PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, q=subject:"Toxicology"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&sort=Date,+newest+first&unformattedQuery=subject:%22Toxicology%22All PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-28T21:43:47ZReflected generalized concentration addition and Bayesian hierarchical models to improve chemical mixture predictionDaniel ZilberKyle Messier10.1371/journal.pone.02986872024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Daniel Zilber, Kyle Messier</p>
Environmental toxicants overwhelmingly occur together as mixtures. The variety of possible chemical interactions makes it difficult to predict the danger of the mixture. In this work, we propose the novel Reflected Generalized Concentration Addition (RGCA), a piece-wise, geometric technique for sigmoidal dose-responsed inverse functions that extends the use of generalized concentration addition (GCA) for 3+ parameter models. Since experimental tests of all relevant mixtures is costly and intractable, we rely only on the individual chemical dose responses. Additionally, RGCA enhances the classical two-step model for the cumulative effects of mixtures, which assumes a combination of GCA and independent action (IA). We explore how various clustering methods can dramatically improve predictions. We compare our technique to the IA, CA, and GCA models and show in a simulation study that the two-step approach performs well under a variety of true models. We then apply our method to a challenging data set of individual chemical and mixture responses where the target is an androgen receptor (Tox21 AR-luc). Our results show significantly improved predictions for larger mixtures. Our work complements ongoing efforts to predict environmental exposure to various chemicals and offers a starting point for combining different exposure predictions to quantify a total risk to health.Urinary proteomics reveals biological processes related to acute kidney injury in <i>Bothrops atrox</i> envenomingsLisele Maria Brasileiro-MartinsSofia Angiole CavalcanteThaís Pinto NascimentoAlexandre Vilhena Silva-NetoMarlon Dias Mariano SantosAmanda C. Camillo-AndradeJuliana de Saldanha da Gama FischerCaroline Coelho FerreiraLucas Barbosa OliveiraMarco Aurelio SartimAllyson Guimarães CostaManuela B. PuccaFan Hui WenAna Maria Moura-da-SilvaJacqueline SachettPaulo Costa CarvalhoPriscila Ferreira de AquinoWuelton M. Monteiro10.1371/journal.pntd.00120722024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Lisele Maria Brasileiro-Martins, Sofia Angiole Cavalcante, Thaís Pinto Nascimento, Alexandre Vilhena Silva-Neto, Marlon Dias Mariano Santos, Amanda C. Camillo-Andrade, Juliana de Saldanha da Gama Fischer, Caroline Coelho Ferreira, Lucas Barbosa Oliveira, Marco Aurelio Sartim, Allyson Guimarães Costa, Manuela B. Pucca, Fan Hui Wen, Ana Maria Moura-da-Silva, Jacqueline Sachett, Paulo Costa Carvalho, Priscila Ferreira de Aquino, Wuelton M. Monteiro</p>
Acute kidney injury (AKI) is a critical systemic complication caused by <i>Bothrops</i> envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of <i>Bothrops atrox</i> snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI’s urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by <i>Bothrops</i> envenoming. This work sheds light on physiological disturbances caused by <i>Bothrops</i> envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.Landscape of toxin-neutralizing therapeutics for snakebite envenoming (2015–2022): Setting the stage for an R&D agendaJuliette BorriJosé María GutiérrezCecilie KnudsenAbdulrazaq G. HabibMaya GoldsteinAndrew Tuttle10.1371/journal.pntd.00120522024-03-26T14:00:00Z2024-03-26T14:00:00Z<p>by Juliette Borri, José María Gutiérrez, Cecilie Knudsen, Abdulrazaq G. Habib, Maya Goldstein, Andrew Tuttle</p>
