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DOAJ Open Access 2026
Research progress on relationship and mechanism between shift work and vascular aging

Zeyu YANG, Yu ZHANG, Xiaohui LU

Shift work, as a form of non-conventional work schedule, significantly increases the risk of vascular aging and related diseases due to circadian rhythm disruption, sleep disturbances, and unhealthy lifestyle behaviors. This review systematically summarized the mechanisms and epidemiological evidence linking shift work to vascular aging. Available studies indicated that shift work disrupts the rhythmic expression of core circadian clock genes (e.g., BMAL1, CLOCK, PER, CRY), leading to dysregulated glucose and lipid metabolism, enhanced oxidative stress, chronic inflammation, and altered diurnal blood pressure patterns, thereby directly impairing endothelial function and accelerating arterial stiffness. Sleep deprivation and fragmentation further reduce nitric oxide bioavailability and promote endothelin-1 secretion, exacerbating vascular constriction and inflammatory responses. Existing epidemiological data show that shift workers exhibit higher prevalence of hypertension, metabolic syndrome, and atherosclerosis compared with non-shift workers, accompanied by abnormal vascular function indicators such as pulse wave velocity and carotid intima-media thickness. Additionally, unhealthy dietary habits, psychological stress, and sedentary behavior in shift workers synergistically contribute to vascular aging. This review aims to provide a theoretical basis for the pathological link between shift work and vascular aging and to inform public health policy formulation and occupational health management.

Medicine (General), Toxicology. Poisons
DOAJ Open Access 2026
MicroRNA-mediated changes contributing to benzo[a]pyrene toxicity in a 3D respiratory model for asthma

Reese M. Valdez, Yvonne Chang, Jamie M. Pennington et al.

There is increased emphasis on understanding how non-chemical stressors that contribute to inflammation in the lung may influence adverse health outcomes after chemical exposures. Prior studies in an in vitro respiratory model of type 2 asthmatic inflammation found cells from the asthmatic phenotype respond uniquely to benzo[a]pyrene (BAP) treatment compared to normal cells across multiple endpoints related to mucus production, goblet cell hyperplasia, mucociliary dysfunction and airway remodeling. To further understand how cellular response to BAP is regulated in a model of inflammation-based disease, this study examines changes in miRNA and mRNA regulation following BAP exposure in primary human bronchial epithelial cells (HBECs) cultured at the air–liquid interface with normal and interlukin-13 (IL-13) induced asthmatic phenotypes. Primary 3D HBECs differentiated in the presence and absence of 10 ng/mL IL-13 were treated on day 25 with 158 µM BAP for 48 h. Differentially expressed (q < 0.01) miRNA and mRNA were analyzed to predict miRNA target interactions and assess the functional consequences of miRNAs in each phenotype. While BAP-treated HBEC with the IL-13 asthmatic phenotype had a similar number of differentially expressed miRNA (93 up- and 100 down-regulated) compared to BAP-treated normal HBEC (93 up- and 94 down-regulated), IL-13 HBEC treated with BAP were shown to have unique enrichment of miRNA targets involved in up-regulation of cell cycle processes and down-regulation of processes related to NOTCH, WNT, and Hedgehog signaling. These data are the first to provide insight into the role of miRNAs as regulators of chemical toxicity in a respiratory model of inflammation-based disease.

Toxicology. Poisons
DOAJ Open Access 2025
Neurometabolomic impacts of wood smoke and protective benefits of anti-aging therapeutics in aged female C57BL/6J mice

David Scieszka, Jonathan Hulse, Haiwei Gu et al.

