Toxins最新文献 - Book学术

The Effect of Micro-Focused Ultrasound Treatment on Intradermal Botulinum Toxin Type A Injection.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-19 DOI: 10.3390/toxins17030147

Sarawin Harnchoowong, Natthachat Jurairattanaporn, Vasanop Vachiramon

{"title":"The Effect of Micro-Focused Ultrasound Treatment on Intradermal Botulinum Toxin Type A Injection.","authors":"Sarawin Harnchoowong, Natthachat Jurairattanaporn, Vasanop Vachiramon","doi":"10.3390/toxins17030147","DOIUrl":"10.3390/toxins17030147","url":null,"abstract":"Botulinum toxin type A (BoNT-A) injection and micro-focused ultrasound with visualization (MFU-V) are becoming increasingly popular for various esthetic conditions. However, performing MFU-V subsequently to BoNT-A injection may diminish the efficacy of BoNT-A. Previous reports have indicated the impact of various energy-based devices on BoNT-A. Nevertheless, the influence of MFU-V on BoNT-A has yet to be investigated. Thus, this study aims to evaluate the effect of MFU-V on BoNT-A injection and to determine the optimal interval between each treatment. A randomized controlled study was conducted on 15 subjects. Each participant was assigned to receive four sites of intradermal BoNT-A injection on their forehead. Following BoNT-A injection, these locations were randomized to receive either no MFU-V treatment or further treatment with MFU-V (superficial transducer, 10.0 MHz, 1.5 mm) on the same day, Day 7, or Day 14. On Day 28 following injection, the anhidrosis area was measured using the iodine starch test to objectively evaluate the result. In comparison to the control site (1.10 cm2), the anhidrotic area was significantly smaller in all MFU-V treated sites (0.74 cm2 in immediate MFU-V treatment, p < 0.001; 0.90 cm2 in MFU-V Day 7, p = 0.005; 0.93 cm2 in MFU-V Day 14, p = 0.021). There were no serious and esthetic complications reported in our study. In conclusion, MFU-V with a superficial depth transducer significantly reduced the efficacy of intradermal BoNT-A injection, especially within two weeks following BoNT-A injection. After BoNT-A injection, we recommend MFU-V treatment should be avoided for at least two weeks. Further study is required to evaluate the optimal interval between these two treatments.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Snake Venom Makeover: Age-Dependent Variations in Procoagulant Biochemistry of Egyptian Saw-Scaled Viper (Echis pyramidum pyramidum) Venom.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-19 DOI: 10.3390/toxins17030149

Alex Barker, Lee Jones, Lachlan A Bourke, Lorenzo Seneci, Abhinandan Chowdhury, Aude Violette, Rudy Fourmy, Raul Soria, Matt Aldridge, Bryan G Fry

{"title":"Snake Venom Makeover: Age-Dependent Variations in Procoagulant Biochemistry of Egyptian Saw-Scaled Viper (Echis pyramidum pyramidum) Venom.","authors":"Alex Barker, Lee Jones, Lachlan A Bourke, Lorenzo Seneci, Abhinandan Chowdhury, Aude Violette, Rudy Fourmy, Raul Soria, Matt Aldridge, Bryan G Fry","doi":"10.3390/toxins17030149","DOIUrl":"10.3390/toxins17030149","url":null,"abstract":"Echis species (saw-scaled vipers) are WHO Category 1 medically significant venomous snakes with potent procoagulant venoms, which cause lethal venom-induced consumptive coagulopathy in human victims. Despite clinical presentations of bites varying significantly between individuals within the same species, the contribution of age-related changes in the venom biochemistry has not been investigated. This study investigated the ontogenetic changes in Echis pyramidum pyramidum venom and its impact on therapeutic efficacy. The efficacy of various antivenoms (Echitab, Echitab+ ICP, Inosan MENA, Inosan Pan African, and SAVP-Echis) was tested against both venom phenotypes. While both neonate and adult venoms were procoagulant, there were differences in the underlying biochemistry. Neonate venom was found to potently pathophysiologically activate Factor VII and Factor X, and to a lesser degree Factor XII. In contrast, adult venom was a slower clotter, less potent in activating FVII, equipotent with neonate venom on FXII, and inactive on FX. This is the first documentation of FVII and FXII activation for any Echis venom. The significant ontogenetic toxicological variations in Echis species were shown to impact antivenom efficacy. Among the tested antivenoms, SAVP-Echis was the most effective against both venom phenotypes, with adult venom being better neutralized. These findings suggest the need for a reconsideration of venom mixture selection in antivenom production through the inclusion of neonate venom. Additionally, the results indicate differential ontogenetic predatory ecology, providing a foundation for future natural history investigations.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Effects of a Multicomponent Mycotoxin Detoxifying Agent on Health and Performance of Weaned Pigs Under Combined Dietary Exposure to Deoxynivalenol (DON) and Zearalenone (ZEN).

