ToxiconPub Date : 2024-09-18DOI: 10.1016/j.toxicon.2024.108104
Stefano Maffè, Paola Paffoni, Emanuela Facchini, Luca Bergamasco, Eleonora Prenna, Sara Ariotti, Anna Maria Paino, Stefano Ticozzi, Chiara Anchisi, Pierfranco Dellavesa
{"title":"Venom-induced myocarditis: An unusual case attributable to Vipera aspis bite","authors":"Stefano Maffè, Paola Paffoni, Emanuela Facchini, Luca Bergamasco, Eleonora Prenna, Sara Ariotti, Anna Maria Paino, Stefano Ticozzi, Chiara Anchisi, Pierfranco Dellavesa","doi":"10.1016/j.toxicon.2024.108104","DOIUrl":"10.1016/j.toxicon.2024.108104","url":null,"abstract":"<div><p>Venomous bites are medical emergencies that may result in life-threatening clinical effects. Cardiovascular complications are uncommon but they can be dangerous if not early detected and treated. Cerebral and myocardial infarction are described; myocarditis as consequence of viper envenomation in humans are very rare, almost anedoctal. We present the case of a 33-year-old man, working as keeper in a reptile zoo, who arrived after a viper bite of the <em>Vipera aspis</em> species, on the left wrist. The patient presented with clouded sensorium, edema of the lips and tongue, rapidly worsened with angioedema, and the need for oro-tracheal intubation; severe thrombocytopenia and anemia were treated with transfusions of platelet, plasma and red blood cells. The left hand and arm worsened, with compartment syndrome, treated with surgical fasciotomy<u>.</u> From a cardiological point of view, the patient presented a sudden drop in blood pressure, electrocardiographic anterior and infero-lateral ST depression, pericardial effusion and hypokinesia of the interventricular septum on echocardiography, and a significant increase in troponin T. Cardiac magnetic resonance imaging confirmed the myocarditis, with the presence of septal and anterior intramyocardial edema in T2 weighted sequences, with prolonged T2 time at T2 mapping analysis, without late gadolinium enhancement areas. Cardiological and general clinical conditions gradually improved only after the antivenom was administred. This is one of the rare cases of viper bite myocarditis with echocardiographic and magnetic resonance imaging documentation in Europe; it emphasizes the importance of identifying uncommon complications of venomous snake-bites and the prompt administration of antivenom, even though snake bites are less frequent at our latitudes.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-17DOI: 10.1016/j.toxicon.2024.108100
Bruno Oliveira Almeida, Eduardo Silva Reis Barreto, Cesar Romero Antunes Júnior, Vinicius Borges Alencar, Anna Karla do Nascimento Souza, Liana Maria Torres de Araujo Azi, Liliane Elze Falcão Lins-Kusterer, Durval Campos Kraychete
{"title":"Evaluating the efficacy of botulinum toxin in treating complex regional pain syndrome: A systematic review","authors":"Bruno Oliveira Almeida, Eduardo Silva Reis Barreto, Cesar Romero Antunes Júnior, Vinicius Borges Alencar, Anna Karla do Nascimento Souza, Liana Maria Torres de Araujo Azi, Liliane Elze Falcão Lins-Kusterer, Durval Campos Kraychete","doi":"10.1016/j.toxicon.2024.108100","DOIUrl":"10.1016/j.toxicon.2024.108100","url":null,"abstract":"<div><div>Complex Regional Pain Syndrome (CRPS) is characterized by pain, swelling, limited range of motion, skin changes, vasomotor instability, and bone demineralization. This study aims to assess the efficacy of botulinum toxin type A (BoNT-A) in the treatment of CRPS. We conducted a systematic literature review following the PRISMA guidelines, using the PICO strategy (Patient, Intervention, Comparison and Outcome) with the following criteria: P = Patients with CRPS; I = Botulinum toxin; C = Placebo or active drug; and O = Pain relief. Three randomized controlled trials with placebo controls were included, involving a total of 64 patients, 36 of whom received BoNT-A in doses ranging from 40U to 200U. The studies examined both lumbar sympathetic block and local application methods. Botulinum toxin shows promise in alleviating pain associated with CRPS, particularly when used as an adjunct to lumbar sympathetic blockade. However, the limited number of studies and small sample sizes impede reaching definitive conclusions regarding its efficacy and safety. Notably, local applications (intradermal or subcutaneous) require further investigation, as current evidence is insufficient and reports indicate patient discomfort. While preliminary findings suggest potential benefits of BoNT-A in managing CRPS, larger randomized trials are necessary to confirm its efficacy and safety.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-14DOI: 10.1016/j.toxicon.2024.108098
