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1.
J Environ Sci (China) ; 147: 217-229, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39003041

ABSTRACT

Dissolved black carbon (DBC) plays a crucial role in the migration and bioavailability of iron in water. However, the properties of DBC releasing under diverse pyrolysis conditions and dissolving processes have not been systematically studied. Here, the compositions of DBC released from biochar through redox processes dominated by bacteria and light were thoroughly studied. It was found that the DBC released from straw biochar possess more oxygen-containing functional groups and aromatic substances. The content of phenolic and carboxylic groups in DBC was increased under influence of microorganisms and light, respectively. The concentration of phenolic hydroxyl groups increased from 10.0∼57.5 mmol/gC to 6.6 ∼65.2 mmol/gC, and the concentration of carboxyl groups increased from 49.7∼97.5 mmol/gC to 62.1 ∼113.3 mmol/gC. Then the impacts of DBC on pyrite dissolution and microalgae growth were also investigated. The complexing Fe3+ was proved to play a predominant role in the dissolution of ferrous mineral in DBC solution. Due to complexing between iron ion and DBC, the amount of dissolved Fe in aquatic water may rise as a result of elevated number of aromatic components with oxygen containing groups and low molecular weight generated under light conditions. Fe-DBC complexations in solution significantly promoted microalga growth, which might be attributed to the stimulating effect of dissolved Fe on the chlorophyll synthesis. The results of study will deepen our understanding of the behavior and ultimate destiny of DBC released into an iron-rich environment under redox conditions.


Subject(s)
Carbon , Charcoal , Iron , Oxidation-Reduction , Iron/chemistry , Charcoal/chemistry , Carbon/chemistry , Water Pollutants, Chemical/chemistry
2.
J Environ Sci (China) ; 147: 451-461, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39003061

ABSTRACT

Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.


Subject(s)
Ketoprofen , Ozone , Water Pollutants, Chemical , Ketoprofen/chemistry , Ozone/chemistry , Water Pollutants, Chemical/chemistry , Kinetics , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Models, Chemical , Water Purification/methods
3.
J Environ Sci (China) ; 149: 444-455, 2025 Mar.
Article in English | MEDLINE | ID: mdl-39181656

ABSTRACT

Oxidation of organic amines (OAs) or aromatic hydrocarbons (AHs) produces carbonyls, which further react with OAs to form carbonyl-amine condensation products, threatening environmental quality and human health. However, there is still a lack of systematic understanding of the carbonyl-amine condensation reaction processes of OAs or between OAs and AHs, and subsequent environmental health impact. This work systematically investigated the carbonyl-amine condensation coupled ozonolysis kinetics, reaction mechanism, secondary organic aerosol (SOA) formation and cytotoxicity from the mixture of dipropylamine (DPA) and styrene (STY) by a combined method of product mass spectrometry identification, particle property analysis and cell exposure evaluation. The results from ozonolysis of DPA and STY mixture revealed that STY inhibited the ozonolysis of DPA to different degrees to accelerate its own decay rate. The barycenter of carbonyl-amine condensation reactions was shifted from inside of DPA to between DPA and STY, which accelerated STY ozonolysis, but slowed down DPA ozonolysis. For the first time, ozonolysis of DPA and STY mixture to complex carbonyl-amine condensation products through the reactions of DPA with its carbonyl products, DPA with STY's carbonyl products and DPA's bond breakage product with STY's carbonyl products was confirmed. These condensation products significantly contributed to the formation and growth of SOA. The SOA containing particulate carbonyl-amine condensation products showed definite cytotoxicity. These findings are helpful to deeply and comprehensively understand the transformation, fate and environmental health effects of mixed organics in atmospheric environment.


Subject(s)
Aerosols , Air Pollutants , Amines , Ozone , Styrene , Ozone/chemistry , Amines/chemistry , Amines/toxicity , Kinetics , Styrene/chemistry , Styrene/toxicity , Air Pollutants/chemistry , Air Pollutants/toxicity , Humans , Oxidation-Reduction , Models, Chemical
4.
J Ethnopharmacol ; 336: 118705, 2025 Jan 10.
Article in English | MEDLINE | ID: mdl-39181288

ABSTRACT

ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.