Abstract Background Wildland fires in the United States have increased in frequency and scale over the past 30 years exposing millions of people to hazardous air pollutants. Among others, aging individuals are particularly vulnerable to the effects of wildfire smoke. In this study, we assessed the neurobiological impacts of wood smoke (WS) on aged mice and the potential of anti-aging therapeutics to mitigate these impacts. Methods Female C57BL/6 J mice, aged 18 months, were divided into 10 groups and exposed to either filtered air (FA; 5 groups) or biomass derived WS (5 groups) for 4 h/day, every other day, for 14 days (7 exposures total) with an average particulate matter (PM) concentration of 448 µg/m3 per exposure. One FA control group and one WS exposed group were euthanized 24 h after the last exposure. The remaining 8 groups (4 FA and 4 WS exposed) were treated with either vehicle control, resveratrol and nicotinamide mononucleotide (RNMN), dasatinib and quercetin (DQ), or both RNMN and DQ (RNDQ) for 10 weeks. Results A significant reduction in NAD + within the prefrontal cortex was observed following the 14-day exposure to WS along with a reduction in serotonin. Serotonin reductions were observed up to 10 weeks post-exposure and co-occurred with neuroinflammation and behavioral alterations, including increased immobility in a forced swim test. RNMN conferred the greatest mitigating effect after WS exposure, while RNDQ treatment resulted in an upregulation of markers associated with aging in the brain. While the metabolic shift in the PFC following WS exposure was relatively modest, mice exposed to FA and vehicle control (10 weeks of natural aging) exhibited the greatest metabolic shift, including perturbed nicotinamide metabolism. Conclusion Taken together, these findings highlight that subacute (14-day) exposure to WS results in persistent neurometabolomic and behavioral alterations in an aged mouse model and that intervention with RNMN may be a useful strategy to mitigate the adverse neurological outcomes observed. Further studies are needed to assess the specific impact of either resveratrol or NMN in isolation and to fully elucidate age-specific, as well as sex- and species-determinant, WS exposure response pathways.

Toxicology. Poisons, Industrial hygiene. Industrial welfare
DOAJ Open Access 2025
A survey to evaluate animal methods bias experienced by India-based researchers in the peer review of manuscripts and grant applications

Surat Parvatam, Karishma Kaushik, Kasturi Mahadik et al.

While peer review during manuscript or grant application forms the cornerstone of scientific evaluation and assessment, this process is also prone to biases and confounding. Animal methods bias is a specific form of peer review bias where a preference for animal-based research methods or a lack of expertise in nonanimal-based methods undermines the quality and fairness of assessments of nonanimal studies. In this study, we conducted a survey to assess the challenges and experiences of researchers in India to publish peer-reviewed publications and apply for grants based on projects using nonanimal methods. A cross-sectional survey with 19 questions was completed by 186 respondents working in various biological fields in India. Decision logic was used to route respondents through the survey, which led to varying number of responses per question. Fifty-six per cent of respondents (39 out of 70) said they have been asked by manuscript reviewers to add animal experiments to their otherwise nonanimal-based studies. Respondents reported complying to 24 % of these requests on average. Respondents indicated the primary impacts of requests for additional experiments were publishing in lower impact factor journals and manuscript rejection. In addition, 57 % (47 of 83 respondents) felt that the lack of animal experiments in their grant proposal negatively influenced its evaluation. Respondents were also asked about key factors influencing their use of animal and nonanimal methods, which revealed that some perceived animal methods as necessary to validate nonanimal methods and as more reliable for mimicking biological complexity, while others perceived nonanimal methods as more physiologically relevant and practically advantageous. This survey provides preliminary evidence of animal methods bias experiences during publishing and funding peer review faced by Indian researchers.

Toxicology. Poisons
DOAJ Open Access 2025
<i>Avena sativa</i> as a Multifunctional Tool for Phytoremediation and Bioenergy Production in Sulfentrazone Contaminated Soils

Caique Menezes de Abreu, Guilherme Henrique Fernandes Carneiro, Márcia Regina da Costa et al.