IF 3.9 3区医学

Toxins Pub Date : 2025-03-19 DOI: 10.3390/toxins17030146

Jog Raj, Panagiotis Tassis, Klaus Männer, Hunor Farkaš, Zdenka Jakovčević, Marko Vasiljević

{"title":"Effects of a Multicomponent Mycotoxin Detoxifying Agent on Health and Performance of Weaned Pigs Under Combined Dietary Exposure to Deoxynivalenol (DON) and Zearalenone (ZEN).","authors":"Jog Raj, Panagiotis Tassis, Klaus Männer, Hunor Farkaš, Zdenka Jakovčević, Marko Vasiljević","doi":"10.3390/toxins17030146","DOIUrl":"10.3390/toxins17030146","url":null,"abstract":"The aim of the present study was to evaluate the efficacy of a multicomponent mycotoxin detoxifying agent (MMDA, MYCORAID, Patent Co, Mišićevo, Serbia) in weaned pigs receiving contaminated feed with deoxynivalenol (DON) and zearalenone (ZEN). In total, 168 pigs were equally allocated in four experimental groups from day 25 to day 66 of age. The T1 group received feed without mycotoxins or MMDA. The pigs in group T2 received contaminated feed (CF) with 1.5 mg of DON/kg feed and 0.9 mg of ZEN/kg feed for the first two weeks and 1.2 mg of DON/kg feed and 0.9 mg of ZEN/kg feed for the rest of the trial period, without the addition of MMDA. Groups T3 and T4 received the CF with the addition of 1.5 g of MMDA/kg feed (T3), or 3 g of MMDA/kg feed (T4). Performance parameters, stress, and inflammatory biomarkers, as well as mycotoxin residues in liver, kidney, and muscle tissue were assessed. The results demonstrated improved average daily gain (ADG) and feed conversion ratio (FCR) along with reduced DON residues in kidney samples in groups T3 and T4 when compared with the T2 group. Although a typical dose-response relationship was not present in all parameter alterations, the results of the study proved the efficacy of the test product with improved growth performance and reduced mycotoxins absorption under the concurrent DON and ZEN exposure conditions and supported its use as a mitigating tool against mycotoxicosis under field conditions.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Incidence of Dysphagia and Comorbidities in Patients with Cervical Dystonia, Analyzed by Botulinum Neurotoxin Treatment Exposure.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-19 DOI: 10.3390/toxins17030148

Richard L Barbano, Bahman Jabbari, Marjan Sadeghi, Ahunna Ukah, Emma Yue, Kimberly Becker Ifantides, Nuo-Yu Huang, David Swope

{"title":"Incidence of Dysphagia and Comorbidities in Patients with Cervical Dystonia, Analyzed by Botulinum Neurotoxin Treatment Exposure.","authors":"Richard L Barbano, Bahman Jabbari, Marjan Sadeghi, Ahunna Ukah, Emma Yue, Kimberly Becker Ifantides, Nuo-Yu Huang, David Swope","doi":"10.3390/toxins17030148","DOIUrl":"10.3390/toxins17030148","url":null,"abstract":"Dysphagia is prevalent in patients with cervical dystonia (CD) and is a potential adverse event in patients treated with botulinum neurotoxin (BoNT) for CD. Real-world studies may provide a better understanding of the incidence and potential risk factors of dysphagia after BoNT administration. This retrospective cohort study used longitudinal patient-level data from Optum's de-identified Market Clarity Data to evaluate rates of dysphagia in patients with CD exposed and unexposed to BoNT. Patients ≥18 years of age with ≥2 CD diagnoses ≥30 days apart during the study period (1 January 2017-30 September 2021) who had ≥180 days of continuous health plan enrollment prior to the cohort entry date (first CD diagnosis) were included. Overall, the mean (SD) age of all CD patients (Cohort 1; N = 81,884) was 54.00 (16.21) years, and they were mostly female (67.9%) and white (76.96%). BoNT-Exposed patients (Cohort 2; N = 19,244) had a higher incidence of dysphagia (16.3%) and comorbid conditions when compared with BoNT-Unexposed patients (Cohort 3; N = 61,154 [12.1%]). Overall, patients with pre-existing dysphagia, other dystonias, and comorbid neurologic conditions at baseline also had higher proportions of dysphagia. This real-world analysis indicates that comorbid conditions predispose patients with CD to a greater dysphagia risk during treatment.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-18 DOI: 10.3390/toxins17030145

