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Pharmacokinetics, quantum chemistry, and molecular modeling analysis of six potential drug candidates for Chagas disease: posaconazole, K777, phenarimol derivative, BZTS, isoxazole analog, and derivative of 4-arylaminonoline-3-carbonitrile.

AIM: Chagas disease, caused by Trypanosoma cruzi, lacks safe and effective therapies. This study aimed to prioritize antichagasic candidates … able exposure and a low risk of drug - drug interactions. Toxicity models indicated reduced risk of cardiotoxicity, carcinogenicity and hepatotoxicity compared with the other prototypes. Quantum descriptors supported a stable but reactive electronic structure, with a HOMO - LUMO gap of 2.482 eV. Docking and QM/MM analyses revealed strong binding of BZTS to cruza …

TDH-11 inhibits the proliferation and colonization of colorectal cancer by reducing the activity of HDAC.

Histone deacetylase inhibitors (HDACIs) have demonstrated significant efficacy and minimal toxic side effects in certain hematological tumors. Nevertheless, their utilization in the therapy of solid tumors, including colorectal cancer (CRC), is constrained by the occurrence of adverse effects such as myelosuppression and cardiotoxicity. Therefore, the development of more efficient and safer HDACIs is crucial for managing CRC. Here, the effects of TDH-11 (a novel HDAC inhibitor) and the underlying molecular mechanisms that inhibits the deveolpment and progression of CRC cells were investigated …

Emerging Role of Natural Topoisomerase Inhibitors as Anticancer agents.

Topoisomerases I and II are the functionally two forms of DNA topoisomerase. In anticancer research, novel anticancer chemotherapeutical capable of blocking topoisomerase enzymes have been discovered. Most commonly, topoisomerase causes replication fork arrest and doublestrand breaks, and this is how a clinically successful topoisomerase-targeting anticancer medicines work. Unfortunately, this novel mechanism of action has been linked to the development of secondary malignancies as well as cardiotoxicity. The specific binding locations and mechanisms of topoisomerase poisons have been identifi…

Real-world clinical outcomes of CAR-T therapy from the Montefiore health system in the Bronx.

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed diffuse large B-cell lymphoma (DLBCL) treatment, but data in diverse urban populations remain limited. We report outcomes from a comprehensive cancer center in the Bronx. Montefiore Health System treated 79 DLBCL patients with CAR-T from March 2018 to July 2024. Demographics, comorbidities, socioeconomic factors, and acute complications, including immune effector cell neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS), cardiotoxicity, and pulmonary events, were tabulated. Kaplan-Meier survival analysis was performed …

Severe venlafaxine poisoning successfully rescued with veno-arterial extracorporeal membrane oxygenation: A case report.

BACKGROUND: Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is widely prescribed for the treatment of major depressive disorder. At therapeutic dose, it is generally safe, with a low incidence of adverse effects. However, massive venlafaxine ingestion can cause serious cardiotoxicity, leading to life-threatening arrhythmias. CASE SUMMARY: A 31-year-old woman with a history of depression ingested 14.8 g of venlafaxine along with 6 mg of estazolam and 6 mg of flunitrazepam. On admission, 2 hours post-ingestion, she presented only with mild QTc prolongation. At 4 hours post-ingestion…

Cannabis-Induced Cardiac Arrest in a Young Adult: A Case Report.

BACKGROUND Tetrahydrocannabinol (THC), the psychoactive compound in cannabis, is increasingly used recreationally, especially among young ad … diovascular risk factors. Clinicians should maintain a high index of suspicion for cannabis-induced cardiotoxicity in similar presentations, particularly as cannabis use becomes more widespread.

Composite additive manufacturing for suspended microelectrode arrays: Advancing oriented myocardial tissue culturing and electrophysiological sensing.