Subject(s)
Arecaceae , Toxicity Tests, Acute , Animals , Female , Male , Arecaceae/chemistry , Mice , Plant Extracts/toxicity , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Immunologic Factors/toxicity , Rats , Toxicity Tests, Subacute , Dose-Response Relationship, Drug , Micronucleus Tests , Mutagenicity Tests , Hemolysin Proteins/toxicity , Lethal Dose 50
6.
Pest Manag Sci ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39229825

ABSTRACT

BACKGROUND: Sclerotinia sclerotiorum, a pathogenic fungus of oilseed rape, poses a severe threat to the oilseed rapeseed industry. In this study, we evaluated the potential of the natural compound hinokitiol against S. sclerotiorum by determining its biological activity and physiological characteristics. RESULTS: Our results showed that hinokitiol strongly inhibited the hyphae expansion of S. sclerotiorum, and its effective concentration of hyphae growing inhibition by 50% (EC50) against 103 S. sclerotiorum strains varied from 0.36 to 3.45 µg/mL, with an average of 1.23 µg/mL. Hinokitiol possessed better protective efficacy than therapeutic effects, and it exhibited no cross-resistance between carbendazim. After treatment with hinokitiol, many vesicular protrusions developed on the mycelium with rough surface and thickened cell wall. Moreover, the cell membrane permeability and glycerol content increased, while the oxalic acid declined after hinokitiol treatment. In addition, hinokitiol induced membrane lipid peroxidation and improved the production of reactive oxygen species (ROS) in S. sclerotiorum. Importantly, real-time quantitative polymerase chain reaction showed that cell wall and ROS synthesis-related genes were significantly up-regulated after hinokitiol treatment. CONCLUSION: This study revealed that hinokitiol has good biological activity against S. sclerotiorum and could be considered as an alternative bio-fungicide for the resistance management in controlling sclerotinia stem rot infected by S. sclerotiorum. These investigations provided new insights into understanding the toxic action of hinokitiol against pathogenic fungi. © 2024 Society of Chemical Industry.

7.
SAR QSAR Environ Res ; 35(7): 611-640, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39229871

ABSTRACT

The widespread use of pyrethroid and organophosphate pesticides necessitates accurate toxicity predictions for regulatory compliance. In this study QSAR and SSD models for six pyrethroid and four organophosphate compounds using QSAR Toolbox and SSD Toolbox have been developed. The QSAR models, described by the formula 48 h-EC50 or 96 h-LC50 = x + y * log Kow, were validated for predicting 48 h-EC50 values for acute Daphnia toxicity and 96 h-LC50 values for acute fish toxicity, meeting criteria of n ≥10, r2 ≥0.7, and Q2 >0.5. Predicted 48 h-EC50 values for pyrethroids ranged from 3.95 × 10-5 mg/L (permethrin) to 8.21 × 10-3 mg/L (fenpropathrin), and 96 h-LC50 values from 3.89 × 10-5 mg/L (permethrin) to 1.68 × 10-2 mg/L (metofluthrin). For organophosphates, 48 h-EC50 values ranged from 2.00 × 10-5 mg/L (carbophenothion) to 3.76 × 10-2 mg/L (crufomate) and 96 h-LC50 values from 3.81 × 10-3 mg/L (carbophenothion) to 12.3 mg/L (crufomate). These values show a good agreement with experimental data, though some, like Carbophenothion, overestimated toxicity. HC05 values, indicating hazardous concentrations for 5% of species, range from 0.029 to 0.061 µg/L for pyrethroids and 0.030 to 0.072 µg/L for organophosphates. These values aid in establishing environmental quality standards (EQS). Compared to existing EQS, HC05 values for pyrethroids were less conservative, while those for organophosphates were comparable.