Phytoremediation using <i>Avena sativa</i> offers a sustainable strategy for mitigating sulfentrazone contamination while integrating bioenergy production. This study proposes an analysis of the bioenergy potential and the microbial metagenomic profile associated with <i>Avena sativa</i> in the presence and absence of sulfentrazone, aiming at the synergistic bioprospecting of microbial communities capable of biodegradation and remediation of contaminated environments. Using a randomized block design, we evaluated the bioenergy potential and rhizospheric microbial dynamics of <i>A. sativa</i> in soils with and without sulfentrazone (600 g ha<sup>−1</sup>). Herbicide residues were quantified via UHPLC-MS/MS, and metagenomic profiles were obtained through 16S rRNA gene and ITS region sequencing to assess shifts in rhizospheric microbiota. Microbial diversity was analyzed using the Shannon and Gini–Simpson Indices, complemented by Principal Component Analysis (PCA). Bioenergy yields (biogas and ethanol) were estimated based on plant biomass. Over 80 days, the cultivation of <i>A. sativa</i> promoted a 19.7% dissipation of sulfentrazone, associated with rhizospheric enrichment of plant growth-promoting taxa (<i>Bradyrhizobium</i>, <i>Rhodococcus</i>, and <i>Trichoderma</i>), which increased by 68% compared to uncontaminated soils. Contaminated soils exhibited reduced microbial diversity (Gini–Simpson Index = 0.7), with a predominance of <i>Actinobacteria</i> and <i>Ascomycota</i>, suggesting adaptive specialization. Despite herbicide-induced stress (39.3% reduction in plant height and 60% reduction in grain yield), the biomass demonstrated considerable bioenergy potential: 340.6 m<sup>3</sup> ha<sup>−1</sup> of biogas and 284.4 L ha<sup>−1</sup> of ethanol. The findings highlight the dual role of <i>A. sativa</i> in soil rehabilitation and renewable energy systems, supported by plant–microbe synergies. Scalability challenges and regulatory gaps in ecotoxicological assessments were identified, reinforcing the need to optimize microbial consortia and implement region-specific management strategies. These results support the integration of phytoremediation into circular bioeconomy models, balancing ecological recovery with agricultural productivity. Future research should focus on microbial genetic pathways, field-scale validation, and the development of regulatory frameworks to advance this green technology in global soil remediation efforts.

Therapeutics. Pharmacology, Toxicology. Poisons
DOAJ Open Access 2025
Multi-omics-based decoding of circulating biomarkers in amyotrophic lateral sclerosis and risks in environmental toxins

Lei Xu, Bin Huang, Yaqiu Zhou et al.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the interplay of genetic and environmental factors, and currently, there there is a lack of effective diagnostic or therapeutic strategies available. This study aims to identify circulating biomarkers for ALS and investigate their interactions with environmental toxins. Methods This research utilizes plasma proteomic genome-wide association study (GWAS) data and whole blood transcriptomic data from ALS patients to screen for potential circulating biomarkers through Mendelian randomization (MR). Subsequently, functional enrichment analysis and immune infiltration analysis were performed. An integrated machine learning approach will be used to construct a diagnostic model, with hub genes selected based on SHAP values. The model’s performance will be validated using receiver operating characteristic (ROC) curves, nomogram, and decision curve analysis (DCA). Finally, reverse network toxicology will be used to explore the interaction mechanisms between hub genes and environmental toxins. Results Based on a MR analysis of plasma proteomics, we identified 68 plasma proteins significantly associated with the risk of ALS. By integrating differentially expressed genes (DEGs) from whole blood transcriptomics (1,116 DEGs), we selected four potential circulating biomarkers: FCRL3, HTATIP2, RNASE6, and SF3B4. Functional enrichment analysis indicated that the pathogenesis of ALS is closely related to autophagy, apoptosis, the endoplasmic reticulum unfolded protein response, and the NF-κB signaling pathway. Immune infiltration analysis revealed a disruption of the immune microenvironment mediated by T cells/myeloid cells in ALS patients. Validation through 113 machine learning algorithms showed that the random forest model exhibited the best diagnostic performance (AUC = 0.786), while SHAP analysis confirmed the contribution ranking of hub biomarkers: RNASE6 > FCRL3 > HTATIP2 > SF3B4. Further validation of their diagnostic value was performed using ROC curves, nomograms, and DCA. Environmental toxins analysis revealed that substances such as benzo(a)pyrene exhibit significant neurotoxicity, and molecular docking confirmed that they can interfere with the function of hub biomarkers through strong binding (∆G < -5 kcal·mol⁻¹), suggesting potential environmental pathogenic mechanisms in ALS. Conclusions This study not only highlights the value of FCRL3, HTATIP2, RNASE6, and SF3B4 as potential diagnostic biomarkers and therapeutic targets for ALS but also provides new evidence for the involvement of environmental toxins, particularly benzo(a)pyrene, in the pathogenesis of ALS through gene-environment interactions.

