Poisoning Research Articles

Visible-light-induced degradation of rhodamine B by double Z-scheme magnetic ATP-g-C3N4/SnFe2O4/Bi2WO6 heterojunctions: Performance and mechanism

A magnetic ternary double Z-scheme ATP-g-C3N4/SnFe2O4/Bi2WO6 (AG/SFO/BWO) heterojunction was prepared by a simple and green hydrothermal process, which was successfully used in the dye degradation. AG/7.5 %SFO/BWO catalyst demonstrated outstanding visible-light-induced degradation, achieving an impressive 96.72 % degradation of rhodamine B (RhB) in 2 h. Compared with Bi2WO6 (BWO) and SnFe2O4/Bi2WO6 (SFO/BWO), the degradation efficacy was increased about 1.65 and 1.16 times, respectively. After being used for five batches, the degradation rate of RhB remained over 90 %. Moreover, AG/7.5 %SFO/BWO showcased remarkable efficacy in degrading methylene blue (MB), Congo red (CR), and tetracycline (TC). Bacterial toxicity test indicated the toxicity of dyes was rapidly decreased in 24 h. Physicochemical properties and morphological characteristics of the prepared photocatalysts were investigated by various methods, including XRD, FTIR, XPS, SEM, TEM, BET, VSM, UV–vis, and EIS. AG/7.5 %SFO/BWO, utilizing a dual-Z scheme pathway, efficiently absorbed broad light, yielding multiple active agents, primarily hole (h+) and superoxide radical •O2−. The double Z-scheme heterojunction structure enhanced the electron-hole separation and ensured a stable photochemical environment. UPLC-HRMS was used to identify intermediates during the RhB degradation. Its degradation pathway and catalytic mechanism were illustrated systematically. The bio-toxicity (acute toxicity, developmental toxicity, and mutagenicity) of the intermediates was also evaluated by T.E.S.T.

Safety, Analgesic, and Anti-Inflammatory Effects of Aqueous and Methanolic Leaf Extracts of Hypericum revolutum subsp. keniense

In light of the enduring obstacles encountered in analgesia and anti-inflammatory therapeutics despite the strides made in contemporary medical sciences, the quest for alternative efficacious strategies is an imperative pursuit. Thus, this study investigated the safety profiles, as well as the analgesic and anti-inflammatory attributes, of aqueous and methanolic leaf extracts derived from Hypericum revolutum subsp. keniense—a botanical entity entrenched in historical ethnomedicinal practices in the Kenyan context. The assessment of acute oral toxicity of these extracts was conducted in accordance with the Up- and-Down method advocated by the Organisation for Economic Cooperation and Development (OECD), utilizing Swiss albino mice as the experimental subjects. Subsequent investigation entailed the evaluation of antinociceptive and anti-inflammatory properties employing the acetic acid-induced writhing and carrageenan-induced paw oedema methodologies, respectively, in the same murine model. The findings of this study evince the safety of both aqueous and methanolic extracts, with LD50 values surpassing 2000 mg/kg body weight and the absence of discernible signs of toxicity. Furthermore, a notable dose-dependent (P<0.05) manifestation of analgesic effects was observed for both extracts, with the aqueous variant demonstrating heightened potency compared to its methanolic counterpart (P<0.05). Moreover, the anti-inflammatory efficacy escalated significantly with escalating extract doses and prolonged treatment duration (P<0.05), wherein the aqueous extract showcased superior effectiveness vis- à-vis the methanolic extract across all dosage regimens and temporal checkpoints (P<0.05). Therefore, this investigation underscores the latent promise of the examined extracts as reservoirs of safe and efficacious analgesic and anti-inflammatory agents, thereby meriting further meticulous exploration. Subsequent research endeavours ought to pivot towards elucidating the phytochemical constituents underpinning the observed effects, alongside unravelling their mechanistic underpinnings across a spectrum of animal models and clinical milieus.