Pei Xie, Huijun Liu, Xingli Huo, Junlong Chen, Yu Li, Yu Huang, Zongning Yin

{"title":"Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury.","authors":"Pei Xie, Huijun Liu, Xingli Huo, Junlong Chen, Yu Li, Yu Huang, Zongning Yin","doi":"10.3390/toxins17030145","DOIUrl":"10.3390/toxins17030145","url":null,"abstract":"Acute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and its dysregulation leads to protein misfolding and amyloid aggregation. Glycosylation dynamics are implicated in several pathologies, including inflammation, cancer, and AKI, highlighting the therapeutic potential of regulating glycosylation and preventing aggregation in AKI treatment. This study investigates the effect of nafamostat mesylate (NM) on protein glycosylation and amyloid aggregation in vivo. Using optical spectroscopy and other analytical techniques, we demonstrate that NM restores glycosylation levels and inhibits protein aggregation in aristolochic-acid-induced acute kidney injury. The mechanism likely involves enzymatic modulation that corrects hypoglycosylation and prevents amyloid aggregation, promoting proper protein folding and enhancing its stability. These findings suggest that NM may provide a novel therapeutic strategy for AKI and other glycosylation-related diseases, underscoring the potential for early intervention and treatment of these conditions.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Ablation of Gut Microbiota Alleviates DON-Induced Neurobehavioral Abnormalities and Brain Damage in Mice.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-18 DOI: 10.3390/toxins17030144

Yujing Cui, Samuel Kumi Okyere, Haoyue Guan, Zixuan Hua, Youtian Deng, Huidan Deng, Junliang Deng

{"title":"Ablation of Gut Microbiota Alleviates DON-Induced Neurobehavioral Abnormalities and Brain Damage in Mice.","authors":"Yujing Cui, Samuel Kumi Okyere, Haoyue Guan, Zixuan Hua, Youtian Deng, Huidan Deng, Junliang Deng","doi":"10.3390/toxins17030144","DOIUrl":"10.3390/toxins17030144","url":null,"abstract":"Background: Deoxynivalenol (DON) poses a threat to animal and human health, particularly causing damage to the nervous system. Intestinal flora can regulate the nervous system through the gut-brain axis; however, there is currently a lack of evidence on the effect of changing the intestinal flora on the damage to the nervous system caused by DON. Therefore, this study aims to investigate the effect of gut microbiota ablation on neurotoxicity induced by exposure to deoxynivalenol.Methods: One hundred-twenty (120) specific pathogen-free (SPF) male C57BL/6j mice were randomly divided into four groups (control group, microbiota-uncleaned group + 5 mg/kg/BW DON, microbiota-cleared group, and microbiota-cleared group + 5 mg/kg/BW DON). The open field and Morris behavior tests were used to evaluate behavior changes after DON exposure. After 14 days of treatment, the mice were euthanized and brain tissues were collected for further analysis.Results: The tests showed that DON exposure led to anxiety and decreased learning ability in mice with no gut microbiota ablation. We also observed pathological changes including neuronal shrinkage, degeneration, and cortical edema in the mice with no microbiota ablation after DON exposure. In addition, the protein and mRNA levels of tight junction proteins and anti-inflammatory factors were decreased in the mice with no microbiota ablation after DON exposure compared with mice with ablated microbiota.Conclusions: We concluded that the presence of microbiota plays a key role in the neurotoxicity induced by DON; thus, ablation of the intestinal microbiota can effectively improve brain damage caused by DON.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cytotoxic Profiles of Beauvericin, Citrinin, Moniliformin, and Patulin and Their Binary Combinations: A Literature-Based Comparison and Experimental Validation in SH-SY5Y Cells.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-17 DOI: 10.3390/toxins17030143

