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Yangzheng mixture reversed EMT against hepatocellular carcinoma metastasis via NF-κB/NLRP3/β-catenin pathway 养正混合物通过NF-κB/NLRP3/β-catenin通路逆转肝细胞癌转移的EMT作用
IF 2.6 4区 医学
Toxicon Pub Date : 2024-09-03 DOI: 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 ,&nbsp;Xuemei Wang ,&nbsp;Yuhong Li ,&nbsp;Yixuan Nie ,&nbsp;Yu Hu ,&nbsp;Yanbin Chen ,&nbsp;Xiujuan Peng ,&nbsp;Feng Liu ,&nbsp;Bingling Dai ,&nbsp;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":"250 ","pages":"Article 108090"},"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}
引用次数: 0
A retrospective observational study of mangrove pit viper envenomation presented to selangor middle zone cluster hospitals in Malaysia 对马来西亚雪兰莪州中区联网医院接诊的红树林蝮蛇感染病例的回顾性观察研究。
IF 2.6 4区 医学
Toxicon Pub Date : 2024-09-02 DOI: 10.1016/j.toxicon.2024.108086
Xin Yi Chan , Jasmine Anthonysamy , Ranjini Sivaganabalan , Choo Hock Tan , Ruth Sabrina Binti Safferi , Rafidah Abdul Rahim , Kim Hoon Choo , Ahmad Badrul Amin
{"title":"A retrospective observational study of mangrove pit viper envenomation presented to selangor middle zone cluster hospitals in Malaysia","authors":"Xin Yi Chan ,&nbsp;Jasmine Anthonysamy ,&nbsp;Ranjini Sivaganabalan ,&nbsp;Choo Hock Tan ,&nbsp;Ruth Sabrina Binti Safferi ,&nbsp;Rafidah Abdul Rahim ,&nbsp;Kim Hoon Choo ,&nbsp;Ahmad Badrul Amin","doi":"10.1016/j.toxicon.2024.108086","DOIUrl":"10.1016/j.toxicon.2024.108086","url":null,"abstract":"<div><h3>Objective</h3><p>There is very limited published experience on mangrove pit viper envenomation in the medical literature. This study aims to analyze the clinical characteristics, treatment modalities and outcomes of patients presenting to Selangor middle zone cluster Hospitals in Malaysia with confirmed mangrove pit viper bites.</p></div><div><h3>Methods</h3><p>We conducted a retrospective observational study, reviewing medical records of patients treated for mangrove pit viper bites between July 1, 2020 to June 30, 2023. Data on patient demographics, clinical characteristic, laboratory findings, treatment modalities and clinical outcomes were collected and analyzed.</p></div><div><h3>Results</h3><p>A total of 25 patients were included in this study. The majority of the patients were male (n = 23, 92%) with the mean age of 38.7 ± 17.6 years. Most frequent anatomical region involved is foot (n = 12, 48%). Common clinical presentation included localized pain (n = 24, 96%), swelling (n = 22, 88%) and fang mark (n = 22, 88%). Systemic symptoms were less common, with 1 patient exhibiting coagulopathy with clinical bleeding at 28 h post bite. Antivenom was administered to 68% (n = 17) of the patients. The majority of the patients (n = 23, 92%) recovered without significant morbidity while 8% (n = 2) of the patients developed skin infection that required antibiotic therapy. No fatalities were reported.</p></div><div><h3>Conclusion</h3><p>Mangrove pit viper envenomation encountered in these regions predominantly causes local symptoms while systemic symptoms were less common. This study provides a glimpse to the clinical characteristics and management of mangrove pit viper envenomation, coagulopathy may be delayed due to characteristic of the snake venom and patient's preexisting illness. Further research is needed to enhance our understanding of this snakebite envenomation.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"249 ","pages":"Article 108086"},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133864","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}
引用次数: 0
Effects of alfa lipoic acid and coenzyme Q10 treatment on AFB1-induced oxidative, inflammatory, and DNA damages in rats 阿法硫辛酸和辅酶 Q10 对 AFB1 诱导的大鼠氧化、炎症和 DNA 损伤的影响
IF 2.6 4区 医学
Toxicon Pub Date : 2024-09-01 DOI: 10.1016/j.toxicon.2024.108083