Antimicrobial and Antiplasmodial Activities of Endophytic Fungi Associated with Psidium guajava

Infections due to antimicrobial-resistant microorganisms have become widespread in recent years. Thus, searching for novel antimicrobial agents to combat such pathogens has become crucial. The current study aimed to evaluate the antimicrobial, antiplasmodial, and immunomodulatory activities of the extracts of endophytic fungi isolated from Psidium guajava. Isolation, identification, fermentation, and extraction of the secondary metabolites of the fungal endophytes were carried out following standard procedures. The extracts were subjected to High-Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis to detect their bioactive components. The Antimicrobial activity and Minimum Inhibitory Concentration of the fungal extracts were evaluated against pure cultures of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia using Agar well diffusion and Agar dilution method respectively. The acute toxicity study (LD50) was carried out using Lorke’s method. The extracts were tested in vivo in mice for antiplasmodial activity against Plasmodium berghei and in vitro against Plasmodium falciparum using Peter and Reyley's curative test method and WHO standardized micro-test system with modification respectively. The immunomodulatory activity of the extracts was evaluated by cyclophosphamide-induced myelosuppression (hematological parameters). Active extracts were further subjected to Delayed-Type Hypersensitivity Response (DTHR) and Haemagglutination Inhibition Assay using Sheep Red Blood Cells as antigens. The result showed Alternaria sp. (PGL1, PGL2, PGL3), from P. guajava. The HPLC-DAD analysis revealed the presence of bioactive compounds previously reported to have antimicrobial, antiplasmodial, and immunomodulatory properties. The fungal extracts exhibited varying degrees of antimicrobial activity. The LD50 of the fungi extracts was>5000 mg/kg in mice. The extracts at 100 and 200 mg/kg body weight in mice showed varying degrees of antiplasmodial activity. Growth of P. berghei was significantly (p<0.001) inhibited, curative effect ranges from 59.09 – 100%. Schizont maturation of P. falciparum isolates was inhibited and the highest level of inhibition was observed at 1 mg/ml (p<0.05). The fungal extracts reversed the effect of cyclophosphamide-induced reduction in total white blood cell counts and % neutrophil. This study showed that the tested plant harbors species of endophytic fungi that contain numerous secondary metabolites. The endophytic fungi showed prophylactic, immunostimulatory, and antiplasmodial activities, which can be exploited to develop antimicrobial, antiplasmodial, and immunomodulatory agents.

Ecotoxicological Assays with the Calanoid Copepod Acartia tonsa: A Comparison between Mediterranean and Baltic Strains

The use of marine invertebrates in ecotoxicology is important for an integrated approach which takes into consideration physiological responses and chemical levels in environmental matrices. Standard protocols have been developed and organisms belonging to different trophic levels are needed as model organisms to evaluate toxicant bioavailability and assess their impact on marine biota. The calanoid copepod Acartia tonsa is commonly used in ecotoxicology due to its widespread distribution and well-studied biology. However, different strains coming from various geographical areas are available, and possible variations in physiological characteristics raise concerns about the comparability of ecotoxicological results. This study compares the life cycle assessment and sensitivity of Adriatic and Baltic strains of A. tonsa exposed to nickel (Ni2+) in standardized acute and semi-chronic tests. Life cycle assessments revealed differences in egg production, egg-hatching success, and naupliar viability between the strains. The acute toxicity test demonstrated the significantly higher sensitivity of Adriatic strain nauplii to Ni2+ compared to the Baltic strain, whereas the semi-chronic test showed no significant difference in sensitivity between the strains. These findings suggest that while strain-specific differences exist in different geographical populations, responses to toxicants are not significantly different. Particularly, the semi-chronic assessments with both A. tonsa strains emphasized the robustness of this species as a model organism in ecotoxicology.

Bioassay Study of Azadirachtin And Plumbagin on Pericallia ricini (Lepidoptera: Arctiidae)

In recent years, the overuse of commercially obtainable synthetic pesticides against phytophagous insects has augmented their bioaccumulation in the biosphere, foremost to increased resistance and reduced soil biodiversity. Moreover, extreme uses of insecticides enter various environmental resources as an outcome of overflow, initiating deleterious health problems to agriculturalists and consumers of agricultural products. Hence, more attention is being paid towards the expansion of substitute eco-friendly insecticides that will help in an effective pest management system and also prevent longstanding exposure that causes diseases. As a result, important ecologically friendly and harmless alternative practice strategies to artificial compounds are essential. Azadirachtin and plumbagin (phytoproducts) have been identified as an extraordinary biocontrol agent with low toxicity and high efficacy among many plant products for latent chemotherapeutic compounds in plant pest and disease management systems. The biocidal effectiveness of neem is attributed to its azadirachtin active ingredient, which affect some metabolic processes in insects such as protein synthesis, deviations in biological fitness, reduced sexual communication, and chitin synthesis. Similarly, Plumbagin (Napthaquinones) have established substantial attention in agricultural chemistry because of a novel action mode, extremely high activity against a broad spectrum of insects, low acute toxicity to mammals, and environmentally benign characteristics. The present study indicated that Azadirachtin and Plumbagin can be significant alternatives to Chemical insecticides for Pericallia ricini control in short-cycle crops.

