Moderate Toxicity Research Articles

In silico screening of pomegranate (Punica granatum) and celery (Apium graveolens) metabolites for potential anti-type 2 diabetes activity

Background: Alpha (α)-amylase is a popular pharmacological target for controlling postprandial blood glucose levels. The exploration of natural ingredients for drug development is particularly promising. Notably, pomegranate (Punica granatum) and celery (Apium graveolens) are rich in phenols and flavonoids, making them potential candidates for anti-type 2 diabetes treatments. Objective: This study aims to identify the most promising derivatives from pomegranate and celery using a combined metabolomic and in silico approach. Methods: The study began by identifying metabolites from the KnapSack database, selecting based on primary and secondary metabolites also selecting them based on their pharmacokinetic profile. The selected metabolites were then docked with alpha-amylase (PDB ID: 2QV4). Furthermore, the interactions were analyzed using Discovery Studio, and toxicity profiles were assessed in silico using ECOSAR and Toxtree software. Results: The analysis identified punicaflavone and 2-deoxybrassinolide as the compounds with the highest binding affinity, at -10.06 kcal/mol and -10.89 kcal/mol respectively, both surpassing acarbose’s -9.33 kcal/mol. These compounds interacted with 11 common residues in alpha-amylase, mirroring acarbose’s interactions. In silico toxicity analysis revealed that punicaflavone might pose risks to aquatic organisms but does not exhibit potential as a genotoxic or non-genotoxic carcinogen. Conversely, 2-deoxybrassinolide displayed moderate toxicity to aquatic organisms but was also free from genotoxic and non-genotoxic carcinogenic potential. Conclusion: Punicaflavone and 2-deoxybrassinolide emerged as the most promising compounds, demonstrating strong binding affinities and similar interaction patterns with α-amylase as acarbose. Although both compounds may pose risks to aquatic environments, they do not show potential as genotoxic or non-genotoxic carcinogens, supporting their further exploration as anti-diabetic agents.

Exploring the antileishmanial activity of dicentrine from Ocotea puberula (Lauraceae) using biomembrane models

This study aimed to assess the antiprotozoal efficacy of dicentrine, an aporphine alkaloid isolated from Ocotea puberula, against amastigote forms of Leishmania (L.) infantum. Our findings reveal that dicentrine demonstrated a notable EC50 value of 10.3 μM, comparable to the positive control miltefosine (EC50 of 10.4 μM), while maintaining moderate toxicity to macrophages (CC50 of 51.9 μM). Utilizing an in silico methodology, dicentrine exhibited commendable adherence to various parameters, encompassing lipophilicity, water solubility, molecule size, polarity, and flexibility. Subsequently, we conducted additional investigations to unravel the mechanism of action, employing Langmuir monolayers as models for protozoan cell membranes. Tensiometry analyses unveiled that dicentrine disrupts the thermodynamic and mechanical properties of the monolayer by expanding it to higher areas and increasing the fluidity of the film. The molecular disorder was further corroborated through dilatational rheology and infrared spectroscopy. These results contribute insights into the role of dicentrine as a potential antiprotozoal drug in its interactions with cellular membranes. Beyond elucidating the mechanism of action at the plasma membrane's external surface, our study sheds light on drug-lipid interface interactions, offering implications for drug delivery and other pharmaceutical applications.

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Differential Rates of Toxicity Between Chloroquine and Hydroxychloroquine

Purpose: To describe two cases of patients with systemic lupus erythematosus (SLE) who manifested differential rates of retinal toxicity progression on hydroxychloroquine (HCQ) and chloroquine (CQ), respectively. Methods: Retrospective case reports. Results: Case 1 is a 41-year-old woman with SLE and history of renal involvement, who had been managed on HCQ for 14 years and gradually progressed to moderate retinal toxicity over several years. Case 2 is a 59-year-old woman with SLE and history of renal involvement, who had been managed on quinacrine for 20 years followed by chloroquine for 5 years and initially presented without any evidence of retinal toxicity. One year later, she manifested moderate retinal toxicity. Both cases were screened regularly. In case 1, the diagnosis was missed and toxicity progressed predictably and slowly while on HQ. In case 2, there was no salient pathology on OCT or HVF testing at initial presentation. One year later, there was moderate toxicity. Conclusion: Given the dramatically different rate of progression of retinal toxicity in these two patients, these cases highlight potential gaps in our understanding of retinal toxicity and provide rationale to potentially study rates of retinal toxicity progression in patients on CQ or quinacrine.