Subject(s)
Daphnia , Pesticides , Pyrethrins , Quantitative Structure-Activity Relationship , Water Pollutants, Chemical , Pyrethrins/toxicity , Pyrethrins/chemistry , Animals , Daphnia/drug effects , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/chemistry , Pesticides/toxicity , Pesticides/chemistry , Organophosphates/toxicity , Organophosphates/chemistry , Fishes , Lethal Dose 50 , Insecticides/toxicity , Insecticides/chemistry
8.
J Biochem Mol Toxicol ; 38(9): e23837, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39230010

ABSTRACT

Synthesis of novel unnatural amino acids (UAAs) from 4-oxo-4-phenylbut-2-enoic acid derivatives with intramolecular aza-Michael addition reaction in the presence of chlorosulfonyl isocyanate (CSI) was reported in soft conditions without any metal catalyst. Acids and base as a catalyst, and solvents effects were investigated for the synthesis of novel UAAs. This novel method provides inexpensive, practicable, and efficient approach to generate UAAs. The use of UAAs has attracted great interest in the development of therapeutic agents and drug discovery to improve their properties. In this context, in addition to the synthesis of new UAAs, their inhibition effects on important metabolic enzymes of acetylcholinesterase (AChE) and carbonic anhydrases I and II (hCA I and II) enzymes were investigated. The compound 2g showed the best inhibition for CA I and AChE enzymes, while compound 2i exhibited the best inhibition profile against CA II isoenzyme. The inhibition values of these compounds were found as 1.85 ± 0.64 for AChE, 0.53 ± 0.07 for hCA I, 0.44 ± 0.15 µM for hCA II, respectively, and they showed a stronger inhibitory property than acetazolamide (standard inhibitor for hCA I and II) and tacrine (standard inhibitor for AChE) molecules. The activity of the studied molecule against different proteins that are hCA I (PDB ID: 2CAB), hCA II (PDB ID: 5AML), and AChE (PDB ID: 1OCE) was examined. Finally, the drug properties of the studied molecule were examined by performing absorption, distribution, metabolism, excretion, and toxicity analysis.


Subject(s)
Acetylcholinesterase , Amino Acids , Carbonic Anhydrase II , Carbonic Anhydrase I , Carbonic Anhydrase Inhibitors , Cholinesterase Inhibitors , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase I/antagonists & inhibitors , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Amino Acids/chemistry , Amino Acids/chemical synthesis , Carbonic Anhydrase II/antagonists & inhibitors , Humans , Carrier Proteins , Nerve Tissue Proteins , GPI-Linked Proteins
9.
Article in English | MEDLINE | ID: mdl-39230813

ABSTRACT

In recent years, heavy rainfall disasters linked to climate change have become more frequent, raising concerns about the release of chemicals stored in factories. Assessing chemical contamination during such emergencies therefore necessitates the development of a quick and easy method for evaluating hazardous contaminants in combination with toxicity testing. This study proposes a "toxicity screening" method that combines biological response testing and chemical analysis to systematically evaluate hazardous contaminants in emergency situations. The toxicity screening method evaluates the water quality in three steps, including water quality measurements and a delayed fluorescence (DF) assay, metal content measurements and a DF assay, and targeted screening analysis and a DF assay. The efficacy of this method was tested using industrial wastewater from 14 locations. Seven of the samples were non-toxic, while the other seven samples were toxic, displaying no observed effect concentration (NOEC) values ranging from 0.625 to 20%. Two toxic samples in the first phase possessed high total chlorine concentrations (0.4 mg L-1) and conductivities (2200 mS m-1), indicating that the main sources of toxicity were residual chlorine and a high salt concentration. In the second phase, metal content analysis identified metals as the toxicity cause in four samples. In the third phase, the organic contaminants were analyzed, and tri-n-octyl phosphate (TNOP) was detected at a concentration of 0.00027 mg L-1. The results of solid-phase extraction experiments and exposure tests with TNOP alone indicated that the contribution of TNOP to the toxicity was negligible and that chemicals not adsorbed on the solid-phase extraction cartridges were the cause of toxicity. The proposed method can therefore be considered effective for disaster-related water quality assessment, delivering results within 12 days.

10.
Clin Case Rep ; 12(9): e9376, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39219774

ABSTRACT

Stone heart syndrome has a complex interaction with digoxin toxicity, where, theoretically, the administration of intravenous calcium can worsen a patient's condition. Research on this subject is conflicting, so it is imperative to approach it cautiously.