An in vitro study of metformin adsorption to activated charcoal

Introduction Metformin is a biguanide used to manage patients with type 2 diabetes mellitus. However, metabolic acidosis with an elevated lactate concentration and death caused by metformin overdoses are toxicological concerns. Although activated charcoal has been widely used for gastrointestinal decontamination in cases of acute poisoning, there is no evidence regarding its efficacy in treating metformin overdoses. We therefore evaluated the adsorptive capacity of activated charcoal for metformin in vitro. Methods Activated charcoal (specific surface area: 1,080 m2/g) mixed with various concentrations of metformin solution was dissolved in simulated gastric and intestinal fluids at 37° Celsius. The suspension was then filtered and the metformin concentration in the filtrate was determined using high-performance liquid chromatography. The maximum adsorptive capacity for metformin was calculated using the Langmuir adsorption isotherm equation. Results The amount of metformin adsorbed per gram of activated charcoal ranged from 0.7 to 8.1 mg/g at pH 1.2, and from 8.4 to 48.2 mg/g at pH 6.8. The corresponding maximum adsorptive capacities were 10.6 mg/g and 55.9 mg/g respectively. Discussion The maximum adsorptive capacity of activated charcoal for metformin was similar to that of its capacity for other poorly adsorbed substances. This is likely because metformin is water-soluble and has high polarity—factors that correlate with poor adsorption on activated charcoal. Conclusions The maximum adsorption of metformin by activated charcoal was low. Therefore, activated charcoal may not be effective for treating patients with metformin overdose.

WITHANICANDRIN ISOLATED FROM Datura Ferox PROMOTES ANTINOCICEPTION BY MODULATING THE ASICS AND TRPS CHANNELS AND ANTI-INFLAMMATION IN ADULT ZEBRAFISH.

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i.p.) with withanicandrin (4; 20 and 40 mg/kg; 20 μL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5% and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

Dosimetric and toxicity comparison between Syed-Neblett and Fletcher-Suit-Delclos Tandem and Ovoid applicators in high dose rate cervix cancer brachytherapy

PURPOSETo compare patient and tumor characteristics, dosimetry, and toxicities between interstitial Syed-Neblett and intracavitary Fletcher-Suit-Delclos Tandem and Ovoid (T&O) applicators in high dose rate (HDR) cervical cancer brachytherapy. METHODSA retrospective analysis was performed for cervical cancer patients treated with 3D-based HDR brachytherapy from 2011 to 2023 at a single institution. Dosimetric parameters for high-risk clinical target volume and organs at risk were obtained. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTSA total of 115 and 58 patients underwent Syed and T&O brachytherapy, respectively. Patients treated with Syed brachytherapy were more likely to have larger tumors and FIGO stage III or IV disease. The median D2cc values to the bladder, small bowel, and sigmoid colon were significantly lower for Syed brachytherapy. Patients treated with Syed brachytherapy were significantly more likely to be free of acute gastrointestinal (44% vs. 21%, p = 0.003), genitourinary (58% vs. 36%, p = 0.01), and vaginal toxicities (60% vs. 33%, p = 0.001) within 6 months following treatment compared to patients treated with T&O applicators. In contrast, Syed brachytherapy patients were more likely to experience late gastrointestinal (68% vs. 49%, p = 0.082), genitourinary (51% vs. 35%, p = 0.196), and vaginal toxicities (70% vs. 57%, p = 0.264). CONCLUSIONSSyed-Neblett and T&O applicators are suitable for HDR brachytherapy for cervical cancer in distinct patient populations. Acute toxicities are more prevalent with T&O applicators, while patients treated with Syed-Neblett applicators are more likely to develop late toxicities.

Antihypertensive Potential of Japanese Quail (Couturnix Couturnix Japonica) Egg Yolk Oil (QEYO) in Sprague Dawley Rats.