Ghadeer M. Albadrani , Ahmed E. Altyar , Osama A. Kensara , Mohie A.M. Haridy , Mohamed Sayed Zaazouee , Alaa Ahmed Elshanbary , Amany A. Sayed , Mohamed M. Abdel-Daim
{"title":"Effects of alfa lipoic acid and coenzyme Q10 treatment on AFB1-induced oxidative, inflammatory, and DNA damages in rats","authors":"Ghadeer M. Albadrani ,&nbsp;Ahmed E. Altyar ,&nbsp;Osama A. Kensara ,&nbsp;Mohie A.M. Haridy ,&nbsp;Mohamed Sayed Zaazouee ,&nbsp;Alaa Ahmed Elshanbary ,&nbsp;Amany A. Sayed ,&nbsp;Mohamed M. Abdel-Daim","doi":"10.1016/j.toxicon.2024.108083","DOIUrl":"10.1016/j.toxicon.2024.108083","url":null,"abstract":"<div><p>Food contamination with Aflatoxin B1 (AFB1) is a worldwide concern that adversely affects animal and human health. The study aimed to evaluate the protective effect of alpha lipoic acid (ALA) and/or co-enzyme Q10 (CQ10) against the harmful effects of AFB1 on the liver and kidneys. Fifty-six mature male Wistar Albino rats (180–200 g) were divided into seven groups, each with eight rats: (1) saline was given as a control, (2) ALA (100 mg/kg bw/day) was given by stomach gavage for fifteen days, and (3) CQ10 (10 mg/kg bw/day) was given by stomach gavage for fifteen days. Group (4) orally given AFB1 (2.5 mg/kg bw) on days 12th and 14th, (5) received AFB1 and ALA, (6) received AFB1 and CQ10, and (7) received AFB1, ALA, and CQ10, as previously described in the ALA, CQ10, and AFB1 groups. After the exposure to AFB1, a significant increase in liver markers (AST, ALT, ALP, and LDH) and renal function tests (BUN and creatinine) was observed compared with the control. ALA and/or CQ10 significantly reduced enzymes of liver and renal functions, as compared with AFB1. AFB1 exposure threw off the balance between oxidants and antioxidants. Still, ALA and/or CQ10 made oxidative stress (MDA, NO, and 8-OHdG) much lower and antioxidant activities (GSH, GSH-Px, SOD, and CAT) much higher. When we used the two together, the activities matched the control levels. Interestingly, this study shows that ALA and CQ10 significantly lowered IL-1β, IL-6, and TNF-α levels compared to the control values when used together after AFB1 exposure caused robust inflammation. Some CQ10 treatment parameters significantly outperformed those of ALA. ALA and CQ10 together worked better than either one alone to protect against AFB1-induced toxicity in the hepatic and renal parenchyma in terms of reducing inflammation, preventing DNA damage, and fighting free radicals.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"249 ","pages":"Article 108083"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120706","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}
引用次数: 0
V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins V-ToCs(毒液毒素聚类):蛇毒毒素序列和结构相似性研究工具。
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-31 DOI: 10.1016/j.toxicon.2024.108088
Konstantinos Kalogeropoulos , Vlad Rosca , Carol O'Brien , Charlotte Risager Christensen , Rahmat Grahadi , Christoffer Vinther Sørensen , Max D. Overath , Diego Ruiz Espi , David E. Jenkins , Ulrich auf dem Keller , Andreas H. Laustsen , Thomas J. Fryer , Timothy P. Jenkins
{"title":"V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins","authors":"Konstantinos Kalogeropoulos ,&nbsp;Vlad Rosca ,&nbsp;Carol O'Brien ,&nbsp;Charlotte Risager Christensen ,&nbsp;Rahmat Grahadi ,&nbsp;Christoffer Vinther Sørensen ,&nbsp;Max D. Overath ,&nbsp;Diego Ruiz Espi ,&nbsp;David E. Jenkins ,&nbsp;Ulrich auf dem Keller ,&nbsp;Andreas H. Laustsen ,&nbsp;Thomas J. Fryer ,&nbsp;Timothy P. Jenkins","doi":"10.1016/j.toxicon.2024.108088","DOIUrl":"10.1016/j.toxicon.2024.108088","url":null,"abstract":"<div><p>Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2000 known snake venom toxins. Indeed, by identifying similarities (i.e., conserved epitopes) across these different toxins, it is possible to design cross-reactive treatments, such as broadly-neutralising antibodies, that target these similarities. Therefore, in