Microelectrode arrays (MEAs) have ushered in a new era of in vitro drug screening and cardiotoxicity evaluation. However, the morphological constraints of two-dimensional (2D) planar culture and the mechanical rigidity of conventional electrodes hinder the formation of myocardial tissues that closely resemble native physiological conditions and limit the accuracy of drug efficacy analysis based on electrophysiological signals. Here, we present a flexible MEA platform enabled by a composite additive manufacturing approach, with key steps including melt electrowriting of microfibers, electrostat…

Toxicological assessment of cyclopiazonic acid and aflatoxin B1: EFFECTS on zebrafish development and cardiac physiology.

Mycotoxins such as Aflatoxin B1 (AFB1) and Cyclopiazonic Acid (CPA) pose serious health risks, yet their combined toxicity remains poorly un … on cardiac function. Co-exposure, however, further suppressed cardiac function, revealing enhanced cardiotoxicity. These results highlight the amplified risks of co-exposure to CPA and AFB1 and emphasize the need to account for multi-mycotoxin interactions in food safety assessments. The study also reinforces the value of zebrafish embryos as an in vivo model f …

Ibogaine: Revisiting an Ancient Alkaloid for Modern Opioid Dependence.

BACKGROUND: Ibogaine is a naturally occurring hallucinogenic alkaloid originally used in ritualistic ceremonies by West Central African trib … on nicotinic acetylcholine receptors in the ventral tegmental region of the midbrain. Regarding its cardiotoxicity, ibogaine has shown to cause QTc prolongation leading to polymorphic ventricular tachycardia with cardiac arrest in one case. However, in an observational cohort study that included 30 participants, no serious adverse events occurred while taking ib …

Real-world cardiac events and outcomes in cBTKi-treated chronic lymphocytic leukemia patients.

AIM: To evaluate the real-world incidence of cardiovascular adverse events (CVAE) and clinical outcomes among patients with chronic lymphocy … tinib) and 72% (ibrutinib) at 12-months. CONCLUSIONS: Despite improvements in 2nd-generation cBTKi cardiotoxicity, patients with CLL/SLL receiving cBTKis have a considerable cardiovascular disease burden. These findings highlight the unmet need for CLL/SLL treatment options with improved efficacy and safety profiles.

Identification of potential VP40 inhibitor of Marburg virus through molecular docking, pharmacokinetic analysis and molecular dynamics simulation.

West Africa has been experiencing a resurgence of Marburg virus disease (MVD), a zoonotic pathogen that causes severe hemorrhagic fever in b … (average 3.50 bonds), suggesting stronger binding. Procyanidin's superior drug-likeness, decreased cardiotoxicity, and decreased carcinogenicity potential were all shown by ADMET analysis. Its higher binding energy (- 57.82 KJ/mol) was further validated by free energy calculations (MM-PBSA). According to these results, procyanidin, a natural substance shows pro …

Тирозиновая киназа Брютона - новая цель для иммунной медиации подстрекательских заболеваний?

Тирозиновая киназа Брютона (BTK) — цитоплазмический белок, играющий ключевую роль в сигнализации каналов вниз по течению различных поверхностных рецепторов в клетках В и миелиоидных клетках. К ним относятся сам рецептор B-клеток, рецепторы Fc, включая Fc RI, рецепторы, похожие на платные, и рецепторы химокина. Врожденный недостаток BTK вызывает агаммаглобулинамию, связанную с X, из-за блока развития B-клеток, а ингибиторы BTK (BTKi) утверждаются для лечения некоторых магнелезных свойств B-клеток. Они также изучались в связи с различными аутоиммунными и подстрекательскими заболеваниями. В реумн

Совпадение в аннотации оригинала
Bruton's tyrosine kinase (BTK) is a cytoplasmic protein that plays a key role in signalling pathways downstream of diverse surface receptors … ere allergic disease such as food allergy. First generation BTKi had a safety profile that included cardiotoxicity, hypertension, haemorrhage and rash. Second generation inhibitors have a more acceptable safety profile although dose-limiting toxicity is still observed in some conditions, including RA. Pharmacokinetic factors aside, the variable efficacy in diffe …

Early Impact of Mobilization Process on Cardiac Function and Size in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Background: The hematopoietic stem cell transplantation (HSCT) process is known to cause cardiac toxicity of different grades. In this paper … associated with reduced RV systolic function. S' could be used as a reliable tool to evaluate early cardiotoxicity in HSCT patients and guide further follow-up.