Synthesis and biological evaluation of some novel benzoxazin-4-one and quinazolin-4-one derivatives based on anti-inflammatory commercial drugs

Benzoxazine and quinazoline are nitrogen-containing heterocyclic scaffolds found in various biologically active compounds. Due to their diverse biological actions, these heterocyclic rings serve as crucial frameworks for designing medicinal compounds. This study aimed to synthesize and assess in vivo anti-inflammatory, analgesic, and low ulcerogenic potential of a few novel benz[d][1,3]-oxazin-4-one and quinazolinone derivatives. Benzoxazinones (3a-e) were synthesized by cyclizing the carboxylic group (-COOH) of five nonsteroidal anti-inflammatory drugs viz., aceclofenac, ibuprofen, diclofenac, mefenamic acid and ketoprofen (2a-e) with anthranilic acid (1) using dry phosphorus oxychloride (POCl3) in pyridine. The corresponding quinazolinone derivatives (5a-e) were obtained by reacting 3a-e with isonicotinic acid hydrazide (4). Both sets of compounds were evaluated for their anti-inflammatory, analgesic effects, and ulcerogenicity in animal models. Structural characterization was performed using spectral analysis. Among the benzoxazinone derivatives, compound 2-(2-((2,6-dichlorophenyl) amino) benzyl)-4H-benzo[d][1,3]oxazin-4-one (3d) exhibited significant anti-inflammatory activity (62.61% inhibition of rat paw edema) and analgesic activity (62.36% protection in acetic acid-induced writhings) with tolerable gastrointestinal toxicity (2.67 ulcerogenicity index) compared to quinazolinone derivatives. The results of anti-inflammatory and analgesic activities of both the series are comparable with the respective, positive control. Compound 3d, a benzoxazinone-diclofenac hybrid, emerged as a lead molecule with potent anti-inflammatory, analgesic activities and moderate gastric toxicity showcasing the promising potential for further development.

Alocasia macrorrhiza rhizome lectin inhibits growth of pathogenic bacteria and human lung cancer cell in vitro and Ehrlich ascites carcinoma cell in vivo in mice

Cancer and antibiotic resistance represent significant global challenges, affecting public health and healthcare systems worldwide. Lectin, a carbohydrate-binding protein, displays various biological properties, including antimicrobial and anticancer activities. This study focused on anticancer and antibacterial properties of Alocasia macrorrhiza lectin (AML). AML, with a molecular weight of 11.0 ± 1.0 kDa was purified using Ion-exchange chromatography, and the homotetrameric form was detected by gel-filtration chromatography. It agglutinates mouse erythrocytes, that was inhibited by 4-Nitrophenyl-α-d-mannopyranoside. Maximum hemagglutination activity was observed below 60 °C and within a pH range from 8 to 11. Additionally, it exhibited moderate toxicity against brine shrimp nauplii with LD50 values of 321 μg/ml and showed antibacterial activity against Escherichia coli and Shigella dysenteriae. In vitro experiments demonstrated that AML suppressed the proliferation of mice Ehrlich ascites carcinoma (EAC) cells by 35 % and human lung cancer (A549) cells by 40 % at 512 μg/ml concentration. In vivo experiments involved intraperitoneal injection of AML in EAC-bearing mice for five consecutive days at doses of 2.5 and 5.0 mg/kg/day, and the results indicated that AML inhibited EAC cell growth by 37 % and 54 %, respectively. Finally, it can be concluded that AML can be used for further anticancer and antibacterial studies.