this project, we built an automated pipeline that generates sequence and structural distance matrices and homology trees across all available snake venom toxin sequences and structures. To facilitate analysis, we also developed a user-friendly and high-throughput visualisation tool, coined “Venom TOxin CluStering” (V-ToCs). This tool allows researchers to easily investigate sequence and structure patterns in snake venom toxins for a wide array of purposes, such as elucidating toxin evolution, and will also hopefully help guide the discovery and development of increasingly broadly-neutralising antivenoms in the near future.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108088"},"PeriodicalIF":2.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0041010124006603/pdfft?md5=1902cf2bd0beb8cef4da38c904242c76&pid=1-s2.0-S0041010124006603-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Snakebites by venomous snakes in Brazilian serpentaria and zoos over a 10-year period (2012–2021) 10 年间(2012-2021 年)巴西蛇园和动物园毒蛇咬伤情况
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-30 DOI: 10.1016/j.toxicon.2024.108082
Fábio Bucaretchi , Yasmin Trindade da Silva , Thalita Mendes Mitsunaga , Eduardo Mello De Capitani , Nelson Jorge da Silva Jr , Stephen Hyslop
{"title":"Snakebites by venomous snakes in Brazilian serpentaria and zoos over a 10-year period (2012–2021)","authors":"Fábio Bucaretchi ,&nbsp;Yasmin Trindade da Silva ,&nbsp;Thalita Mendes Mitsunaga ,&nbsp;Eduardo Mello De Capitani ,&nbsp;Nelson Jorge da Silva Jr ,&nbsp;Stephen Hyslop","doi":"10.1016/j.toxicon.2024.108082","DOIUrl":"10.1016/j.toxicon.2024.108082","url":null,"abstract":"<div><p>Despite the wide range of institutions that maintain venomous snakes in captivity in Brazil there are no comprehensive data on the occurrence of snakebites and envenomations in these places. We examined the range of native and exotic species of venomous snakes kept by Brazilian zoos and serpentaria (scientific and commercial) and assessed the frequency of snakebites in workers handling these snakes during a 10-year period (2012–2021). Twenty-two (73.3%) of 30 institutions returned a standard questionnaire, including 15 serpentaria and 7 zoos that together kept 10,607 venomous snakes in 2022/2023. Commercial and scientific serpentaria had many more snakes (n = 10,550, consisting of 10,499 native specimens and 51 exotic specimens) than zoos (n = 57 native specimens), with two genera accounting for the majority of native species (<em>Bothrops</em> spp. = 84.5% and <em>Crotalus durissus</em> ssp. = 13.5%). Thirty-seven snakebites were reported and involved primarily the hands (33), seven of which occurred during venom extraction and 30 in other circumstances, most of them while handling/manipulating the cages or snake boxes (10) and restraining (9) or feeding (5) the snake. In addition, there were two cases of venom accidently sprayed on the face, including the eyes. Most bites were caused by <em>Bothrops</em> spp. (31), followed by <em>C. durissus</em> ssp. (4), <em>Lachesis muta</em> (1) and <em>Micrurus corallinus</em> (1). Thirty-three bites (89.2%) were treated with antivenom, with four bites to the fingers by <em>Bothrops</em> spp. resulting in local functional sequelae. There were 366,918 venom extractions with a ratio of 1.9 bites/100,000 extractions; no bites were recorded in the six institutions that sedated the snakes prior to venom extraction, which accounted for 22.7% of all extractions. These findings show that although snakebites are rare in Brazilian zoos and serpentaria, severe envenomation may occur. The occurrence of snakebites could be reduced by measures such as sedation of the snakes before venom extraction.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"249 ","pages":"Article 108082"},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096518","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}
