with halogen-containing aromatic aldehydes to form the corresponding hydrazones. The biological activity of the new nicotinonitriles was examined for their function as 2,4-D antidotes. It was found that, under laboratory conditions, eight of the synthesized compounds exhibited a notable antidote effect against 2,4-D on sunflower seedlings. Full article

Ferroptosis is a novel iron-sensitive subtype of regulated cell death (RCD), persisting under extreme lipid peroxidation and iron/redox imbalances. Unlike apoptosis, necroptosis, and pyroptosis, ferroptosis is a signaling-driven process mediated through iron metabolism imbalance, polyunsaturated fatty acid (PUFA) exceeding oxidation, and defects in its protective systems like Xc-/GSH/GPx4. Specifically, this review establishes that iron-driven ferroptosis is a central underlying pathomechanistic factor in a broad range of human diseases. Significantly, whether its modulation is therapeutic, it is entirely conditional on the specific disease context. Thus, its induction can provide a promising antidote for destructive cancer cells when conjoined with immuno-therapies to boost anticancer immunity. Conversely, iron-mediated ferroptosis suppression is a key factor in countering destructive changes in a whole range of degenerative and acute injuries. Current therapeutic approaches include iron chelators, lipid oxidation inhibitors, GPx4 activators, natural and active compounds, and novel drug delivery systems. However, against all odds and despite its intense therapeutic promise, its translation into a practical medicinal strategy faces many difficulties. Thus, a therapeutic agent specifically focused on its modulation is still lacking. The availability of selective biologic markers is a concern. The challenges in the direct pathologic identification of ferroptosis in a complex in vivo systemic scenario remain. Current avenues for its future development are pathogen infections, the discovery of novel regulating factors, and novel approaches to personalized medicine centered on its organ-level in vivo signatures. Full article

Background/Objectives: This study aimed to comprehensively characterize the prevalence and patterns of drug-induced hospitalizations and death and to identify predictors strongly associated with drug-induced death. Methods: This study analyzed 29,438 serious adverse event (SAE) reports submitted to the Korea Adverse Event Reporting System (KIDS KAERS DB) database between January 2019 and December 2023. Disproportionality analysis was conducted to detect drug–event associations, and multiple logistic regression was performed to identify independent predictors of mortality. Results: Mortality accounted for 7.53% (n = 2217) and hospitalization for 93.53% (n = 27,532). The strong signals for drug-induced death were observed with steroids (ROR 3.81, 95% CI 3.39–4.27), antidotes (ROR 3.65, 95% CI 2.15–6.18), and anticoagulants (ROR 2.01, 95% CI 1.73–2.34). Immunosuppressants (ROR 9.17, 95% CI 4.75–17.70), diuretics (ROR 3.83, 95% CI 1.42–10.31), and antihyperlipidemics (ROR 3.65, 95% CI 1.72–7.69) were strongly associated with hospitalizations. In multivariate regression, men, aging (OR 1.02, 95% CI 1.02–1.03), use of antidotes (OR 11.37, 95% CI 6.59–19.62), steroids (OR 5.78, 95% CI 4.71–7.08), and anticoagulants (OR 3.60, 95% CI 2.90–4.46) were independent predictors of drug-induced mortality. Conclusions: This study emphasizes the need for targeted surveillance and risk-mitigation strategies focusing on anticoagulants, steroids and immunosuppressants, particularly among elderly and multimorbid populations. Full article