Aquatic life criteria of hydrothermal liquefaction wastewater via ecotoxicity test and modeling

Wastewater resulting from hydrothermal liquefaction (HTL-AP) of biowaste is gaining attention as an emerging hazardous material. However, there is a lack of specific and systematic ecotoxicity studies on HTL-AP. This study addresses this gap by conducting acute toxicity tests on HTL-AP using typical aquatic species and integrating these results with predicted toxicity values from interspecies correlation estimation models to establish aquatic life criteria. HTL-AP exhibited significant toxicity with LC50 of 956.12–3645.4 mg/L, but demonstrated moderate toxicity compared to common freshwater pollutants like commercial microbicides, personal care products, and insect repellents. The resulting hazardous concentration for 5 % of species (HC5), the criterion maximum concentration, and the short-term water quality criteria for aquatic were 506.0, 253.0, and 168.7 mg/L, respectively. Notably, certain organisms like Misgurnus anguillicaudatus and Cipangopaludina chinensis showed high tolerance to HTL-AP, likely due to their metabolic capabilities on HTL-AP components. The significant decrease in HC5 values for some HTL-AP substances compared to pure compounds could indicate the synergistic inhibition effects among HTL-AP compositions. Furthermore, according to the established criteria, HTL-AP required significantly less diluted water (13 t) than carbendazim (1009 t) to achieve biosafety, indicating a safer release. This research establishes a preliminary water quality criterion for HTL-AP, offering a valuable reference for risk assessment and prediction in the utilization of HTL-AP within environmental contexts.

Chemotherapeutic prospects of organic extracts of Bornetella nitida from Selayar Island

In this study, we aimed to identify the chemotherapeutic potential of Bornetella nitida, a Dasycladacean that contains various phytochemicals. Phytochemical extraction was performed using gradient maceration with n-hexane, chloroform, ethyl acetate, and methanol. Additionally, toxicity tests as well as antioxidant activity, cytotoxicity, phytochemical, and molecular docking analyses against three main cervical cancer proteins were performed. The B. nitida extracts showed moderate toxicity with LC50 ranging from 116.06 to 713.12 μg mL−1. The free-radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl varied with solvent polarity, exhibiting IC50 values of 22.20, 87.77, 401.55, and 752.08 μg mL−1 when extracted using n-hexane, chloroform, ethyl acetate, and methanol, respectively. Meanwhile, the cytotoxicity against HeLa cells ranged from 281.09 to 1329.33 μg mL−1, with the highest activity shown by the ethyl acetate extract. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of phytochemicals with various bioactivities in the extract, such as L-ascorbic acid 2,6-dihexadecanoate, octadec-9-enoic acid, hexadecatrienoic acid, 2,4-bis(1,1-dimethylethyl)phenol, 9,12-octadecadienoic acid (Z,Z), 1,2-benzenedicarboxylic acid, 2,6,10-trimethyl-14-ethylene-14-pentadecene, and phytol. Docking studies implied that the compounds commonly interact well with the binding site of the target protein. Overall, our results indicate that B. nitida extracts especially ethyl acetate extract can be developed as chemotherapeutic agents.

Cytotoxicity screening of 114 Mongolian plant extracts on liver, colon, breast, and cervix cancer cell lines

A total of 114 Mongolian plant species were subjected to cytotoxicity screening against liver (HepG2), colon (HCT116), breast (MCF7), and cervical (HeLa) cancer cell lines. Among them, ethanolic extracts of Androsace incana, Artemisia rutifolia, Saussurea amara, and Inula salsoloides exhibited remarkable cytotoxicity, with IC50 values below 1.5 μg/mL against at least 2 tested cell lines when treated for 48 hours. Erysimum flavum, Juniperus sibirica, and Stellaria dichotoma demonstrated selective cytotoxicity against specific cancer cell lines. Extracts from 23 plant species, such as Artemisia xerophytica, Ajania trifida, Melandrium brachypetalum, Brachanthemum mongolicum, and Rhinanthus songaricus, showed moderate toxicity. Further research on the phytochemicals and biological activities of these species is crucial for a deeper understanding and potential applications. These screening results of the cytotoxic effects of numerous Mongolian plants could establish a foundational dataset for subsequent comprehensive studies on the screened plants.