11.
Clin Case Rep ; 12(9): e9371, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39219784

ABSTRACT

Clinical suspicion, clinical presentation, and electrocardiogram can help clinicians diagnose flecainide toxicity. Currently, there are no guidelines for the management of patients with flecainide toxicity. Sodium bicarbonate, lipid emulsion therapy, and extracorporeal life support have been used in this setting. Amiodarone and lidocaine can be used for the management of wide QRS complex tachycardias in hemodynamically stable patients with flecainide toxicity.

12.
Cureus ; 16(7): e65884, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39219880

ABSTRACT

We report a case comparing the measured half-life of flecainide with the half-life stated on the label. An 84-year-old woman presented with symptoms of anorexia and exertional dyspnea. She had undergone mitral and aortic valve replacements and excision of the membranous septum in the atrium for mitral and aortic stenosis and cor triatriatum. She was regularly administered 100 mg/day flecainide for paroxysmal atrial fibrillation. A previous electrocardiogram (ECG) showed a regular sinus rhythm. However, upon admission, the ECG revealed a heart rate of 94 bpm and an accelerated idioventricular rhythm originating from the left ventricle. Flecainide toxicity was suspected, leading to the discontinuation of flecainide treatment. The following day, the serum flecainide concentration was 1,348 ng/mL, exceeding the therapeutic window of 200-1,000 ng/mL. After discontinuing flecainide, the accelerated idioventricular rhythm ceased, and a regular sinus rhythm temporarily returned. We measured blood drug concentrations several times; our calculated half-life was 56.8 h, approximately five times longer than the half-life of 11.0 h stated on the package insert. To ensure safe and effective therapy with antiarrhythmic drugs, prioritizing therapeutic drug monitoring and carefully monitoring pharmacokinetics is important, particularly during the elimination phase.

13.
J Immunother Precis Oncol ; 7(3): 159-167, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39219992

ABSTRACT

In targeted therapies and immunotherapies, the occurrence of low-grade (e.g., grade 1-2) toxicities (LGT) is common, while dose-limiting toxicities (DLT) are relatively rare. As a result, conventional phase I trial designs, solely based on DLTs and disregarding milder toxicities, are problematic when evaluating these novel therapies. Methods: To address this issue, we propose a novel phase I design called a multiple-constraint keyboard (MC-Keyboard) that integrates multiple toxicity constraints, accounting for both DLT and LGT, for precise dose escalation and de-escalation, and identification of the maximum tolerated dose (MTD). As a model-assisted design, an important feature of MC-Keyboard is that its dose-escalation or de-escalation rule can be pretabulated and incorporated into the trial protocol before the initiation of the trial, greatly simplifying its implementation. Results: The simulation study showed that the MC-Keyboard had high accuracy in identifying the MTD and is safer than some existing designs. Conclusion: The MC-Keyboard provides a novel, simple, and safe approach to assessing safety and identifying the MTD for targeted therapies and immunotherapies.

14.
Front Microbiol ; 15: 1444374, 2024.
Article in English | MEDLINE | ID: mdl-39220045

ABSTRACT

The pollution of heavy metals (HMs) is a major environmental concern for agricultural farming communities due to water scarcity, which forces farmers to use wastewater for irrigation purposes in Pakistan. Vegetables grown around the cities are irrigated with domestic and industrial wastewater from areas near mining, paint, and ceramic industries that pollute edible parts of crops with various HMs. Cadmium (Cd) is an extremely toxic metal in arable soil that enters the food chain and damages the native biota, ultimately causing a reduction in plant growth and development. However, the use of microbes and growth regulators enhances plant growth and development as well as HM immobilization into the cell wall and hinders their entry into the food chain. Thus, the integrated use of bacterial consortium along with exogenously applied jasmonic acid (JA) mitigates the adverse effect of metal stress, ultimately reducing the metal mobility into roots by soil. Therefore, the current study was conducted to check the impact of Cd-tolerant bacteria and JA on the growth, nutrient status, and uptake of Cd in the cauliflower (Brassica oleracea). Our results demonstrated that increasing concentrations of Cd negatively affect growth, physiological, and biochemical attributes, while the use of a bacterial consortium (SS7 + SS8) with JA (40 µmol L-1) significantly improved chlorophyll contents, stem fresh and dry biomass (19.7, 12.7, and 17.3%), root length and root fresh and dry weights (28.8, 15.2, and 23.0%), and curd fresh and dry weights and curd diameter (18.7, 12.6, and 15.1%). However, the maximum reduction in soil Cd, roots, and curd uptake was observed by 8, 11, and 9.3%, respectively, under integrated treatment as compared to the control. Moreover, integrating bacterial consortium and JA improves superoxide dismutase (SOD) (16.79%), peroxidase dismutase (POD) (26.96%), peroxidase (POX) (26.13%), and catalase (CAT) (26.86%). The plant nitrogen, phosphorus, and potassium contents were significantly increased in soil, roots, and curd up to 8, 11, and 9.3%, respectively. Hence, a consortium of Klebsiella strains in combination with JA is a potential phytostabilizer and it reduces the uptake of Cd from soil to roots to alleviate the adverse impact on cauliflower's growth and productivity.