Background <p>Progress in snakebite envenoming (SBE) therapeutics has suffered from a critical lack of data on the research and development (R&D) landscape. A database characterising this information would be a powerful tool for coordinating and accelerating SBE R&D. To address this need, we aimed to identify and categorise all active investigational candidates in development for SBE and all available or marketed products.</p> Methodology/Principal findings <p>In this landscape study, publicly available data and literature were reviewed to canvas the state of the SBE therapeutics market and research pipeline by identifying, characterising, and validating all investigational drug and biologic candidates with direct action on snake venom toxins, and all products available or marketed from 2015 to 2022. We identified 127 marketed products and 196 candidates in the pipeline, describing a very homogenous market of similar but geographically bespoke products and a diverse but immature pipeline, as most investigational candidates are at an early stage of development, with only eight candidates in clinical development.</p> Conclusions/Significance <p>Further investment and research is needed to address the shortfalls in products already on the market and to accelerate R&D for new therapeutics. This should be accompanied by efforts to converge on shared priorities and reshape the current SBE R&D ecosystem to ensure translation of innovation and access.</p>Structural and functional characterization of sulfurtransferase from <i>Frondihabitans</i> sp. PAMC28461Hackwon DoDieu Linh NguyenYong-Yoon AhnYewon NamYoonJi KangHoeJung OhJisub HwangSe Jong HanKitae KimJun Hyuck Lee10.1371/journal.pone.02989992024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Hackwon Do, Dieu Linh Nguyen, Yong-Yoon Ahn, Yewon Nam, YoonJi Kang, HoeJung Oh, Jisub Hwang, Se Jong Han, Kitae Kim, Jun Hyuck Lee</p>
Sulfurtransferases transfer of sulfur atoms from thiols to acceptors like cyanide. They are categorized as thiosulfate sulfurtransferases (TSTs) and 3-mercaptopyruvate sulfurtransferases (MSTs). TSTs transfer sulfur from thiosulfate to cyanide, producing thiocyanate. MSTs transfer sulfur from 3-mercaptopyruvate to cyanide, yielding pyruvate and thiocyanate. The present study aimed to isolate and characterize the sulfurtransferase <i>Fr</i>ST from <i>Frondihabitans</i> sp. PAMC28461 using biochemical and structural analyses. <i>Fr</i>ST exists as a dimer and can be classified as a TST rather than an MST according to sequence-based clustering and enzyme activity. Furthermore, the discovery of activity over a wide temperature range and the broad substrate specificity exhibited by <i>Fr</i>ST suggest promising prospects for its utilization in industrial applications, such as the detoxification of cyanide.<i>In vitro</i> immunoreactivity and <i>in vivo</i> neutralization of <i>Trimeresurus gracilis</i> venom with antivenoms targeting four pit viper speciesPo-Chun ChuangJia-Wei ChenYuen-Ying ChanTsz-Chun TseYu-Wei ChiangTein-Shun Tsai10.1371/journal.pntd.00120702024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Po-Chun Chuang, Jia-Wei Chen, Yuen-Ying Chan, Tsz-Chun Tse, Yu-Wei Chiang, Tein-Shun Tsai</p>
Snakebite envenomation is a significant global health issue that requires specific antivenom treatments. In Taiwan, available antivenoms target a variety of snakes, but none specifically target <i>Trimeresurus gracilis</i>, an endemic and protected species found in the high mountain areas of Taiwan. This study evaluated the effectiveness of existing antivenoms against <i>T</i>. <i>gracilis</i> venom, focusing on a bivalent antivenom developed for <i>Trimeresurus stejnegeri</i> and <i>Protobothrops mucrosquamatu</i>s (TsPmAV), as well as monovalent antivenoms for <i>Deinagkistrodon acutus</i> (DaAV) and <i>Gloydius brevicaudus</i> (GbAV). Our research involved <i>in vivo</i> toxicity testing in mice and <i>in vitro</i> immunobinding experiments using (chaotropic) enzyme-linked immunosorbent assays, comparing venoms from four pit viper species (<i>T</i>. <i>gracilis</i>, <i>T</i>. <i>stejnegeri</i>, <i>P</i>. <i>mucrosquamatus</i>, and <i>D</i>. <i>acutus</i>) with three types of antivenoms. These findings indicate that TsPmAV partially neutralized <i>T</i>. <i>gracilis</i> venom, marginally surpassing the efficacy of DaAV. <i>In vitro</i> tests revealed that GbAV displayed higher binding capacities toward <i>T</i>. <i>gracilis</i> venom than TsPmAV or DaAV. Comparisons of electrophoretic profiles also reveal that <i>T</i>. <i>gracilis</i> venom has fewer snake venom C-type lectin like proteins than <i>D</i>. <i>acutus</i>, and has more P-I snake venom metalloproteases or fewer phospholipase A<sub>2</sub> than <i>G</i>. <i>brevicaudus</i>, <i>T</i>. <i>stejnegeri</i>, or <i>P</i>. <i>mucrosquamatus</i>. This study highlights the need for antivenoms that specifically target <i>T</i>. <i>gracilis</i>, as current treatments using TsPmAV show limited effectiveness in neutralizing local effects in patients. These findings provide crucial insights into clinical treatment protocols and contribute to the understanding of the evolutionary adaptation of snake venom, aiding in the development of more effective antivenoms for human health.Chitosan nanoparticles improve the effectivity of miltefosine against <i>Acanthamoeba</i>Alireza LatifiFariba EsmaeiliMehdi MohebaliSetayesh Yasami-KhiabaniMostafa RezaeianMohammad SoleimaniElham KazemiradAmir Amani10.1371/journal.pntd.00119762024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Alireza Latifi, Fariba Esmaeili, Mehdi Mohebali, Setayesh Yasami-Khiabani, Mostafa Rezaeian, Mohammad Soleimani, Elham Kazemirad, Amir Amani</p>
Background <p><i>Acanthamoeba</i> keratitis (AK) is a corneal sight-threatening infection caused by the free-living amoebae of the genus <i>Acanthamoeba</i>. Early and appropriate treatment significantly impacts visual outcomes. Mucoadhesive polymers such as chitosan are a potential strategy to prolong the residence time and bioavailability of the encapsulated drugs in the cornea. Regarding the recent administration of miltefosine (MF) for treating resistant AK, in the present study, we synthesized miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) and evaluated them against <i>Acanthamoeba</i>.</p> Methodology/Principal findings <p>Chitosan nanoparticles (CNPs) were prepared using the ionic gelation method with negatively charged tripolyphosphate (TPP). The zeta-potential (ZP) and the particle size of MF-CS-NPs were 21.8±3.2 mV and 46.61±18.16 nm, respectively. The release profile of MF-CS-NPs indicated linearity with sustained drug release. The cytotoxicity of MF-CS-NPs on the <i>Vero</i> cell line was 2.67 and 1.64 times lower than free MF at 24 and 48 hours. This formulation exhibited no hemolytic activity <i>in vitro</i> and ocular irritation in rabbit eyes. The IC<sub>50</sub> of MF-CS-NPs showed a significant reduction by 2.06 and 1.69-fold in trophozoites at 24 and 48 hours compared to free MF. Also, the MF-CS-NPs IC<sub>50</sub> in the cysts form was slightly decreased by 1.26 and 1.21-fold at 24 and 48 hours compared to free MF.</p> Conclusions <p>The MF-CS-NPs were more effective against the trophozoites and cysts than free MF. The nano-chitosan formulation was more effective on trophozoites than the cysts form. MF-CS-NPs reduced toxicity and improved the amoebicidal effect of MF. Nano-chitosan could be an ideal carrier that decreases the cytotoxicity of miltefosine. Further analysis in animal settings is needed to evaluate this nano-formulation for clinical ocular drug delivery.</p>“And this is the life jacket, the lifeline they’ve been wanting”: Participant perspectives on navigating challenges and successes of prescribed safer supplyNancy HendersonJohn MarrisKirsten Woodend10.1371/journal.pone.02998012024-03-22T14:00:00Z2024-03-22T14:00:00Z<p>by Nancy Henderson, John Marris, Kirsten Woodend</p>