Investigation of Antimicrobial Activity and Cytotoxicity of Silver Nanoparticle Synthesized using Dopamine as a Reducing and Capping Agent

AbstractWe present a study focused on the controlled fabrication of silver nanoparticles (AgNPs) through colloidal synthesis, employing dopamine as a reducing and capping agent. By manipulating the concentration of silver nitrate, the production of spherical AgNPs with distinct particle diameters (16, 24, 48, and 74 nm) was achieved. The investigation extended to the evaluation of AgNPs′ impact on human embryonic kidney cells, revealing a concentration‐dependent response. At lower AgNPs concentrations, cell viability remained nearly 100 %, progressively declining with rising AgNPs concentrations. Importantly, the cytotoxic thresholds observed were notably elevated, underscoring the relatively mild to moderate toxicity profile of the nanoparticles. Furthermore, the antimicrobial efficacy of these synthesized AgNPs was probed against E. coli and S. aureus bacterial strains. Notably, the AgNPs exhibited robust antimicrobial activity, with superior performance exhibited by smaller‐sized particles compared to larger ones. Impressively, the minimum inhibitory concentration reached as low as 3.5 μg/mL, indicating their potent antimicrobial potential. The achieved distinct particle diameters, concentration‐dependent cytotoxic responses, and potent antimicrobial efficacy against bacterial strains underscore the multifaceted potential of these nanoparticles. These findings contribute valuable insights for their application in diverse fields, from biomedicine to antimicrobial solutions.

Insights into the Chemistry and Functional Properties of Edible Mushrooms Cropped in the Northeastern Highlands of Puebla, Mexico

Herein, we present an integrative investigation of the nutritional and nutraceutical potential of Lactarius indigo, Clitocybe nuda, Clitocybe subclavipes, Russula delica, Russula brevipes, Clitocybe squamulosa, and Amanita jacksonii, which are edible mushrooms consumed in the northeastern highlands of Puebla, Mexico. The content of protein oscillated from 4.8 to 10.9 g 100 g−1 fresh weight (FW) whereas that of fiber ranged from 8.8 to 19.7 g 100 g−1 FW. The edible species presented low amounts of fat (1.5–3.4 g 100 g−1 FW) and reducing sugars (0.8–2.9 g 100 g−1 FW), whereas the content of vitamin C oscillated from 6.5 to 84.8 mg 100 g−1 dry weight (DW). In addition, four vitamins of B complex (thiamine, riboflavin, vitamin B6, and folate) were determined in different concentrations. A high abundance of potassium (92.3–294.3 mg 100 g−1 DW), calcium (139.1–446.9 mg 100 g−1 DW), and magnesium (81.3–339.1 mg 100 g−1 DW) was determined in most of the edible mushrooms, as well as detectable levels of p-hydroxybenzoic acid (2.2–48.7 mg 100 g−1 DW), protocatechuic acid (0.5–50.8 mg 100 g−1 DW), oleic acid (14.2–98.3 mg 100 g−1 DW), linoleic acid (748–1549.6 mg 100 g−1 DW), and linolenic acid (from 9.1 to 83.6 mg 100 g−1 DW). The total phenol content and antioxidant capacity significantly (p < 0.05) varied among the studied species, and their capacity to inhibit enzymes involved in glucose, lipid, and polyamine metabolism. Nevertheless, the hydroalcoholic extracts from A. jacksonii and L. indigo efficiently inhibited alpha-glucosidase and ornithine decarboxylase (IC50 < 50 µg mL−1), respectively. The evaluation of the same extracts on microorganisms associated with the gastrointestinal tract showed negligible toxicity on probiotics (MIC > 500 µg mL−1) and moderate toxicity against pathogenic bacteria (MIC < 400 µg mL−1). Based on the studied parameters, principal component analysis and orthogonal partial least squares discriminant analysis clustered these edible mushrooms into two main groups with similar biological or chemical properties.