Diaa Attia Marrez , Ahmed Noah Badr , Amanallah El-Bahrawy , Mohamed Ahmed Naeem
{"title":"Algal extracts evaluation as an Antitoxicity sustainable solution against aflatoxin B1 toxicity in rat tissues","authors":"Diaa Attia Marrez , Ahmed Noah Badr , Amanallah El-Bahrawy , Mohamed Ahmed Naeem","doi":"10.1016/j.toxicon.2024.108098","DOIUrl":"10.1016/j.toxicon.2024.108098","url":null,"abstract":"<div><p>Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) is a pre-carcinogenic molecule produced by toxigenic fungi and is widely harmful to public health. Algae extracts are sub-cellular pilot plants rich in bioactive substances that aid detoxification. This study aimed to reduce AFB<sub>1</sub>-toxicity in biological tissues of administrated rats using two algae extracts, <em>Spirulina</em> (SPR) and <em>Amphora</em> (AMR). Algae extracts were prepared using an aqueous system, concentrated, and lyophilized before being administrated to rats. The extract contents of total phenolic and flavonoids were determined to indicate their bioactive content and antioxidant potency. The animal experiment was designed in 8 groups as the control negative and control positive (AFB<sub>1</sub>; 20 μg/kg BW/day); groups 3 and 4 were designed for control positive of algae applied at high doses for toxicity evaluation. Otherwise, four groups were classified as G5 and G6 for rats administrated by AFB<sub>1,</sub> followed by 50 and 100 mg/kg <em>Spirulina</em> extract, respectively. The G7 and G8 were administrated with an AFB1 dose followed by amphora treatment at 50 and 100 mg extract/kg, respectively. The results showed a significant content of algae extracts of phenolic compounds (27.36 ± 1.75 and 39.55 ± 1.14 mg GAE/g DW for the SPR and AMR, respectively), with a valuable antioxidant activity. For rats treated only with the SPR or AMR extracts, no tissue changes were recorded for the liver, kidney, pancreas, or testis. Again, the biochemical parameters of these groups are recorded without harmful impacts, particularly for the tumor markers of AFP, TNF-α, CEA, and ALP. Once more, a higher extract concentration was more effective in AFB<sub>1</sub>-toxicity reduction, particularly for the SPR on the liver and kidney tissues. The SPR extract manifested a protective impact in sensitive tissue against the AFB<sub>1</sub> effect, particularly in the testis. The results recommend the application of SPR extract at 100 mg/kg bw as an effective treatment for AFB<sub>1</sub>-toxicity regulation (as pharmaceutical or nutraceutical) involved in daily habits.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-13DOI: 10.1016/j.toxicon.2024.108103
Vildan Betul Yenigun , Abdurrahim Kocyigit , Ebru Kanimdan , Ezgi Balkan , Ayse Zehra Gul
{"title":"Copper (II) increases anti-Proliferative activity of thymoquinone in colon cancer cells by increasing genotoxic, apoptotic, and reactive oxygen species generating effects","authors":"Vildan Betul Yenigun , Abdurrahim Kocyigit , Ebru Kanimdan , Ezgi Balkan , Ayse Zehra Gul","doi":"10.1016/j.toxicon.2024.108103","DOIUrl":"10.1016/j.toxicon.2024.108103","url":null,"abstract":"<div><p>Thymoquinone is the main active compound derived from the essential oil of the <em>Nigella sativa</em> plant seed. While thymoquinone is an antioxidant, it has been reported in several studies that thymoquinone has dose-dependent pro-oxidant activity with the Fenton reaction in the presence of transition elements such as iron and copper. This study aimed to investigate cytotoxic, apoptotic, genotoxic, and reactive oxygen species (ROS) generating effects of thymoquinone treated with copper in colon cancer cells. HT-29 cells were treated with pro-oxidant-acting doses of thymoquinone alone and together with the non-toxic dose of Copper (II) Sulfate for 24 h. Cytotoxic, apoptotic, genotoxic, and ROS production activities were analyzed by MTT viability test, Acridine Orange/Ethidium Bromide (AO/EB) staining, alkaline single cell gel electrophoresis and H2DCF-DA assay, respectively. Viability results showed that thymoquinone and copper synergistically affect cancer cells, and DNA damage was increased with the synergic effect. The intracellular ROS was increased when thymoquinone and copper were applied together. Applying redox-active copper (II) with thymoquinone increases DNA damage, apoptosis, and cell death by increasing the amount of intracellular ROS through pro-oxidant activity. Treatments targeting copper-related pathways may open new therapeutic avenues for cancer treatment.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-12DOI: 10.1016/j.toxicon.2024.108102