Background <p>In 2021, 43% of drug toxicity deaths in Ontario were reported by public health units serving medium-sized urban and rural communities. Safer supply programs (SSPs) have been primarily established in large urban centres. Given this, the current study is based on an evaluation of a SSP based in a medium-sized urban centre with a large catchment area that includes rural and Indigenous communities. The aim of this research paper is to understand the challenges and successes of the nurse practitioner-led SSP from the perspective of program participants.</p> Methods <p>Interpretive description was used to understand the experiences of 14 participants accessing a SSP. Each participant was interviewed using a semi-structured approach, and 13 of the interviewees also completed surveys accessed through Qualtrics. An iterative process using NVivo software was used to code interviews, and a constant comparative data analysis approach was used to refine and categorize codes to themes.</p> Findings <p>Three overarching themes were the result of this analysis: feeling better, renewed hope, and safety. These three themes capture the experiences of participants in the SSP, including both the challenges and successes they faced.</p> Conclusion <p>The findings and subsequent discussion focus on both the key best practices of the program, and areas for future development and improvement. Despite barriers to services, prescribed SSPs are improving the lives of people who use drugs, and the current outcomes align with reports and evaluations from other SSPs across Canada.</p>Synthesis, molecular docking analysis, molecular dynamic simulation, ADMET, DFT, and drug likeness studies: Novel Indeno[1,2-<i>b</i>]pyrrol-4(1<i>H</i>)-one as SARS-CoV-2 main protease inhibitorsDavood GheidariMorteza MehrdadMohammad Bayat10.1371/journal.pone.02993012024-03-22T14:00:00Z2024-03-22T14:00:00Z<p>by Davood Gheidari, Morteza Mehrdad, Mohammad Bayat</p>
Background <p>The COVID-19 pandemic began in 2019 as a result of the advent of a novel coronavirus, SARS-CoV-2. At present, there are a limited number of approved antiviral agents for the treatment of COVID-19. Remdesivir, Molnupiravir, and Paxlovid have been approved by the FDA to treat COVID-19 infections. Research has shown that the main protease enzyme (M<sup>pro</sup>) of SARS-CoV-2 plays a crucial role in the enzymatic processing of viral polyproteins. This makes M<sup>pro</sup> an interesting therapeutic target for combating infections caused by emerging coronaviruses.</p> Methods <p>The pharmacological effects of pyrroles and their derivatives have a wide range of applications. In our study, we focused on synthesizing nine novel derivatives of 2-arylamino-dihydro-indeno[1,2-<i>b</i>] pyrrol-4(1<i>H</i>)-one, with a particular emphasis on their antiviral properties. Using in <i>silico</i> studies involving molecular docking and DFT analyses in the gas phase using the B3LYP/6-31++G(d,p) basis set, we studied these compounds with respect to their interactions with the M<sup>pro</sup> of SARS-CoV-2. The results of the docking analysis revealed that the synthesized compounds exhibited favorable inhibitory effects. Notably, compound 5f demonstrated the highest effectiveness against the target protein. Furthermore, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-<i>b</i>] pyrrol-4(1<i>H</i>)-one indicated their potential as promising candidates for further development as inhibitors targeting SARS-CoV-2. However, it is imperative to determine the in <i>vitro</i> efficacy of these compounds through comprehensive biochemical and structural analyses.</p>Identification of the single and combined acute toxicity of Cr and Ni with <i>Heterocypris</i> sp. and the quantitative structure-activity relationship (QSAR) modelChi SuYilong HuaYi LiuShu TaoFei JiaWenhui ZhaoWangyang Lin10.1371/journal.pone.03008002024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Chi Su, Yilong Hua, Yi Liu, Shu Tao, Fei Jia, Wenhui Zhao, Wangyang Lin</p>