Oils from animal sources have been used for centuries in the management of diseases. This research was conducted to screen the ex vivo and in vivo toxicity of quail egg yolk oil (QEYO) extracts and assess their effects on the management of hypertension in rats. QEYO was extracted using gentle heating (GH) and n-hexane (NHN). The extracts were subjected to toxicity testing using the hen's egg test on chorioallantoic membrane (HET-CAM) and bovine corneal histology test. Acute and sub-chronic toxicity (28 days) were evaluated in rats. Hypertension was induced in rats by administering 80 mg/kg of Nω-L-Arginine Methyl Ester (L-NAME) per day for 28 days. Treatments commenced on the 14th day; Nifedipine at 30 mg/kg and 1 mL of distilled water were administered as positive and negative controls. Blood pressure (BP), lipid profiles, and oxidative stress markers were quantified. No irritation was observed using the HET-CAM test in the egg treated with both extracts. Bovine corneal histology showed no lesions in all treated groups. No signs of toxicity were observed in either acute or sub-chronic toxicity studies. A significant reduction in blood pressure was observed in rats treated with the extracts (p < 0.05). Changes in total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDLPs), and high-density lipoproteins (HDLPs) were not significant compared to the control (p > 0.05). Oxidative stress markers (SOD and CAT) increased significantly in the treated groups compared to the control, while the malondialdehyde levels decreased (p < 0.05). QEYO was safe in both ex vivo and in vivo studies and can be said to have the potential to lower blood pressure as well as cardio-protective effects in hypertensive rats. This research provides evidence based on which QEYO could be used safely as an adjuvant therapy in eye drops and cosmetics and can be considered an effective choice for preventing hypertension.

Acute Toxicity of the Lampricide 4-Nitro-3-(trifluoromethyl)phenol to the Mussel (Obovaria subrotunda), Its Host (Percina maculata), and a Surrogate Mussel Species (Obovaria olivaria).

The risk of lampricide applications (such as 4-nitro-3-[trifluoromethyl]phenol [TFM]) to nontarget fauna continues to be a concern within the Great Lakes Fishery Commission Sea Lamprey Control Program, especially among imperiled aquatic species-such as native freshwater mussels. The Grand River (Ohio, USA) is routinely treated for larval sea lampreys (Petromyzon marinus), and this river contains populations of the federally threatened mussel Obovaria subrotunda. Given this spatial overlap, information on the sensitivity of O. subrotunda to TFM is needed. Our objectives were to assess the toxicity of TFM to (1) adult Obovaria olivaria (a surrogate for O. subrotunda), (2) glochidial larvae of O. olivaria and O. subrotunda, (3) juveniles of O. olivaria and O. subrotunda, and (4) adult Percina maculata (host for O. subrotunda glochidia). In acute toxicity tests, TFM was not toxic to glochidia and adult mussels at exposure concentrations that exceed typical treatment rates. Although significant dose-response relationships were observed in hosts and juveniles, survival was ≥95% (Percina maculata), ≥93% (O. olivaria), and ≥74% (O. subrotunda) at typical treatment rates. However, the steep slope of these dose-response relationships indicates that an approximately 20% difference in the treatment level can result in nearly an order of magnitude difference in survival. Collectively, these data indicate that routine sea lamprey control operations are unlikely to acutely affect these species or their host. However, given that many mussel species are long-lived (30-100 years), the risks posed by lampricide treatments in the Great Lakes would be further informed by research on the potential long-term effects of lampricides on imperiled species. Environ Toxicol Chem 2024;00:1-8. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation on the traditional safe use of Kochiae Fructus oriented by antioxidant properties and oral safety of its ethanolic extract

Kochiae Fructus (KF) is a traditional Chinese medicine, which has been used to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. In order to fully understand the traditional medicinal value of KF, we evaluated the antioxidant properties and oral safety of its ethanolic extract. Considering flavonoids and phenolics in medicinal plants generally have strong antioxidant activity, we firstly detected the total flavonoids and phenolics contents of KFEE and its fractions. Secondly, we evaluated the antioxidant activities of KFEE and its fractions. Finally, we evaluated the oral safety of KFEE by the acute and 28-day subacute toxicities. The n-butanol fraction (ENBF) possessed the highest phenolics and flavonoids with values of 77.30 ± 3.17 mg gallic acid equivalents/g and 228.81 ± 7.56 mg rutin equivalents/g, respectively. The results of antioxidant tests showed that ENBF possessed potent antioxidant ability. Among them, the high antioxidation capacity observed in ENBF could be attributed to its rich content of flavonoids and phenolics. The results of toxicological studies showed that the LD50 value of KFEE was 6000 mg/kg BW, and the no observed adverse effect level (NOAEL) of KFEE was 600 mg/kg BW. According to the standards of the American Academy of Sciences for the classification of toxic substances, KFEE can be classified as practically non-toxic substance, which provided valuable evidence for the oral safety of KF as a natural aging delay medicine.