Tooba Nauroze , Shaukat Ali , Shagufta Andleeb , Chaman Ara , Lubna Kanwal , Samaira Mumtaz , Muhammad Summer , Rizwan Ullah
{"title":"Quantitative assessment of Nigella sativa and conjugated silver nanoparticles against hexavalent chromium toxic effects on sperm function","authors":"Tooba Nauroze , Shaukat Ali , Shagufta Andleeb , Chaman Ara , Lubna Kanwal , Samaira Mumtaz , Muhammad Summer , Rizwan Ullah","doi":"10.1016/j.toxicon.2024.108102","DOIUrl":"10.1016/j.toxicon.2024.108102","url":null,"abstract":"<div><h3>Background</h3><p>Infertility has been observed as one of the major issues in humans, one known risk factor is heavy metals.</p></div><div><h3>Methods</h3><p>The main focus of the present research was to assess the toxic effect of hexavalent chromium (Cr (VI)) on sperm and its mitigation by <em>Nigella sativa</em> seed extract (NS) and its conjugated silver nanoparticles (NS + NP). In the present study, we administered 1.5 mg/kg body of Cr (VI) orally in mice for 60 days routinely, to induce toxicity in testes and effect on sperm production and motility in male mice. NS and NS + NP (50 mg/kg body weight) were administered to evaluate protective action against Cr (VI). The sperm were analyzed by computer-assisted semen analysis (CASA) and chromium concentration in testicular tissue was measured via the atomic absorption spectrophotometer.</p></div><div><h3>Results</h3><p>The CASA analysis showed that Cr (VI) was directly linked with a decline in sperm concentration, motility, distance, velocity, straightness, and head beat frequency attributes. However, the administration of <em>Nigella sativa</em> seed extract and its green synthesized silver nanoparticles improved sperm concentration, motility, distance, velocity, straightness, and head beat frequency. The chromium content in the testes of Cr-exposed animals significantly increased, which negatively affected sperm parameters. However, <em>Nigella sativa</em> and <em>Nigella sativa</em> conjugated silver nanoparticles appeared to help in the removal of Cr content from testes hence improving the sperm parameters in exposed mice.</p></div><div><h3>Conclusion</h3><p>The decrease in Cr concentration improved sperm quality and quantity, hence, improve male fertility.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-12DOI: 10.1016/j.toxicon.2024.108101
Deeikshana T , Poorniammal R , Shandeep S G , Vijay S , Prabhu S
{"title":"Exploring nematicidal biomolecules from Xenorhabdus nematophila as a novel source for Meloidogyne incognita management","authors":"Deeikshana T , Poorniammal R , Shandeep S G , Vijay S , Prabhu S","doi":"10.1016/j.toxicon.2024.108101","DOIUrl":"10.1016/j.toxicon.2024.108101","url":null,"abstract":"<div><p>Attempts were made to evaluate the purified bioactive compounds of <em>Xenorhabdus nematophila</em> against <em>Meloidogyne incognita</em>. In order to extract the purified compounds, a solid-supported liquid-liquid extraction system with a flow rate (1 mL/min) was used to purify bioactive molecules. Compounds were individually collected concentrated and evaluated against <em>M. incognita</em>. Among 25 fractions the L19 fraction, exhibited 98% inhibition in egg hatching and mortality of juveniles. The biomolecules were identified through Liquid Chromatography- Mass Spectroscopy (LC-MS) technique. To decipher the mode of action of compounds, molecular docking studies were performed with potential protein targets such as acetylcholinesterase, β-1,4-endoglucanase, glutathione S-transferase-1, cytochrome <em>c</em> oxidase, G-protein coupled receptor and Fatty acid and retinol-binding proteins of <em>M. incognita</em>. The results revealed that among eight compounds from the L19 fraction, malonate