Environmental Impact of Heavy Metals in Soils from Electronic Waste Dumpsite in Southwest Nigeria

The massive influx of electronics into Nigeria has led to environmental challenges due to increase in the production of electronic waste, which causes serious health and pollution problems. This study investigated the level and impact of heavy metals in 30 soil samples from an electronic waste disposal site in southwest Nigeria, using appropriate standard methods. The range concentrations of the heavy metals were 1615 mg/kg Pb, 20 mg/kg Cr, 266.32 mg/kg Ni, 22.39 mg/kg Cd and 242.03 mg/kg Cu at depth 0-15cm while 1453.56 mg/kg Pb, 26.31 mg/kg Cr, 497.11 mg/kg Ni, 17.04 mg/kg Cd and 230.31 mg/kg Cu were observed at depth 15-30 cm. The concentrations of the heavy metals exceeded the allowable limits, except for Cr. The mean degree of contaminations, 18.15 and 14.35, were observed at depths 0-15 and 15-30 cm respectively and indicated considerable and moderate degree of contamination by the heavy metals, respectively. The mean Potential index of 323.52 and 225.79 at depth 0-15 cm and 15-30 cm showed sever toxicity and moderate toxicity, respectively. The I-geo. of Pb at both depths indicated extreme contamination. This study reveals sever potential environmental and health hazards in the neighborhood, ecosystem, and community, and advises that the government should establish a national policy on e-waste and regulate testing of all electronics imported under the names of reuse, donation and recycling, which will halt the importation of e-scraps (e-waste).

Sea Cucumber Viscera Contains Novel Non-Holostane-Type Glycoside Toxins that Possess a Putative Chemical Defense Function.

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem.

Clinical outcomes associated with orphenadrine deliberate self-poisoning: a retrospective poisons centre study

Introduction Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose–toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre. Methods Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity. Results Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210–10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose–toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity. Discussion All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products. Conclusions Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.

Characterization and Biological Activities of the Ulvan Polysaccharide-Rich Fraction Obtained from Ulva rigida and Ulva pseudorotundata and Their Potential for Pharmaceutical Application.

Seaweed from the genus Ulva (Ulvales, Chlorophyta) has a worldwide distribution and represents a potential biomass source for biotechnological applications. In the present study, we investigated the ulvan polysaccharide-rich fraction (UPRF) isolated from two Ulva species (U. rigida and U. pseudorotundata), naturally occurring on the Spanish Mediterranean coast. Chemical characterization of UPRFs was performed in order to explore the polysaccharides' composition. Biological assessments of UPRFs were compared by antioxidant activity and in vitro toxicity tests in the human cell lines: HCT-116 (colon cancer), G-361 (malignant melanoma), U-937 (leukemia), and HaCaT cells (immortalized keratinocytes). Chemical analysis revealed that both UPRFs presented rhamnose as the major relative sugar constituent, followed by glucose in U. rigida and xylose in U. pseudorotundata. Both also presented glucuronic acid, galactose, ribose, and mannose as the remaining monosaccharides. Similar antioxidant activity was obtained, where we observed increased activity in response to increased polysaccharide concentrations. Both UPRFs presented moderate toxicity against HCT-116 cell lines and a selectivity index ≥ 3, suggesting a good potential for use in pharmaceutical products.

Abstract A005: The cause behind the COST – exploring qualitative and quantitative aspects of financial toxicity in women diagnosed with advanced/recurrent endometrial cancer