15.
Asia Pac J Oncol Nurs ; 11(9): 100552, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39220148

ABSTRACT

Objective: The aim of this study was to assess the level of financial toxicity (FT) experienced by the following three age groups of cancer patients in China: young working-aged patients (age < 40 years), middle-aged patients (40-64 years), and older patients (≥ 65 years). Methods: The data used for this study were collected via a cross-sectional survey conducted in China. FT was assessed using the Comprehensive Score for Financial Toxicity (COST). ANOVA was used to examine the differences in FT status between age groups. Multivariate linear regression models were employed to assess the association between age and FT, adjusted by socioeconomic and other clinical characteristics. Results: A total of 556 cancer patients completed the survey. Approximately 54.3% of the participants were male and 45.7% were female. The majority (61.5%) were aged 40-64 years, while 27.7% were aged 65 or older. The mean FT scores for young patients (< 40 years), middle-aged patients (40-64 years), and older patients (≥ 65 years) were 16.7, 12.8, and 12.4, respectively. The results of the regression analysis revealed that, without adjusting for background characteristics, young patients had significantly higher mean COST scores. This suggests they experienced lower levels of FT compared to patients in other age groups. Stratified analysis revealed that, for older patients, only educational level and type of insurance scheme were significant factors in predicting the COST score. Conclusions: This study provides empirical evidence for developing targeted interventions and policies to reduce the FT for patients in different age groups. Given that FT is complicated, a longitudinal study should be conducted to explore the long-term impact of FT on cancer patients' quality of life and well-being.

16.
Front Pediatr ; 12: 1424919, 2024.
Article in English | MEDLINE | ID: mdl-39220154

ABSTRACT

We describe the case of a 14-year-old girl with osteosarcoma who was treated with high-dose methotrexate (12 g/m2). Twenty-four hours after the infusion, her plasma methotrexate concentration was elevated at 937 µmol/L (normal < 10 µmol/L). She exhibited severe signs of methotrexate toxicity, including encephalopathy, acute liver failure (ALF), and acute kidney injury. In this case report, we highlight the severe and rare adverse effects secondary to methotrexate administration and the efficacity of molecular adsorbent recirculating system and continuous venovenous hemodiafiltration to recover from multiple organ failure.

17.
F1000Res ; 13: 260, 2024.
Article in English | MEDLINE | ID: mdl-39220381

ABSTRACT

Introduction: Poweromin X Ten (PXT) is a polyherbal formulation, traditionally used to enhance male sexual function. However, the safety and benefits of PXT have not been scientifically evaluated. Therefore, the present study investigated the toxicity and aphrodisiac potential of PXT in male rats and explored its principal mechanisms of action. Methods: Male Wistar rats were orally administered PXT (50 or 100 mg/kg) for 28 days, and sexual activity parameters, including latency and frequency of mounting and intromissions, were studied. The reproductive toxicity and spermatogenic potential were also examined. Furthermore, dopamine and serotonin levels in brain regions associated with sexual activity were assessed. Network analysis was used to identify the key bioactive compounds and their core targets involved in their beneficial actions. Results: Treatment with PXT improved sexual activity in male rats, as evidenced by reduced mounting and intromission latency and a significant increase in mount frequency. Moreover, PXT exhibited spermatogenic potential and did not induce reproductive toxicity. Notably, treatment with 50 mg/kg PXT elevated dopamine levels in median preoptic area and hypothalamus. Pathway analysis indicated that PXT primarily modulated the PI3K-Akt, calcium, and MAPK signalling pathways to enhance male sexual function. Network analysis identified macelignan, ß-estradiol, testosterone, and paniculatine as key bioactive components of PXT, which likely act through core targets, such as androgen receptor (AR), Mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), and vascular endothelial growth factor (VEGF) to facilitate the improvement of male sexual function. Conclusion: Study results suggest that PXT is a safer alternative with aphrodisiac and spermatogenic potential. These effects are partly attributed to the enhanced dopamine levels in the brain. Furthermore, this study provides insights into the specific signalling pathways and bioactive compounds that underlie the improvements in male sexual function associated with PXT.