and pidopidon exhibited greater binding affinity towards the selected protein targets of <em>M. incognita</em>. <em>In vitro</em> studies with malonate and pidopidon against <em>M. incognita</em> showcased a 99% reduction in egg hatching and juvenile mortality. Moreover, greenhouse experiments revealed that malonate compounds not only reduced 94% of the <em>M. incognita</em> population but also enhanced the plant growth parameters in tomato by 60%. Hence the present study stands novel in exploiting the nematicidal compounds from <em>X. nematophila</em> giving limelight to explore pidopidon and malonate as novel nematicidal compounds for the management of <em>M. incognita.</em></p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-10DOI: 10.1016/j.toxicon.2024.108099
Kim Hoon Choo , Anisah binti Adnan , Ahmad Khaldun Ismail
{"title":"Multiple ventricular premature complexes following equatorial spitting cobra (Naja sumatrana) envenomation","authors":"Kim Hoon Choo , Anisah binti Adnan , Ahmad Khaldun Ismail","doi":"10.1016/j.toxicon.2024.108099","DOIUrl":"10.1016/j.toxicon.2024.108099","url":null,"abstract":"<div><p><em>Naja</em> species bite is the commonest cause for consultation to Remote Envenomation Consultancy Services in Malaysia. Envenomation by <em>Naja</em> species may result in neuroparalysis and cardiotoxic effects including arrhythmias, hypertension, tachycardia, atrioventricular blocks, ventricular tachycardia, and ventricular fibrillation. We report a case of cardiotoxicity as an early manifestation following an equatorial spitting cobra, <em>Naja sumatrana</em> bite, preceding early paralytic envenomation manifestation. A 14-year-old boy presented to an emergency department with mild local envenomation. ECG showed multiple ventricular premature complexes. Subsequently patient developed ptosis. Complete resolution of ptosis and resumption of normal sinus rhythm occurred following administration of the appropriate antivenom. The patient was discharged well after two days of hospitalization. The patient's ECG findings and neurotoxic manifestation suggested acute systemic envenomation. High index of suspicion for cardiotoxicity with close serial monitoring is recommended to ensure timely administration of antivenom.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-04DOI: 10.1016/j.toxicon.2024.108089
M.D. Dinesh , Thirunavukkarasu P , Thulasi Sivaraman , K.V. Anju , Thushara James , Dhanusha J. Nair
{"title":"Obscure properties of a traditional herb Pittosporum neelgherrense used to treat snakebite envenoming against Daboia russelli venoms","authors":"M.D. Dinesh , Thirunavukkarasu P , Thulasi Sivaraman , K.V. Anju , Thushara James , Dhanusha J. Nair","doi":"10.1016/j.toxicon.2024.108089","DOIUrl":"10.1016/j.toxicon.2024.108089","url":null,"abstract":"<div><p>In tropical nations, snakebite envenomation is a significant public health issue with negative human and social effects. This is due to three factors: 1) more species of the most hazardous snakes are present; 2) emergency medical assistance is not readily available; and 3) inadequate health care. The problems caused by snakebite envenomation have been partially resolved by immunotherapy. An extensive collection of medicinal herbs is recognized to have antivenomous properties in traditional medicine. However, very few species have undergone scientific investigation, and even fewer have had their active components separated and structurally and functionally defined. In this work, the anti-venom potential of hot and cold aqueous extracts from <em>Pittosporum neelgherrense</em> is evaluated using an in-vitro model. The experimental results showed that 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-(11.20), 1-Undecanol (16.38), Lauryl acetate (18.25), and Cyclotridecane (19.14) were phytochemical substances whose chemical structures were recognized by GCMS. The Direct and Indirect hemorrhagic activity was found to be completely neutralized by <em>P. neelgherrense</em> extract (44.61% hot plant extract & 55.38% cold plant extract) and the zone (2.4 mm), respectively. The neutralization of venoms was indicated by the zone (0.5–0.9 cm) of hydrolysis production of proteolytic activity. Additionally, the results of the gelatine liquefaction study demonstrated that clot formation was not triggered by venom at low concentrations (50:50) but was instead brought on by higher concentrations. The present study suggested that the neutralization of venom by hot water extracts of <em>P. neelgherrense</em> is a potentially therapeutic application.