Extreme hypofractionated stereotactic radiotherapy for localized prostate Cancer: Efficacy and late urinary toxicity according to transurethral resection of the prostate history

Background and purposeExtreme hypofractionated stereotactic body radiotherapy (SBRT) is a therapeutic alternative for localized low- or intermediate-risk prostate cancer. Despite the availability of several studies, the toxicity profile of SBRT has not been comprehensively described. This real-world evidence study assessed the efficacy and toxicities associated with this regimen, and potential prognosis factors for genitourinary toxicities. Materials and methodsThis retrospective study included 141 consecutive patients with localized prostatic adenocarcinoma treated with CyberKnife™ SBRT, as primary irradiation, at the Oscar Lambret Center between 2010 and 2020. The prescribed dose was 36.25 Gy in 5 fractions. Acute and late toxicities were graded according to the CTCAE (version 5.0). Biochemical recurrence-free survival (bRFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The cumulative incidence of biochemical recurrence (cBR) was estimated using the Kalbfleisch–Prentice method. ResultsAmong the included patients, 13.5 % had a history of transurethral resection of the prostate (TURP). The median follow-up was 48 months. At 5 years, bRFS, cBR, and OS were 72 % (95 %CI: 61–81), 7 % (95 %CI: 3–14), and 82 % (95 %CI: 73–89), respectively. Twenty-nine patients experienced at least one late toxicity of grade ≥ 2; genitourinary (N = 29), including 3 cases of chronic hematuria, and/or gastrointestinal (N = 1). The cumulative incidence of late urinary toxicity of grade ≥ 2 was 20.6 % at 5 years (95 %CI: 13.9–28.1). Multivariate analysis revealed that a history of TURP was significantly associated with late urinary toxicity of grade ≥ 2, after adjusting for clinical target volume (Odds Ratio = 3.06; 95%CI: 1.05–8.86; P = 0.04). ConclusionExtreme hypofractionated SBRT is effective for localized prostate cancer with a low risk of late toxicity. A history of TURP is associated with a higher risk of late urinary toxicity. These findings may contribute to the optimal management of patients treated with this regimen, particularly those with a history of TURP.

The chemical composition, protective effect of Rheum officinale leaf juice and its mechanism against dextran sulfate sodium-induced ulcerative colitis

BackgroundRhubarb is widely distributed and cultivated worldwide, and its leaves presented antioxidant activity and could be used as food additive. However, the chemical ingredients, and protective effect of Rheum officinale leaf juice (JROL) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) are still unclear. PurposeThis paper sought to the characterization and functional properties of JROL, and explore the underlying mechanism on UC mice. MethodsUPLC-ESI-Q-TOF/MS and other analytical instruments were employed to determine the chemical ingredients of JROL. After inducing UC model using 3% DSS, multiple biological methods were used to evaluate its protective effect and the potential mechanism. ResultsJROL is rich in proximate compositions and minerals and has high nutritional value, and contains reducing sugars, polysaccharides and pectin. Fifteen compounds were identified using UPLC-ESI-Q-TOF/MS. Among them, rutin has the highest content (2.22 %) in UPLC analysis. JROL presented protective effect on DSS-induced UC, and alleviated morphological alterations and ultra-structural feature of tissue, and the polysaccharides and flavonoids may contribute to its protective effect. JROL inhibited NF-κB/NLRP3 signaling pathway to alleviate inflammatory response, oxidative stress and intestinal injury by decreasing the expression of p-p65, p-IκBα, NLRP3, ASC, etc.. Moreover, it up-regulated the expression of tight junction proteins, and re-balanced the disturbance of gut microbiota to regulate the inflammatory response. Finally, a correlation among the inflammatory response, NF-κB/NLRP3 pathway and gut microbiota was established. Moreover, JROL presented the safety in the acute toxicity test. ConclusionJROL could be used as a potential new source for treating UC.