Mining wastewater with heavy metals poses a serious threat to the ecological environment. However, the acute single and combined ecological effects of heavy metals, such as chromium (Cr) and nickel (Ni), on freshwater ostracods, and the development of relevant prediction models, remain poorly understood. In this study, <i>Heterocypris</i> sp. was chosen to investigate the single and combined acute toxicity of Cr and Ni. Then, the quantitative structure-activity relationship (QSAR) model was used to predict the combined toxicity of Cr and Ni. The single acute toxicity experiments revealed high toxicity for both Cr and Ni. In addition, Cr exhibited greater toxicity compared to Ni, as evidenced by its lower 96-hour half-lethal concentration (LC<sub>50</sub>) of 1.07 mg/L compared to 4.7 mg/L for Ni. Furthermore, the combined acute toxicity experiments showed that the toxicity of Cr-Ni was higher than Ni but lower than Cr. Compared with the concentration addition (CA) and independent action (IA) models, the predicted results of the QSAR model were more consistent with the experimental results for the Cr-Ni combined acute toxicity. So, the high accuracy of QSAR model identified its feasibility to predict the toxicity of heavy metal pollutants in mining wastewater.The effectiveness of botulinum toxin for temporomandibular disorders: A systematic review and meta-analysisRavinder S. SainiMuhammad Ali Abdullah AlmoyadRayan Ibrahim H. BinduhayyimSyed Altafuddin QuadriVishwanath GurumurthyShashit Shetty BavabeeduMohammed Saheer KuruniyanPunnoth Poonkuzhi NaseefSeyed Ali MosaddadArtak Heboyan10.1371/journal.pone.03001572024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Ravinder S. Saini, Muhammad Ali Abdullah Almoyad, Rayan Ibrahim H. Binduhayyim, Syed Altafuddin Quadri, Vishwanath Gurumurthy, Shashit Shetty Bavabeedu, Mohammed Saheer Kuruniyan, Punnoth Poonkuzhi Naseef, Seyed Ali Mosaddad, Artak Heboyan</p>
Objective <p>The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary objective of this study was to determine the effectiveness of BTX in pain reduction for TMDs compared to placebo and other treatments. The secondary outcomes evaluated were adverse events, maximum mouth opening, bruxism events, and maximum occlusal force.</p> Materials and methods <p>A literature search was performed on PubMed, Dimension Publication, Scopus, and Google Scholar. The RoB 2 tool was used for quality assessment. The mean differences in pain scores were estimated to measure the effect of BTX on pain reduction. For adverse events, the risk ratio for the incidence of side effects was calculated.</p> Results <p>Two hundred and sixty non-duplicate articles were identified; however, only 14 RCTS were included in this review. The total study population included 395 patients. The overall risk of bias showed a low to moderate quality of evidence. Results from 6 studies were reported only narratively; four studies were used for meta-analysis on pain reduction, and five were used for meta-analysis on adverse events. The control used in the meta-analysis was placebo injections. Results of the meta-analysis for pain reduction were statistically insignificant for the BTX group with mean differences at MD = −1.71 (95% CI, −2.87 to −0.5) at one month, -1.53 (95% CI, −2.80 to −0.27) at three months, and -1.33 (95% CI, −2.74 to 0.77) at six months. This showed that BTX treatment was not significantly better than placebo for a reduction in pain scores at 1, 3, and 6 months. Regarding safety, the placebo group showed a relative risk of 1.34 (95%CI, 0.48–6.78) and 1.17 (95%CI, 0.54–3.88) at 1 and 3 months respectively. However, the risks were not statistically significant. There was also no difference in the effectiveness of BTX compared to placebo and other treatments for maximum mouth opening, bruxism events, and maximum occlusal force.</p> Conclusion <p>BTX was not associated with better outcomes in terms of pain reduction, adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. More high-quality RCTs are needed to better understand this topic.</p>The polyglutamine domain is the primary driver of seeding in huntingtin aggregationAdam SkeensChathuranga SiriwardhanaSophia E. MassinopleMichelle M. WunderZachary L. EllisKaitlyn M. KeithTyler GirmanShelli L. FreyJustin Legleiter10.1371/journal.pone.02983232024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Adam Skeens, Chathuranga Siriwardhana, Sophia E. Massinople, Michelle M. Wunder, Zachary L. Ellis, Kaitlyn M. Keith, Tyler Girman, Shelli L. Frey, Justin Legleiter</p>