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structure-aided function assignment to the transcriptomic conopeptide Am931","authors":"Shamasoddin Shekh , Shweta Dhannura , Pooja Dhurjad , Challa Ravali , Spoorti M M , Sreepriya Kakkat , Vishwajyothi , Marimuthu Vijayasarathy , Rajesh Sonti , Konkallu Hanumae Gowd","doi":"10.1016/j.toxicon.2024.108087","DOIUrl":"10.1016/j.toxicon.2024.108087","url":null,"abstract":"<div><p>Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of <em>Conus</em> peptides. The proof of the concept was demonstrated using the transcriptomic peptide Am931 of <em>C. amadis</em>. The 3D structure of Am931 was computed using Density Functional Theory (DFT) and the quality of the predicted structure was confirmed using 2D NMR spectroscopy of the corresponding synthetic peptide. The computed structure of Am931 aligns with the active site motif of thioredoxins, possess catalytic disulfide conformation of (+, −)AntiRHHook and selectively modulate the N-terminal Cys3 thiol. These structural features indicate that Am931 may act as a disulfide isomerase and modulate the oxidative folding of conotoxins. Synthetic peptide Am931 provides proof-of-function by exhibiting catalytic activity on the oxidative folding of α-conotoxin ImI and improving the yield of native globular fold. The approach of integration of new technologies in the <em>Conus</em> peptide research may help to accelerate the discovery pipeline of new/improved conotoxin functional.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxiconPub Date : 2024-09-03DOI: 10.1016/j.toxicon.2024.108090
Zhengyan Gong , Xuemei Wang , Yuhong Li , Yixuan Nie , Yu Hu , Yanbin Chen , Xiujuan Peng , Feng Liu , Bingling Dai , Yanmin Zhang
{"title":"Yangzheng mixture reversed EMT against hepatocellular carcinoma metastasis via NF-κB/NLRP3/β-catenin pathway","authors":"Zhengyan Gong , Xuemei Wang , Yuhong Li , Yixuan Nie , Yu Hu , Yanbin Chen , Xiujuan Peng , Feng Liu , Bingling Dai , Yanmin Zhang","doi":"10.1016/j.toxicon.2024.108090","DOIUrl":"10.1016/j.toxicon.2024.108090","url":null,"abstract":"<div><p>Yangzheng mixture has been used as an adjuvant tumor therapy as a traditional Chinese medicine in clinical. However, less is known about the activity of Yangzheng mixture. In our study, we explored the anti-tumor activity of Yangzheng mixture for HCC <em>in vitro</em> and <em>in vivo</em>. The effects of Yangzheng mixture on HCC biological behaviors were assessed using colony formation assay, EdU staining, cell cycle assay, Annexin V/PI staining, and wound healing assay. Migration and invasion of HCC cells were further evaluated via transwell assays, while molecular mechanisms were investigated through western blotting and immunofluorescence staining. Additionally, the anticancer effect of Yangzheng mixture <em>in vivo</em> were examined using H22 xenograft and H22 metastatic hepatocellular carcinoma models. Our results revealed that Yangzheng mixture inhibited colony formation, EdU incorporation, cell migration, and invasion, while arresting cell cycle at the G2-M phase in Bel-7402 and SMMC-7721 cells. Mechanistic studies demonstrated that Yangzheng mixture showed a markedly inhibition on Bel-7402 and SMMC-7721 cells with higher NLRP3 expression. We further confirmed that Yangzheng mixture could activate NLRP3 inflammasome through NF-κB by western blotting and immunofluorescence staining. Additionally, Yangzheng mixture inhibited β-catenin nucleus translocation and reversed EMT process. <em>In vivo</em>, the H22 xenograft model depicted that Yangzheng mixture significantly reduced tumor size and weight compared with control. Moreover, H22 lung metastasis model showed that Yangzheng mixture significantly inhibited liver cancer cell spreading to lungs in mice. Overall, our finding revealed that Yangzheng mixture inhibited HCC proliferation and migration <em>in vitro</em> and <em>in vivo</em> by reversing EMT via NF-κB/NLRP3/β-catenin pathway. These results may serve new therapeutic evidences for Yangzheng mixture application in clinical.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}