Therapeutics. Pharmacology, Toxicology. Poisons
DOAJ Open Access 2024
Application of single-cell sequencing technology to the study of embryonic developmental toxicity of emerging contaminants: Progress and perspectives

Weizhao CAO, Yunhui ZHANG

Emerging pollutants are a class of environmental chemicals characterized by bioaccumulation, environmental persistence, and high toxicity. Their long-term accumulation poses severe threats to the environment and human health. In recent years, single-cell RNA sequencing (scRNA-seq) technology has enabled the analysis of transcriptomes at the single-cell level, revealing cellular heterogeneity and the complexity of intercellular communication. In toxicological studies, scRNA-seq technology has been applied to identify the responses of different cell types to pollutants and to elucidate the mechanisms of pollutant action during embryonic development, providing novel perspectives on the toxicity mechanisms of emerging pollutants. This paper reviewed the classification and characteristics of single-cell sequencing technologies and their applications in investigating the developmental toxicity of emerging pollutants, including perfluorinated and polyfluorinated alkyl substances (PFAS), antibiotics, microplastics, phthalates, and bisphenols. It also discussed the limitations of current studies and proposed future research directions. Through methods such as cellular heterogeneity analysis and pseudotemporal chronological analysis, single-cell sequencing can explore and validate the specific toxicity mechanisms of emerging pollutants in embryonic development. However, challenges remain, including dataset bias, batch effects, and developmental differences between humans and model organisms. Future research should focus on optimizing data analysis methods, integrating multi-omics sequencing data, and exploring the use of human organoid models in toxicological studies. Such efforts will contribute to a more comprehensive understanding of the toxicity mechanisms and long-term health impacts of emerging pollutants, providing a theoretical basis for their stringent regulation and control.

Medicine (General), Toxicology. Poisons
DOAJ Open Access 2023
Transcriptome analysis of the spider Phonotimpus pennimani reveals novel toxin transcripts

Jonathan David Baza-Moreno, Leticia Vega-Alvarado, Guillermo Ibarra-Núñez et al.

Abstract Background: Phonotimpus pennimani (Araneae, Phrurolithidae) is a small-sized (3-5 mm) spider endemic to the Tacaná volcano in Chiapas, Mexico, where it is found in soil litter of cloud forests and coffee plantations. Its venom composition has so far not been investigated, partly because it is not a species of medical significance. However, it does have an important impact on the arthropod populations of its natural habitat. Methods: Specimens were collected in Southeastern Mexico (Chiapas) and identified taxonomically by morphological characteristics. A partial sequence from the mitochondrial gene coxI was amplified. Sequencing on the Illumina platform of a transcriptome library constructed from 12 adult specimens revealed 25 toxin or toxin-like genes. Transcripts were validated (RT-qPCR) by assessing the differential expression of the toxin-like PpenTox1 transcript and normalising with housekeeping genes. Results: Analysis of the coxI-gene revealed a similarity to other species of the family Phrurolithidae. Transcriptome analysis also revealed similarity with venom components of species from the families Ctenidae, Lycosidae, and Sicariidae. Expression of the toxin-like PpenTox1 gene was different for each developmental stage (juvenile or adult) and also for both sexes (female or male). Additionally, a partial sequence was obtained for the toxin-like PpenTox1 from DNA. Conclusion: Data from the amplification of the mitochondrial coxI gene confirmed that P. pennimani belongs to the family Phrurolithidae. New genes and transcripts coding for venom components were identified.

Arctic medicine. Tropical medicine, Toxicology. Poisons
DOAJ Open Access 2023
Analysis of C-reactive protein level in SARS-CoV-2 patients and its role in predicting the severity of SARS-CoV-2 infection

Rozina Arshi Khan, Qursheed Sultana, Pendru Raghunath et al.