Abstract Objective: To evaluate the prevalence of financial toxicity in women diagnosed with advanced/recurrent endometrial cancer and describe characteristics and qualitative aspects of financial stressors in this population. Methods: Women diagnosed with advanced/recurrent endometrial cancer at an urban academic center were invited to participate in a mixed-methods study to describe quality-of-life (QOL) and financial toxicity. Participants completed surveys including the EuroQOL-5D-5 (QOL), financial toxicity tool (COmprehensive Score for Financial Toxicity (COST)) and completed an interview inquiring about financial stressors. Descriptive statistics were performed, and interviews were transcribed and analyzed using Atlas.ti to identify themes. Results: Eighty-four women participated in the study reflecting a 90% response rate. Participants were a median age of 67.0 years and 6 (7%) self-identified as Hispanic. Most participants self-identified as White (41, 49%), followed by Black (35, 42%), and multiracial (8, 10%). Forty (49%) participants had advanced stage cancer while 42 (52%) had recurrent cancer, with endometrioid adenocarcinoma (41,50%) represented as the most common histology followed by serous carcinoma (18, 22%), carcinosarcoma (11, 13%), the remaining clear cell carcinoma/mixed/undifferentiated (14, 17%). The median financial toxicity score of the population was 28.0 (IQR: 21-35) out of 44.0, with 38.1% of participants reporting moderate financial toxicity (COST <26) and 8.3% reporting severe financial toxicity (COST <14). Lower financial toxicity scores (indicating poor financial wellness) were associated with younger age (<65yo: 24.0 vs. >65yo: 32.0; p<0.01), Black and multiracial participants compared to white participants (Black: 26.0, multiracial: 16.5, white: 33.0; p<0.05), Hispanic ethnicity (13.5 vs. 30.0; p<0.001), single marital status (26.0 vs. 33.0; p<0.05), and lower education (Less than college: 24.1 vs. college and above: 30.0; p<0.05). On multivariate linear regression, financial toxicity scores were associated positively with older age (B= 6.5, p<0.01) and non-single marital status (B=4.8, p<0.05) but were negatively associated with Hispanic ethnicity (B= -11.4, p<0.05). The median QOL score (health utility score) of the population was 0.80 (IQR: 0.71- 0.85) and this score was positively correlated with better financial wellness (higher financial toxicity score) (R= 0.3, p<0.05). Qualitative analysis of participant interviews found that participants experiencing financial toxicity reported themes of “forced retirement” and “forced work interruptions” (9, 11%) while those with financial wellness praised “quality insurance coverage” (19, 23%). Conclusion: Patients with advanced/recurrent endometrial cancer experience a high rate of financial toxicity. Although limited by sample size, financial toxicity was found to be significantly worse in younger, single, and Hispanic women. Further work to study this at-needs population should be done to identify causes and develop solutions to assist patients with financial stressors. Citation Format: Sarah A. Ackroyd, Gini Fleming, Nada Attia, Cheska Zoleta, Nita K. Lee. The cause behind the COST – exploring qualitative and quantitative aspects of financial toxicity in women diagnosed with advanced/recurrent endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A005.

Synthesis, characterization of Schiff base metal complexes with 1, 3 propanediamine as secondary chelates and their DNA binding, DNA cleavage, cytotoxicity, antioxidant and activities

A series of Cu(II), Co(II), Ni(II), and Zn(II) complexes were synthesised from ternary Schiff base ligand (ts) and 1,3-propanediamine (pda). These complexes were characterised using analytical and spectroscopic techniques. All these metal complexes have an octahedral geometry, which is supported by spectro-analytical experimental data. The fabricated Schiff base coordinates with the metal via imine nitrogen, a phenolic oxygen atom, and carboxylate anion as a monobasic tridentate. Thermal properties were also investigated. Antimicrobial studies were carried out against fungi and pathogenic (bacterial) organisms and a good zone of inhibition was observed irrespective of complexes. Free radical scavenging assays were performed by DPPH and H2O2 methods. The results of these two studies revealed that the Cu(II) and Zn(II) complexes were more active. The binding mode of calf thymus (Ct-DNA) to the metal complexes was analysed by the electronic absorption spectroscopy and viscosity measurement study. The findings revealed that the complex bound with DNA via a groove with electrostatic interactionand the copper complex showed a higher binding constant value. Cytotoxicity of the Schiff base and its complexes were evaluated with the breast cancer (MCF-7) cell line and all complexes exhibited moderate toxicity.

Albuterol as an adjuvant in acute anticholinesterase pesticide poisoning: a randomized, placebo-controlled clinical trial.