引用次数: 0
Aflatoxin removal and biotransformation aptitude of food grade bacteria from milk and milk products- at a glance 奶及奶制品中食品级细菌的黄曲霉毒素去除和生物转化能力--一览。
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-30 DOI: 10.1016/j.toxicon.2024.108084
Ami Patel
{"title":"Aflatoxin removal and biotransformation aptitude of food grade bacteria from milk and milk products- at a glance","authors":"Ami Patel","doi":"10.1016/j.toxicon.2024.108084","DOIUrl":"10.1016/j.toxicon.2024.108084","url":null,"abstract":"<div><p>Microorganisms are the only entities in the biosphere with an incomparable ability to employ diverse organic and inorganic compounds for growth and convert it to simple form that is no longer harmful to human health and environment. Food grade microorganisms such as lactic acid bacteria, bifidobacteria, propionibacteria as well as several yeast species are associated with food fermentation processes as well as have gained probiotic status owing to their noteworthy offerings in health stimulation as a natural gut microbiota in animals and humans. However, as biological agents little is known about their application for bioremediation and biotransformation aptitude. In context to this, aflatoxin M1 is a class of mycotoxins often associated with milk through consumption of fungus contaminated feed &amp; fodders by cattle and well documented for their adverse health effects. Therefore, current review summarizes significance of aflatoxins present in milk and dairy products in human life, their source, types &amp; health implications; food grade bacteria including probiotic strains and their mechanism of action involved in the removal of aflatoxin; and last section discusses the outcome of major studies showing aflatoxin reduction potential of food grade bacteria in milk and milk based products.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"249 ","pages":"Article 108084"},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112366","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}
引用次数: 0
Assessment of knowledge about first aid methods, diagnosis, and treatment of scorpion stings among health workers in Ouarzazate region, Morocco: A cross-sectional study 摩洛哥瓦尔扎扎特地区卫生工作者对蝎子蜇伤急救方法、诊断和治疗知识的评估:一项横断面研究。
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-30 DOI: 10.1016/j.toxicon.2024.108085
Hassan Alahyane , Bilal El-Mansoury , Adnane Hakem , Abdessamad Elmourid , Driss Ait Ali , Mohamed El Koutbi , Kamal Kaoutar , Brahim El Houate , Moulay Abdelmonaim El Hidan , Halima Gamrani , Abdelaati El Khiat
{"title":"Assessment of knowledge about first aid methods, diagnosis, and treatment of scorpion stings among health workers in Ouarzazate region, Morocco: A cross-sectional study","authors":"Hassan Alahyane ,&nbsp;Bilal El-Mansoury ,&nbsp;Adnane Hakem ,&nbsp;Abdessamad Elmourid ,&nbsp;Driss Ait Ali ,&nbsp;Mohamed El Koutbi ,&nbsp;Kamal Kaoutar ,&nbsp;Brahim El Houate ,&nbsp;Moulay Abdelmonaim El Hidan ,&nbsp;Halima Gamrani ,&nbsp;Abdelaati El Khiat","doi":"10.1016/j.toxicon.2024.108085","DOIUrl":"10.1016/j.toxicon.2024.108085","url":null,"abstract":"<div><p>Scorpion envenomation (SE) is a critical and immediate medical emergency. It represents a major public health concern with significant cause of illness and death, particularly in rural regions where scorpions are more prevalent. Of note, administering appropriate first aid to scorpion sting victims is one of the most effective ways to reduce mortality. Therefore, it is crucial to understand the level of knowledge of the healthcare workers in managing such cases. This work aims to assess the levels of knowledge on the diagnosis and management of scorpion stings, as well as the attitudes toward scorpion stings, among doctors and nurses in the Ouarzazate region of Morocco. Our results showed that the prevalent health care age group is 30–39 years, and