Huntington’s Disease (HD) is a fatal, neurodegenerative disease caused by aggregation of the huntingtin protein (htt) with an expanded polyglutamine (polyQ) domain into amyloid fibrils. Htt aggregation is modified by flanking sequences surrounding the polyQ domain as well as the binding of htt to lipid membranes. Upon fibrillization, htt fibrils are able to template the aggregation of monomers into fibrils in a phenomenon known as seeding, and this process appears to play a critical role in cell-to-cell spread of HD. Here, exposure of <i>C</i>. <i>elegans</i> expressing a nonpathogenic N-terminal htt fragment (15-repeat glutamine residues) to preformed htt-exon1 fibrils induced inclusion formation and resulted in decreased viability in a dose dependent manner, demonstrating that seeding can induce toxic aggregation of nonpathogenic forms of htt. To better understand this seeding process, the impact of flanking sequences adjacent to the polyQ stretch, polyQ length, and the presence of model lipid membranes on htt seeding was investigated. Htt seeding readily occurred across polyQ lengths and was independent of flanking sequence, suggesting that the structured polyQ domain within fibrils is the key contributor to the seeding phenomenon. However, the addition of lipid vesicles modified seeding efficiency in a manner suggesting that seeding primarily occurs in bulk solution and not at the membrane interface. In addition, fibrils formed in the presence of lipid membranes displayed similar seeding efficiencies. Collectively, this suggests that the polyQ domain that forms the amyloid fibril core is the main driver of seeding in htt aggregation.The beneficial effect of <i>Allium Cepa</i> bulb extract on reproduction of rats; A two-generation study on fecundity and sex hormonesSadia SuriSaira Saeed KhanSadaf NaeemZeb Un NisaNausheen AlamSaba MajeedSuresh KumarRafeeq Alam Khan10.1371/journal.pone.02949992024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Sadia Suri, Saira Saeed Khan, Sadaf Naeem, Zeb Un Nisa, Nausheen Alam, Saba Majeed, Suresh Kumar, Rafeeq Alam Khan</p>
<i>Allium Cepa Linn</i>. (Onions) has extensively been used in traditional medicine, is one of the important Allium species regularly used in our daily diet, and has been the source of robust phenolic compounds. The current study is intended to evaluate the fecundity-enhancing effect of <i>A</i>. <i>Cepa</i> on the reproductive performance of two successive generations of rats; F<sub>0</sub> and F<sub>1</sub>. <i>A</i>. <i>Cepa</i> extract was initially tested for in vitro antioxidant assay via DPPH and ROS, followed by in vivo toxicity testing. In the fecundity assessment, eighteen pairs of male and female rats (n = 36, 1:1, F<sub>0</sub> generation) were divided into three groups and dosed with 75mg/kg and 150 mg/kg daily of <i>A</i>. <i>Cepa</i> extract and saline respectively, up to pre-cohabitation, cohabitation, gestation and lactation period. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Various parameters like Hematological, Hormonal (FSH, LH, Testosterone, estradiol), antioxidant markers (SOD, Glutathione peroxidase) and lipid profile of F<sub>0</sub> and F<sub>1</sub> generations were assessed with evaluation of histopathology of male and female organs. Ethanolic extract of <i>A</i>. <i>Cepa</i> showed the greatest antioxidant potential in DPPH and ROS methods. The continued exposure of the F<sub>0</sub> and F<sub>1</sub> generations to <i>A</i>. <i>Cepa</i> extract did not affect body weight, fertility index, litter size, and survival index. However, semen pH, sperm motility, sperm count, sperm viability, and semen volume were significantly improved in both generations. We have found pronounced fecundity outcomes in both genders of F<sub>0</sub> and F<sub>1</sub> generations with <i>A</i>. <i>Cepa</i> 150mg/kg/day extract as compared to control. Results showed that <i>A</i>. <i>Cepa</i> significantly increased (P < 0.05) hemoglobin, follicular stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone and glutathione peroxidase activities, while total lipid, LDL, and cholesterol were significantly decreased (P < 0.05) in both generations. Histology of both generations of animals reveals enhanced spermatogenesis and enhanced folliculogenesis with improved architecture. Altogether, the present results suggest that <i>A</i>. <i>Cepa</i> extract improved fecundity in both male and female rats by improving hormonal activities and oxidative stress.Does the Wim Hof Method have a beneficial impact on physiological and psychological outcomes in healthy and non-healthy participants? A systematic reviewOmar AlmahayniLucy Hammond10.1371/journal.pone.02869332024-03-13T14:00:00Z2024-03-13T14:00:00Z<p>by Omar Almahayni, Lucy Hammond</p>
Introduction <p>Wim Hof, also known as the iceman, developed a method called Wim Hof Method (WHM) which he claims to have several benefits on physical and mental health. The aim of this systematic review is to identify and synthesise the results of the studies conducted on WHM on physiological and psychological health-related outcomes.</p> Materials and methods <p>This systematic review followed the PRISMA guidelines for systematic reviews. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022333209. Medline and Web of Science were searched and included studies from January 1, 2014, to July 4, 2022. Studies were included if they met the predetermined inclusion/exclusion criteria. Inclusion criteria included RCTs and cohort studies published in peer-reviewed journals, studies conducted on healthy individuals and people with pre-existing medical conditions (adolescents and adults over the age of 14), studies that included all three pillars (breathing, cold exposure, and commitment) of the WHM, and studies that only focused on Wim Hof breathing method (WHBM). Exclusion criteria included studies that discussed WHM but are not original experimental research or are not peer-reviewed, studies that included children under the age of 14, and studies that used methods similar to WHM, but not actually WHM, such as tummo meditation. The articles were assessed for risk of bias using RoB 2.0 and Scottish Intercollegiate Guidelines Network (SIGN) tools. The effects of WHM were categorised into physiological or psychological related outcomes and narrative synthesis was conducted.</p> Results <p>Nine papers were included in this review which consisted of eight individual trials. The findings suggest that the WHM may reduce inflammation in healthy and non-healthy participants as it increases epinephrine levels, causing an increase in interleukin-10 and a decrease in pro-inflammatory cytokines. Additionally, effect of WHBM on exercise performance showed mixed findings. Effects on respiratory parameters of minute ventilation, tidal volume, and breathing frequency were mixed following bouts of exercise.</p> Conclusion <p>Taken together, the findings of this review show promising use of WHM in the inflammatory response category. The focus of future studies should further investigate the benefits of WHM in non-healthy participants with inflammatory disorders and explore the use of Wim Hof breathing method to enhance exercise performance.</p>Constructed wetland as a green remediation technology for the treatment of wastewater from underground coal gasification processŁukasz JałowieckiAleksandra Strugała-WilczekKatarzyna PonikiewskaJacek BorgulatGrażyna PłazaKrzysztof Stańczyk10.1371/journal.pone.03004852024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Łukasz Jałowiecki, Aleksandra Strugała-Wilczek, Katarzyna Ponikiewska, Jacek Borgulat, Grażyna Płaza, Krzysztof Stańczyk</p>