Subject(s)
Dopamine , Rats, Wistar , Sexual Behavior, Animal , Animals , Male , Sexual Behavior, Animal/drug effects , Rats , Dopamine/metabolism , Network Pharmacology , Plant Extracts/pharmacology , Serotonin/metabolism , Aphrodisiacs/pharmacology
18.
Front Psychol ; 15: 1410620, 2024.
Article in English | MEDLINE | ID: mdl-39220400

ABSTRACT

More than half of all game players report experiencing some form of hate, harassment or abuse within gaming spaces. While prevalence assessments of these actions in digital gaming spaces are ongoing, little remains known about the more extreme forms of these behaviors. Specifically, experiences of extremism. This paper addresses the gap in research knowledge around the expression of extremist sentiment in games by evaluating their prevalence, location, and nature, and impact. Assessing experiences via an online survey, game players (n = 423) reported an alarmingly high rate of frequency for being the direct target of, as well as a witness to, all forms of extremist content. Most of these experiences were text-based, reported to be happening in-game. Most players endorsed statements relating to a normalization of extreme ideologies within gaming cultures. It is promising that reporting these behaviors was the primary action taken by players for most of the players; however, "ignoring" these actions was also a common strategy. It is possible that player inaction reflects the embeddedness and normalization of these actions in gaming spaces and/or a lack of trust in moderation systems to be responsive. The prevalence of extreme sentiment in gaming cultures should raise concern from game makers, members of the gaming community, parents, and policy makers alike.

19.
Environ Sci Ecotechnol ; 22: 100471, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39220680

ABSTRACT

Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats' reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor ß1 (TGF-ß1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-ß1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

20.
Cancer Manag Res ; 16: 1077-1090, 2024.
Article in English | MEDLINE | ID: mdl-39220814

ABSTRACT

Purpose: The purpose of this study is to understand the level of quality of life (QOL) of lung cancer patients receiving immunotherapy and to clarify the potential mediating role of self-perceived burden (SPB) in the relationship between financial toxicity (FT) and QOL. Patients and Methods: A convenience sample of 342 lung cancer patients receiving immunotherapy was recruited from a cancer hospital from October 2022 to April 2023 for this cross-sectional study. The participants were requested to complete the following structured questionnaires: a sociodemographic and clinical questionnaire, the Functional Assessment of Cancer Therapy-Lung (FACT-L), the Self-Perceived Burden Scale (SPBS) and the COmprehensive Score for Financial Toxicity (COST). The data were subjected to Pearson correlation analysis and bootstrapping analysis in structural equation modelling. Results: The total FACT-L score was 79.90±15.84 points in 322 lung cancer patients receiving immunotherapy. FT (ß = 0.37, P < 0.01) and SPB (ß = -0.27, P < 0.01) had a direct effect on QOL. In addition, SPB partly mediated the association between FT and QOL, and the standardized indirect effect was 0.19, accounting for 33.9% of the total effect. Conclusion: The present study revealed that there is still much room for improvement in the QOL of lung cancer patients during immunotherapy. A greater financial burden resulted in a greater self-perceived burden and was thus associated with inferior QOL. It is imperative for oncology nurses to routinely assess QOL, FT or risk and SPB for lung cancer patients undergoing immunotherapy as well as to assist those patients in understanding the potential financial risk of each choice and help them take more active roles in their routine clinical care.

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