in terms of experience, the majority had less than 5 years. Additionally, the majority of the participants had no knowledge regarding scorpions’ identification. Moreover, only half participants (healthcare workers) received basic training in the management of scorpion stings and almost all of them have not benefited from continuing training. Hence, the current study showed that the understanding of scorpion sting management among healthcare providers in Ouarzazate province is inadequate to ensure proper care for sting patients, and thus including scorpion sting management in the university programs of health care provides along with clinical practice are highly required.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108085"},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112367","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}
引用次数: 0
Effects of T-2 and deoxynivalenol mycotoxins on mouse spinal bone growth and integrity T-2和脱氧雪腐镰刀菌烯醇霉菌毒素对小鼠脊柱骨生长和完整性的影响
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-29 DOI: 10.1016/j.toxicon.2024.108079
Shuichu Hao , Cong Yao , Peilin Meng , Yumen Jia , li Liu , Chun Zhang
{"title":"Effects of T-2 and deoxynivalenol mycotoxins on mouse spinal bone growth and integrity","authors":"Shuichu Hao ,&nbsp;Cong Yao ,&nbsp;Peilin Meng ,&nbsp;Yumen Jia ,&nbsp;li Liu ,&nbsp;Chun Zhang","doi":"10.1016/j.toxicon.2024.108079","DOIUrl":"10.1016/j.toxicon.2024.108079","url":null,"abstract":"<div><p>Kashin-Beck Disease (KBD), an osteoarticular disorder, is influenced by various factors, including exposure to Deoxynivalenol (DON) and T-2 mycotoxins. This study systematically explored the impact of these mycotoxins on the development and structural resilience of spinal structures in mice, examining both isolated and combined effects. The experiment involved 72 male mice divided into nine groups, each subjected to varying concentrations of T-2, DON, or their combinations over four weeks. Rigorous monitoring included body weight, key indicators of bone metabolism, and cellular activities essential to bone health. Comprehensive evaluations using biomechanical analysis, x-ray, and micro-computed tomography (micro-CT) were conducted to assess alterations in spinal structure.</p><p>The findings revealed a pivotal aspect: mice exhibited a dose-dependent decline in body weight when exposed to individual mycotoxins, while simultaneous exposure produced an unanticipated antagonistic effect. Moreover, decreases were noted in levels of calcium, phosphorus, and vitamin D, coupled with changes in the activities of osteoblasts (increased) and osteoclasts (decreased), all intricately tied to the toxins' dosages and combinations. Notably, variations in the biomechanical properties corresponded with the mycotoxin dosage and blend, showing a decline in biomechanical strength. Micro-CT analyses further substantiated the profound toxic impact of the toxin dosage and mixtures on both the cortical and trabecular components of the spinal structures.</p><p>In summary, this investigation unequivocally illuminates the dose- and ratio-dependent deleterious impacts of DON and T-2 mycotoxins on the growth and structural soundness of spinal structures in mice. These findings highlight the urgent need for a comprehensive understanding of the potential hazards these toxins pose to bone health, providing invaluable guidance for future toxicological research and public health strategies.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108079"},"PeriodicalIF":2.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112377","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}
引用次数: 0
Enhancing snakebite management: The role of small molecule therapeutics in complementing antivenom strategies 加强蛇咬伤管理:小分子疗法在补充抗蛇毒血清策略中的作用。
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-27 DOI: 10.1016/j.toxicon.2024.108081