Toxicity of pesticide cocktails in amphibian larvae: understanding the impact of agricultural activity on aquatic ecosystems in the Salado River basin, Argentina.

Aquatic communities are increasingly exposed to complex mixtures of contaminants, mainly pesticides due to the impact of agricultural activi … ive stress, and impairments in detoxification and hepatic functioning. Neurotoxicity, genotoxicity, cardiotoxicity and high mortality under stress conditions were also observed in exposed larvae. This novel evaluation highlights the ecotoxicological risk for aquatic organisms exposed to complex mixtures and underscores the need to consider cocktail effects in st …

Optimizing Nav1.7-Targeted Analgesics: Revealing Off-Target Effects of Spider Venom-Derived Peptide Toxins and Engineering Strategies for Improvement.

The inhibition of Nav1.7 is a promising strategy for the development of analgesic treatments. Spider venom-derived peptide toxins are recogn … its inhibition of hNav1.7 while significantly reducing its inhibition of rKv4.2/4.3 and eliminating cardiotoxicity. Moreover, mGpTx1-SA demonstrates potent analgesic effects in both inflammatory and neuropathic pain models, accompanied by an improved in vivo safety profile. The results suggest that off-target inhibition of rKv4.2/4.3 by specific spider peptide t …

Gypenoside A-loaded mPEG-PLGA nanoparticles ameliorate high-glucose-induced retinal microvasculopathy by inhibiting ferroptosis.

Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum, and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. Thi…

A comparative analysis of daunorubicin and its metabolite daunorubicinol interaction with apoptotic and drug resistance proteins using in silico approach.

Daunorubicin (DNR) is a chemotherapeutic drug associated with multiple side effects, including drug resistance. As the molecular mechanism r … associated with apoptosis while DAUNol mainly targeted pathways related to multidrug resistance and cardiotoxicity. Overall, the results highlight that DNR biotransformation reduces its capability to induce apoptosis while enhancing its ability to induce drug resistance and off-target toxicity.Communicated by Ramaswamy H. Sarma.

NMNATs expression inhibition mediated NAD+ deficiency plays a critical role in doxorubicin-induced hepatotoxicity in mice.

Doxorubicin (DOX) is one of the most widely used antineoplastic drugs with known cardiotoxicity while other organ toxicity, such as hepatotoxicity is not well defined. This study was to explore the role of nicotinamide adenine dinucleotide (NAD+) in DOX-induced hepatotoxicity. DOX (20 mg/kg) induced acute liver injury and oxidative stress in C57BL/6 J mice at 48 h. Notably, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H dehydrogenase quinone 1 (NQO1) were downregulated. NAD+ deficiency was confirmed due to DOX exposure. Mechanistically, the downregulation of n…

Tramadol as a Voltage-Gated Sodium Channel Blocker of Peripheral Sodium Channels Nav1.7 and Nav1.5.

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been sh … dy, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Nav1.7 or show cardiotoxicity by blocking Nav1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

Polystyrene nanoplastics induce developmental impairments and vasotoxicity in zebrafish (Danio rerio).

The exponential use of plastics has significantly increased environmental pollution by nanoplastics (NPs). In the aquatic environment, NPs i … at 34 ng L-1 and 34 μg L-1 induced neurotoxicity (decreased frequency of spontaneous contractions), cardiotoxicity (bradycardia), and morphological changes in the eyes and head, indicating that PS-NPs induce developmental impairments in zebrafish. In addition, cytotoxicity in the caudal region (34 ng L-1), ROS production, decreased mean swimming speed, and dista …