Introduction: Corona Virus Disease-19 (COVID-19) pandemic is a public health emergency due to the spread of 2019 novel Corona Virus (2019-nCoV), also called as Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). Analysis of CRP along with various other haematological parameters serves as a predictor of infection and inflammation. Aims and objectives: The aim of the study was to study the CRP level in SARS-CoV-2 patients and its role in predicting the severity of infection. Materials and Methods: As many as 768 patients were included in this study. Serum samples were analysed for CRP levels by Quantitative CRP test, based on the principle of Latex turbidimetry. CRP values equal to or greater than 6mg/L were considered as abnormal. Results: Out of 768 serum samples tested, 337 (43.8%) samples showed abnormal values. Out of which 255 (75.7%) were male patients and 82(24.3%) were female patients. A total of 42.4% patients had increased CRP values that belonged to the age group 41-60 years followed by 29% patients that belonged to the age group of 61-80 years. In the age group of 61-80 years 67/98 (68%) patients deteriorated during hospitalization and required mechanical ventilation and the mortality rate was 88% among patients on mechanical ventilation. Conclusion: Our study suggested that CRP testing may be useful as an earlier indicator for severe illness and those presenting with marked increase of > 45.6 mg/L should be paid more attention. Male preponderance was detected and elderly patients revealed abnormal values of CRP as compared to young and middle-aged patients.

Therapeutics. Pharmacology, Toxicology. Poisons
DOAJ Open Access 2023
Therapeutic capability of selected medicinal plants' bioactive constituents against the mutant ovarian TP53 gene; a computational approach

Kayode Yomi Raheem, Fawehinmi Praise Ibukunoluwa, Solomon Ayodele Olorundare et al.

A mutant P53 protein plays such a crucial role in ovarian cancer, and natural compounds have been known to be effective in treating cancer. The current study was conducted to discover new mutant P53 modulators in plants used for medicinal purposes. The mutant p53 3D structure was built using homology modeling, while its active binding domain was predicted using Findsitecom2.0. Docking studies were conducted with ligands derived from bioactive components of seven different plants and mutant p53 binding sites. Autodocking programs, including Discovery Studio and PyRx, were used to obtain the docking protein and its intricate visual representation. Gemcitabine and thiotepa were the reference drugs. Acute RAT toxicity and Pharmacokinetic properties were utilized in Gusar and SWISSADME, respectively, to narrow down the hit compounds to those with the highest binding affinities. Using the density functional theory (DFT) method, the electronic properties of the bioactive constituents were determined. 15 of the 50 bioactive phytochemicals displayed superior mutant p53 binding energies compared to Gemcitabine and Thioteba (−5.4 and −3.5 binding scores, respectively). Considering acute toxicity predictions and pharmacokinetics, 10-hydroxycamptothecin, irinotecan, morusin, and rubitecan were the four major compounds with low toxicity. DFT calculations uncovered regions susceptible to nucleophilic and electrophilic assaults. The study sought to identify potential drug candidates for modulating mutant P53 in ovarian cancer treatment.

Toxicology. Poisons, Biotechnology
DOAJ Open Access 2022
Light and heavy ferritin chain expression in the liver and kidneys of Wistar rats: aging, sex differences, and impact of gonadectomy

Vulinović Mirela Pavić, Turčić Petra, Micek Vedran et al.

Ferritin is the main intracellular storage of iron. Animal studies show that female liver and kidney express more ferritin and accumulate more iron than male. However, no study so far has investigated sex and age differences in light (FtL) and heavy (FtH) ferritin chain expression. To address this, we relied on specific antibodies and immunochemical methods to analyse the expression of both ferritin chains in the liver and kidney of 3-month and 2-year-old male and female Wistar rats. To see how sex hormones may affect expression we also studied adult animals gonadectomised at the age of 10 weeks. FtL and FtH were more expressed in both organs of female rats, while gonadectomy increased the expression in males and decreased it in females, which suggests that it is stimulated by female and inhibited by male steroid hormones. Normal kidney ferritin distribution and change with aging warrant more attention in studies of (patho) physiological and toxicological processes.

Toxicology. Poisons
DOAJ Open Access 2022
A questionnaire based cross sectional survey of attitude and practice of complementary and alternative medicine in medical practitioners

Pradnya Deolekar, Kavitha Dongerkery, Pramila Yadav et al.