Claudia Moyano-López, Luna Bridgeman, Cristina Juan, Ana Juan-García

{"title":"Cytotoxic Profiles of Beauvericin, Citrinin, Moniliformin, and Patulin and Their Binary Combinations: A Literature-Based Comparison and Experimental Validation in SH-SY5Y Cells.","authors":"Claudia Moyano-López, Luna Bridgeman, Cristina Juan, Ana Juan-García","doi":"10.3390/toxins17030143","DOIUrl":"10.3390/toxins17030143","url":null,"abstract":"Mycotoxins are toxic compounds found in food and feed that pose significant risks to human and animal health. This work reviews recent studies on the cytotoxic effects of four mycotoxins: beauvericin (BEA), citrinin (CTN), moniliformin (MON), and patulin (PAT) in various cell lines. Additionally, an experimental study evaluates the effects of these mycotoxins and their binary combinations on human neuroblastoma cells (SH-SY5Y) after 24 and 48 h of exposure using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. This analysis is driven by the additional risks posed by the frequent occurrence of these combinations in agricultural and food products, as well as the lack of studies addressing their effects, interactions, and regulatory frameworks. This research focuses on comparing the cytotoxicity data obtained in the SH-SY5Y cell line with previously reported findings in the literature for other cell lines exposed to BEA, CTN, MON, and PAT, individually and in binary combination. The literature highlights significant scientific interest in understanding the cytotoxic effects of these mycotoxins, with findings varying based on exposure time and concentration. Experimentally, PAT demonstrated the highest toxicity in SH-SY5Y cells, while MON was the least toxic. Among combinations, BEA + MON and CTN + PAT showed the greatest reduction in cell viability. However, medium inhibitory concentration (IC50) values were not reached for most combinations involving MON, reflecting its lower potency under the studied conditions. These findings underscore the importance of further investigation and enhanced regulations to address the health risks posed by mycotoxins, as their cytotoxic effects remain a pressing issue in food safety.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Long-Term Improvement of Gait Kinematics in Young Children with Cerebral Palsy Treated with Botulinum Toxin Injections and Integrated/Intensive Rehabilitation: A 5-Year Retrospective Observational Study.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-15 DOI: 10.3390/toxins17030142

Weronika Pyrzanowska, Magdalena Chrościńska-Krawczyk, Marcin Bonikowski

{"title":"Long-Term Improvement of Gait Kinematics in Young Children with Cerebral Palsy Treated with Botulinum Toxin Injections and Integrated/Intensive Rehabilitation: A 5-Year Retrospective Observational Study.","authors":"Weronika Pyrzanowska, Magdalena Chrościńska-Krawczyk, Marcin Bonikowski","doi":"10.3390/toxins17030142","DOIUrl":"10.3390/toxins17030142","url":null,"abstract":"Introduction: Patients with cerebral palsy (CP) present mobility limitations that alter their activity and participation in social life. This study aimed to assess changes in gait kinematic measurements using the Observational Gait Scale (OGS) and preselected parameters related to the foot, knee, and hip in children with CP who received repeated BoNT-A injections within a rehabilitation treatment over a five-year follow-up period.Material and methods: This single-center retrospective observational study included 200 consecutive children with bilateral CP (GMFCS I-IV). The five-year follow-up period was analyzed. Patients received between 5 and 10 BoNT-A treatments (mean 7.6 ± 2.3), with total doses per session varying from 20 units/kg to 30 units/kg for ABOBoNT-A and from 10 units/kg to 20 units/kg for OnaBoNT-A. In most cases, multilevel injections were performed, including in the hip flexors and adductors, knee flexors, and foot plantar flexors.Results: The mean age of the patients at the beginning was 32.23 months (±6.96). The OGS score improved in 74.5% and 76.5% of the patients, and deterioration occurred in 8.5% and 7% of patients for the right and left lower extremities, respectively. The changes in the OGS typically ranged from 1 to 4 points. Significant improvements in the knee position at midstance, initial foot contact, foot contact at midstance, timing of heel rise, and knee and hip positions at terminal stance were observed.Conclusions: The data from our retrospective observational study show a significant, long-term, positive effect of integrated treatment on gait kinematics in patients with CP in a homogenous group of young children with bilateral spastic cerebral palsy.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Selective Modulation of Osteoclast Function by Bothrops moojeni Venom and Its Fractions: Implications for Therapeutic Targeting in Bone Diseases.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-15 DOI: 10.3390/toxins17030141