Pioglitazone Nanoparticles Development, Characterization, Optimization, and a Zebrafish Model Evaluation of its Teratogenic Safety

Background: New nanoparticles (NPs) and biomaterials are utilized more frequently in biological research for vaccinations, diagnostic procedures, and drug administration. Nanomaterials are materials with d50 value from 1 to 100nm. They are also found in various consumer goods, the environment, and work. Thus, it has become crucial for the appropriate development of nanotechnology to assess the safety and potential therapeutic applications of these nanomaterials. The BCS Cass II medication pioglitazone hydrochloride, used to treat hypoglycaemia, has poor bioavailability after oral treatment because it dissolves poorly in gastrointestinal fluids. background: New nanoparticles and biomaterials are utilized more frequently in biological research for vaccinations, diagnostic procedures, and drug administration. They are also found in various consumer goods, the environment, and work. Thus, it has become crucial for the appropriate development of nanotechnology to assess the safety and potential therapeutic applications of these nanomaterials. The BCS Cass II medication pioglitazone hydrochloride, used to treat hypoglycaemia, has poor bioavailability after oral treatment because it dissolves poorly in gastrointestinal fluids. Objective: This study aimed to create adjusted pioglitazone nanoparticles to decrease dose-related side effects and prolong its release when used against type 2 diabetes. objective: This study aimed to create adjusted pioglitazone nanoparticles to decrease dose-related side effects and prolong its release when used against type 2 diabetes Methods: The emulsion solvent evaporation approach was used to create nanoparticles utilising HPMC K15M and Eudragit S100 as polymers, and Tween 80 as a surfactant. On framed nanoparticles, in-vitro evaluation approaches for drug-polymer compatibility, percentage yield, particle size, zeta potential, polydispersity index, surface morphology, encapsulation effectiveness, and in-vitro drug release study were used, followed by in-vivo acute toxicity experiment. Conclusion: From the obtained data, it can be said that a suitable optimized formulation of pioglitazone nanoparticles was prepared, which offered extended drug release of 95% in 10 hours.

N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system.

Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects. To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF3SePB) in mice and the involvement of the serotonergic and noradrenergic systems. Male Swiss mice were treated with CF3SePB (1-50mg/kg, i.g.) and 30min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50mg/kg, i.g.), and after 30min of CF3SePB administration the FST was performed. CF3SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice. This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

Prediction of acute toxicity for Chlorella vulgaris caused by tire wear particle-derived compounds using quantitative structure-activity relationship models

Tire wear particles (TWPs) enter aquatic ecosystems through various pathways, such as rainwater and urban runoff. Additives in TWPs can harm aquatic organisms in these ecosystems. Therefore, it is essential to investigate their toxicity to aquatic organisms. In our study, we initially recorded the median effective concentrations of 21 TWP-derived compounds on Chlorella vulgaris growth, ranging from 0.04 to 8.60 mg/L. Subsequently, through an extensive review of the literature, we incorporated 112 compounds with specific toxicity endpoints to construct the QSAR model using genetic algorithm and multiple linear regression techniques, followed by the construction of the consensus model and the quantitative read-across structure-activity relationship (q-RASAR) model. Meanwhile, we employed rigorous internal and external validation measures to assess the performance of the model. The results indicated that the developed q-RASAR model exhibited strong adaptation, robustness, and reliable prediction, with q-RASAR indicators of Q2LOO = 0.7673, R2tr = 0.8079, R2test = 0.8610, Q2Fn = 0.8285−0.8614, and CCCtest = 0.9222. Based on an external dataset containing 128 emerging TWP-derived compounds, the model's applicability domain coverage was 90.6 %. The q-RASAR model predicted that the structure of diphenylamine was associated with higher toxicity, possibly liked to the SpMax2_Bhm and LogBCF descriptors. The established model reliably provides prediction and fills a critical data gap. These findings highlight the potential risks posed by emerging TWP-derived compounds to aquatic organisms.