Acute anticholinesterase pesticide poisoning is a serious clinical problem, particularly in developing countries. Atropine is the most acceptable treatment for acute anticholinesterase poisoning. However, it only stops fluid production. Albuterol is a beta-2 receptor agonist that can increase fluid removal and speed the return of effective oxygen exchange. This study aims to evaluate the safety and efficacy of nebulized albuterol as an adjuvant therapy in patients with acute anticholinesterase poisoning. This stratified block randomized, single-blinded, placebo-controlled, parallel-group clinical trial was conducted between November 2020 and October 2021. It enrolled 80 patients with acute anticholinesterase pesticide poisoning who were admitted to Tanta University Poison Control Center. Patients were allocated into two groups (40 patients each). The strata were based on the severity of poisoning (moderate and severe). Patients in group I received 10mg of nebulized albuterol. Group II received an equivalent volume of nebulized normal saline. Additionally, standard treatment was provided to both groups. Outcomes included oxygenation, mortality, need for endotracheal intubation and mechanical ventilation, hospital stay duration, time to atropinization, and total doses of atropine and oxime. We found insignificant differences in sociodemographics, exposure characteristics, clinical manifestations, or routine laboratory tests between the studied groups. The median values of oxygen saturation by pulse oximetry were 99% in the albuterol moderate toxicity group and 98% in the control moderate toxicity group. Albuterol significantly improved oxygen saturation in moderate intoxicated patients (P=0.039). Therefore, nebulized albuterol is a safe drug. Moreover, it may improve oxygenation in acute anticholinesterase pesticide poisoning.

CD20 CAR T cells safely and reversibly ablate B cell follicles in a non-human primate model of HIV persistence

CAR T-cell therapies have demonstrated immense clinical successes for B-cell and plasma-cell malignancies. We tested their impact on the viral reservoir in a macaque model of HIV persistence, comparing the function of CD20 CAR T cells between animals infected with simian/human immunodeficiency virus (SHIV) and uninfected controls. We focused on the potential of this approach to disrupt B-cell follicles (BCFs), exposing infected cells for immune clearance. In SHIV-infected animals, CAR T cells were highly functional with rapid expansion and trafficking to tissue-associated viral sanctuaries including BCFs and gut-associated lymphoid tissues (GALT). CD20 CAR T-cells potently ablated BCFs and depleted lymph node-associated T follicular helper (TFH) cells, with complete restoration of BCF architecture and TFH cells following CAR T-cell contraction. BCF ablation decreased the splenic SHIV reservoir but was insufficient for effective reductions in systemic viral reservoirs. Although associated with moderate hematologic toxicity, CD20 CAR T-cells were well tolerated in SHIV-infected and control animals, supporting the feasibility of this therapy in people living with HIV with underlying B-cell malignancies. Our findings highlight the unique ability of CD20 CAR T cells to safely and reversibly unmask TFH cells within BCF sanctuaries, informing future combinatorial HIV cure strategies designed to augment antiviral efficacy.

Real Life Data and Outcome of FOLFIRINOX Use in Metastatic Pancreatic Cancer Patients in General Hospitals in the Netherlands.

Pancreatic cancer is one of the five most common causes of cancer mortality in developed countries. In patients with metastatic disease, the most frequent treatment used is FOLFIRINOX, which is associated with moderate toxicity which could influence quality of life. The efficacy of FOLFIRINOX in a general population in the Netherlands has not been subject of research before, and therefore, this research has been set up in order to investigate what the real-life benefits of FOLFIRINOX are in a population with metastatic pancreatic cancer (mPC) treated in three general hospitals in the Netherlands. The data used in this study was collected by patient records leading to a noninterventional retrospective cohort study. Eighty-six patients, over 18years of age, diagnosed with mPC between the years 2015 and 2022 and treated with FOLFIRINOX at Maasstad Hospital in Rotterdam, Amphia Hospital in Breda, or Catharina Hospital in Eindhoven, were included in the study. Kaplan-Meier models were used in order to represent survival outcomes. The results showed a median overall survival of 228days (IQR 118-355). Only 14.0% (n = 12) completed the first-line treatment, and 51.2% (n = 44) of patients stopped treatment before or during cycle 6. Toxicity is highest, grade 3, after the first cycle but remains high for grade 1 and 2 during all treatment cycles. Survival rates for patient with metastatic pancreatic cancer treated with FOLFIRINOX were worse in our study population than in comparative studies.