Fernanda D'Amélio, Hugo Vigerelli, Isabel de Fátima Correia Batista, Rodrigo Pinheiro Araldi, Álvaro R B Prieto-da-Silva, Daniel Carvalho Pimenta, Irina Kerkis

{"title":"Selective Modulation of Osteoclast Function by Bothrops moojeni Venom and Its Fractions: Implications for Therapeutic Targeting in Bone Diseases.","authors":"Fernanda D'Amélio, Hugo Vigerelli, Isabel de Fátima Correia Batista, Rodrigo Pinheiro Araldi, Álvaro R B Prieto-da-Silva, Daniel Carvalho Pimenta, Irina Kerkis","doi":"10.3390/toxins17030141","DOIUrl":"10.3390/toxins17030141","url":null,"abstract":"Our study explores the differential effects of Bothrops moojeni venom and its fractions on osteoclast (OC) morphology, function, and osteoclastogenesis. The crude venom and its high-molecular-weight (HMW) fraction disrupt critical OC processes, including F-actin ring formation and mitochondrial distribution, thereby impairing bone resorption. These components primarily target cytoskeletal integrity and transcription regulation, with the OBSCN gene playing a direct role in OC function. In contrast, the low-molecular-weight (LMW) fraction selectively modulates OCs without significant cytoskeletal alterations. It influences vital cellular signaling pathways, notably through FNIP1 and FNIP2, essential for OC differentiation and function. This suggests a more targeted therapeutic approach with potentially fewer off-target effects. The venom also alters cytokine production, increasing IL-6 and IL-10 levels. Elevated IL-6 levels promote osteoclastogenesis and bone resorption, while IL-10 appears to counterbalance these effects through a regulatory feedback mechanism. Secretome analysis reveals that the crude venom and HMW fraction disrupt proteins involved in membrane trafficking and structural integrity. In contrast, the LMW fraction influences matrix remodeling, energy metabolism, and gene regulation. Gene interaction analysis LMW fraction post-treatment identifies FNIP1 and FNIP2 as critical targets involved in osteoclastogenesis. The observed changes in gene expression, including those related to immune response, energy metabolism, and chromatin remodeling, provide insights into the venom's impact on bone health. Overall, the LMW fraction shows promise for drug development due to its selective implications and potential for fewer side effects, offering a more precise approach to treating bone diseases.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications.

IF 3.9 3区医学

Toxins Pub Date : 2025-03-14 DOI: 10.3390/toxins17030136

Diana Carolina Zona Rubio, Diana Marcela Aragón, Izabel Almeida Alves

{"title":"Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications.","authors":"Diana Carolina Zona Rubio, Diana Marcela Aragón, Izabel Almeida Alves","doi":"10.3390/toxins17030136","DOIUrl":"10.3390/toxins17030136","url":null,"abstract":"Active compounds from natural sources, particularly snake venoms, are crucial for pharmaceutical development despite challenges in drug discovery. Snake venoms, historically used for medicinal purposes, contain bioactive peptides and enzymes that show therapeutic potential for conditions such as arthritis, asthma, cancer, chronic pain, infections and cardiovascular diseases. The objective of this study was to examine pharmacological and biomedical innovations by identifying the key research trends, the most studied snake species, and their therapeutic applications. A systematic review of patents related to snake venoms was conducted using the European Patent Office database, Espacenet, covering 2014 to mid-2024. The search employed the keyword \"venom,\" applying IPC classification A61K38/00, resulting in 31 patents after screening. A PubMed survey on \"snake venom derivatives innovations\" was conducted to compare the scientific literature volume with the identified patents. This review highlights the therapeutic potential of snake venom-derived products for coagulation disorders, cancer, inflammation, and pain management. Despite challenges in pharmacokinetics and venom variability, advancements in biotechnology offer promise for personalized therapies. The future of snake venom-based treatments appears promising for addressing complex medical conditions.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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