Synergistic developmental effects of zebrafish exposed to combined perfluorooctanoic acid and atrazine

Perfluorooctanoic acid (PFOA) and atrazine are two endocrine disruptors that are widely found in waters. Negative effects of PFOA and atrazine have been studied individually, but few data have focused on their combined effects. Here, zebrafish embryos were used as model to investigate the combined toxicity of PFOA and atrazine. The acute toxicity of atrazine (11.9 mg/L) to zebrafish embryos was much higher than that of perfluorooctanoic acid (224.6 mg/L) as shown by the 120h-LC50 value. Developmental effects, including delayed yolk sac absorption, spinal curvature, and liver abnormalities, were observed in both one- and two-component exposures. Notably, the rate of embryonic malformations in the co-exposure group was more than twice as high as that of single component exposure in the concentration range of 1/8-1/2 EC50, which indicated a synergistic effect of the binary mixture. The synergistic effect of PFOA-atrazine was further validated by combinatorial index (CI) modeling. In addition, changes of amino acid metabolites, reactive oxygen species and superoxide dismutase indicated that oxidative stress might be the main pathway for enhanced toxicity under co-exposure condition. Overall, co-exposure of PFOA and atrazine resulted in stronger developmental effects and more complicated amino acid metabolic response toward zebrafish, compared with single component exposure.

Essential oil from Cinnamomum cassia Presl bark regulates macrophage polarization and ameliorates lipopolysaccharide-induced acute lung injury through TLR4/MyD88/NF-κB pathway

Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-κB pathway was elucidated. BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-α-muurolene, δ-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-α, IL-6, and IL-1β in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/MyD88/NF-κB signaling pathway. SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-κB signaling pathway.

7 Alcohol Use Acuity and Burn Mortality: A Ten-Year Retrospective Analysis

Abstract Introduction The high incidence of alcohol consumption nationally is linked to increased susceptibility for burn injuries in both cases of acute intoxication as well as chronic misuse. While detection of elevated blood ETOH levels on admission intuitively does not always reflect a patient’s history of use, it does introduce bias and can influence clinical decision-making. Understanding these inherent biases at play, our institution through a retrospective analysis, sought to investigate the differing effects a positive blood alcohol level and true chronic alcohol use disorder had on overall mortality within our burn center. Methods We conducted a retrospective analysis utilizing data from the Institutional Burn Center Registry, which was linked to clinical and administrative records. Our study included all adult patients admitted to the Burn Center between January 1, 2012, and December 31, 2022. We collected and analyzed various parameters, including patient demographics, length of hospital stay (LOS), comorbid conditions, and mortality outcomes. Using logistic regression modeling we evaluated the association between burn mortality and ETOH. Results Over the ten-year study period, a total of 9,955 adult patients were admitted to our burn center. 6,943 tested negative and 541 patients tested positive for blood ETOH on admission. The remaining 2,471 had no test. 567 were determined to have a diagnosis of alcohol use disorder. A positive for ETOH did not have significant impact on mortality (p=0.76) while history of chronic ETOH use had a nearly three-fold increase in odds of mortality (OR 2.58, CI 1.52-4.24, p=0.000) when accounting for factors present in traditional predictive models such as burn size, age, and inhalational injury. Conclusions Chronic alcoholism has a greater association with mortality than acute alcohol intoxication at our institution. Further, clinicians should exercise caution when presuming alcohol use disorder solely based on a positive test. This highlights the necessity of accurate medical history taking when estimating and counseling patients on mortality risk. Applicability of Research to Practice This emphasizes the pressing need for research into the effects of multiple comorbidities and social determinants on mortality among burn patients. The insights gained have practical implications for refining clinical approaches and optimizing care strategies for this vulnerable patient population.

Boswellia dalzielii Methanol Stem Bark Extract Demonstrates Significant Analgesic Activity in Swiss Albino Mice

Medicinal plants are gaining popularity as safer and more natural alternatives to orthodox medicines for managing health challenges and diseases. One such plant is Boswellia dalzielii, a renowned tree in northern Nigeria extensively used due to its ethnomedicinal importance. To determine the analgesic properties of Boswellia dalzielii methanol extract (BDME), the extract was screened in mice using thermal and acetic acid-induced pain models. The extract's acute toxicity and phytochemical constituents were determined using standard protocols. The results showed that the acute toxicity of the methanol stem bark extract was greater than 2000 mg/kg. Phytochemical screening of BDME revealed the presence of flavonoids, tannins, saponins, and glycosides. The extract, at the dose of 50 mg/kg significantly (p &amp;lt; 0.05) prolonged the pain reaction time at 15 and 30 minutes in the hot plate test, and reduced acetic acid-induced writhing at the 12.5, 25, and 50 mg/kg doses. The analgesic activity of the extract may be attributed to the phytochemical contents. The findings suggest that BDME have analgesic properties and could be beneficial in alleviating painful conditions.