The wastewater from underground coal gasification (UCG) process has extremely complex composition and high concentrations of toxic and refractory compounds including phenolics, aliphatic and aromatic hydrocarbons, ammonia, cyanides, hazardous metals and metalloids. So, the development of biological processes for treating UCG wastewater poses a serious challenge in the sustainable coal industry. The aim of the study was to develop an innovative and efficient wetland construction technology suitable for a treatment of UCG wastewater using available and low-cost media. During the bioremediation process the toxicity of the raw wastewater decreased significantly between 74%—99%. The toxicity units (TU) ranged from values corresponding to very high acute toxic for raw wastewater to non-toxic for effluents from wetland columns after 60 days of the experiment. The toxicity results correlated with the decrease of some organic and inorganic compounds such as phenols, aromatic hydrocarbons, cyanides, metals and ammonia observed during the bioremediation process. The removal percentage of organic compounds like BTEX, PAHs and phenol was around 99% just after 14 days of treatment. A similar removal rate was indicated for cyanide and metals (Zn, Cr, Cd and Pb). Concluded, in order to effectively assess remediation technologies, it is desirable to consider combination of physicochemical parameters with ecotoxicity measurements. The present findings show that wetland remediation technology can be used to clean-up the heavily contaminated waters from the UCG process. Wetland technology as a nature-based solution has the potential to turn coal gasification wastewater into usable recycled water. It is economically and environmentally alternative treatment method.Virulence genes, antimicrobial resistance profile, phylotyping and pathotyping of diarrheagenic <i>Escherichia coli</i> isolated from children in Southwest MexicoGabriela Tapia-PastranaMetztli Rojas-BautistaPilar Hernández-PérezOlegario Santiago-MartínezLucía C. Gómez-RodríguezVíctor M. Terrazas-LunaJacobo Montes-YedraAlfonso A. Bautista-AvendañoEduardo S. García-LópezNidia Leon-SicairosUriel A. Angulo-ZamudioAdrian Canizalez-Roman10.1371/journal.pone.03003042024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Gabriela Tapia-Pastrana, Metztli Rojas-Bautista, Pilar Hernández-Pérez, Olegario Santiago-Martínez, Lucía C. Gómez-Rodríguez, Víctor M. Terrazas-Luna, Jacobo Montes-Yedra, Alfonso A. Bautista-Avendaño, Eduardo S. García-López, Nidia Leon-Sicairos, Uriel A. Angulo-Zamudio, Adrian Canizalez-Roman</p>
Diarrheagenic <i>E</i>. <i>coli</i> (DEC) strains are one of the most important etiology factors causing diarrhea in children worldwide, especially in developing countries. DEC strains have characteristic virulence factors; however, other supplemental virulence genes (SVG) may contribute to the development of diarrhea in children. Therefore, this study aimed to determine the prevalence of DEC in children with diarrhea in southwestern Mexico and to associate childhood symptoms, SVG, and pathotypes with diarrhea-causing DEC strains. DEC strains were isolated from 230 children with diarrhea aged 0–60 months from the state of Oaxaca, southwestern Mexico; clinical data were collected, and PCR was used to identify SVG and pathotypes. Antibiotic resistance profiling was performed on DEC strains. 63% of samples were DEC positive, single or combined infections (two (21%) or three strains (1.3%)) of aEPEC (51%), EAEC (10.2%), tEPEC (5.4%), DAEC (4.8%), ETEC (4.1%), EIEC (1.4%), or EHEC (0.7%) were found. Children aged ≤ 12 and 49–60 months and symptoms (e.g., fever and blood) were associated with DEC strains. SVG related to colonization (<i>nleB</i>-EHEC), cytotoxicity (<i>sat</i>-DAEC and <i>espC</i>-tEPEC), and proteolysis (<i>pic</i>-aEPEC) were associated with DECs strains. <i>E</i>. <i>coli</i> phylogroup A was the most frequent, and some pathotypes (aEPEC—A, DAEC–B), and SVG (<i>espC</i>–B2, and <i>sat</i>–D) were associated with the phylogroups. Over 79% of the DEC strains were resistant to antibiotics, and 40% were MDR and XDR, respectively. In conclusion aEPEC was the most prevalent pathotype in children with diarrhea in this region. SVG related to colonization, cytotoxicity, and proteolysis were associated with diarrhea-producing DEC strains, which may play an essential role in the development of diarrhea in children in southwestern Mexico.