Glória Maria da Silva , Abhinandan Chowdhury
{"title":"Enhancing snakebite management: The role of small molecule therapeutics in complementing antivenom strategies","authors":"Glória Maria da Silva ,&nbsp;Abhinandan Chowdhury","doi":"10.1016/j.toxicon.2024.108081","DOIUrl":"10.1016/j.toxicon.2024.108081","url":null,"abstract":"<div><p>The variability in snake composition presents a significant challenge in accessing an effective broad-spectrum antivenom. These highly complex mixtures can result in numerous deleterious effects affecting thousands of individuals worldwide, particularly in Asia, sub-Saharan Africa, and Latin America. While the administration of antivenom remains a recommended treatment for snakebite envenomation and is the primary means to prevent systemic damage, there are limitations concerning specificity, reversal of local effects, and economic factors that hinder the availability of these antibodies. In this review, we have compiled information on the use of small molecule therapeutics in initial first-aid treatments before antivenom administration. These enzyme inhibitors have shown promise as viable candidates to broaden our treatment approaches, simplify procedures, reduce costs, and improve the clinical outcomes of affected patients.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"249 ","pages":"Article 108081"},"PeriodicalIF":2.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093911","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}
引用次数: 0
Evaluation of genotoxicity and teratogenicity of phillyrin 评估菲利林的遗传毒性和致畸性。
IF 2.6 4区 医学
Toxicon Pub Date : 2024-08-26 DOI: 10.1016/j.toxicon.2024.108080
Xuemin Li , Liru Wang , Shuqin Li , Junfeng Huo , Linxiu Bian , Ying Zhang , Xiaorui Wang , Jie Yao
{"title":"Evaluation of genotoxicity and teratogenicity of phillyrin","authors":"Xuemin Li ,&nbsp;Liru Wang ,&nbsp;Shuqin Li ,&nbsp;Junfeng Huo ,&nbsp;Linxiu Bian ,&nbsp;Ying Zhang ,&nbsp;Xiaorui Wang ,&nbsp;Jie Yao","doi":"10.1016/j.toxicon.2024.108080","DOIUrl":"10.1016/j.toxicon.2024.108080","url":null,"abstract":"<div><p>Phillyrin is extracted from <em>Forsythia suspensa</em> (Thunb.) Vahl, is significantly higher in (unripe Forsythiae Fructus) Qing qiao than in (ripe Forsythiae Fructus) Lao qiao fruits of the plant. However, the toxicity of phillyrin has not been adequately investigated. The study investigates the genetic and teratogenic effects of phillyrin to determine its safety profile. Assessing the genotoxicity and teratogenicity of phillyrin involved various tests, such as the bacterial reverse mutation assay, mammalian erythrocyte micronucleus assay, spermatocyte chromosome aberration assay, and teratogenicity assay. The results demonstrated that phillyrin exhibited no discernible impact on the following: number of colonies that spontaneously revert for <em>Salmonella typhimurium</em> TA 97, TA98, TA100, TA102, and TA1535, frequency of bone marrow polychromatic erythrocytes, and the rate of chromosomal aberrations. In the teratogenicity test, the pregnant rats exhibited no signs of toxicity or abnormal changes, and the growth, embryonic development, and visual anatomy of each pup were normal. In comparison with the negative control group, there were no significant differences in fetal body weight, mortality, deformity rate, malformed nest rate, gravid uterus weight, average number of fetuses per litter, fetal body length, or visceral and skeletal development in each dose group. In conclusion, these findings provide evidence that phillyrin does not exhibit genotoxic or teratogenic effects, supporting its potential safety for pharmacological applications.</p></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"249 ","pages":"Article 108080"},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093912","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}
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