Background: Complementary and alternative medicine (CAM) has been practised in India since many years. People unsatisfied with conventional medicine often turn to unconventional alternatives. Aim is to appraise the extent of use of CAM amongst doctors and to examine their perception, attitude and practice towards CAM. Methods: This study was conducted among 105 doctors. A predesigned validated, questionnaire was used to evaluate the attitude and practice. Of 150 physicians who were given questionnaire to participate in the survey, 105 (70%) responded. Results: 22 (20.95%) were specialists and 83 (79.04%) General physicians. 79 (75.23%) Physician’s considered that CAM has a beneficial role and 69 (65.71%) advised use of CAM in patients but only 25.71% would refer patients to CAM practitioners for treatment of an ailment. Of the total 105 physicians 31.42%. General practitioners suggested Ayurveda therapy as compared to 10.47% specialists. 36% of the patients preferred Ayurveda as opined by the physician. Homeopathy was recommended by 35% followed by herbal medicine 32% and 30% naturopathy. However, physicians’ responses on most of the CAM therapies i.e. Ayurveda, homeopathy, naturopathy, herbal medicine etc. was found to be statistically not significant. Conclusions: In the future, physicians can more readily used CAM. Because evidence for the effectiveness of CAM remains sparse, more research is needed for the prudent use of CAM. An education and training system for potential CAM providers remains to be developed.

Therapeutics. Pharmacology, Toxicology. Poisons
DOAJ Open Access 2021
Allisartan ameliorates vascular remodeling through regulation of voltage-gated potassium channels in hypertensive rats

Xiaoqin Zhang, Ziying Zhao, Chunfang Xu et al.

Abstract Background The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats. Methods The study included a total of 47 Sprague Dawley (SD) rats. The animals were randomized to sham operation (n = 14), untreated hypertensive control group (n = 18) and allisartan treatment group (n = 15). Using renal artery stenosis, hypertension was induced in animals. Single dose of allisartan was administered intra-gastrically to animals in the allisartan treatment group and match placebo in the other 2 groups. Wire myography was used to measure the muscle tension in isolated mesenteric arteries from the animals. Real-time polymerase chain reaction was used to quantify the expression of Kv7 channel mRNA subunits. Results After 4 weeks of treatment, a significant decrease in mean arterial, systolic and diastolic blood pressure (SBP and DBP) was observed in allisartan treatment group compared to hypertension control group. The median arterial wall thickness and area/diameter ratio reduced significantly in treatment group compared to untreated hypertension group (P < 0.05). Wire myography demonstrated increased relaxation of mesenteric artery with increase in concentration of ML213. A significant up-regulation in the expression of all Kv7 mRNA subunits was observed in allisartan group compared to untreated hypertension group. Conclusions From the results, allisartan was found to lower BP and preserve vascular remodeling through Kv7 channels.

Therapeutics. Pharmacology, Toxicology. Poisons
DOAJ Open Access 2021
Evaluation of efficacy of low-intensity laser therapy on acceleration of orthodontic tooth movement by measuring IL-6 and TNF- α levels in GCF- A randomized clinical controlled trial

Amir S. Shaikh, Sumaiya Pathan, Shakeel Galagali et al.

Aims and Objectives: There is a profuse tendency for researches to focus on accelerating methods for tooth movement due to the huge demand from adults for a shorter orthodontic treatment time. Photobiomodulation is an emerging area of science that has clinical applications in number of human biological processes. Low-Intensity laser therapy (LILT) has been discussed in many fields of dentistry and hence this study was undertaken to evaluate the efficacy of Low Intensity Diode Laser to accelerate orthodontic tooth movement and correlating the IL6 and TNF α - levels in gingival crevicular fluid. Materials and Methods: Twenty patients aged from 15 to 22 years were randomly selected and among these patients, ten patients were allotted for experimental and ten patients served as controlled groups by flip coin method. Treatment was initiated by bonding fixed appliances in both the arches. The experimental group was treated with LILT using Diode Laser. GCF was collected by intrasulcular technique at different period of intervals and subjected to laboratory assessment. Results: There was statistical significance in the rate of tooth movement in the experimental group (LILT). Increased levels of TNF-α and IL-6 were also observed in GCF samples of experimental group as compared with the control group. Conclusion: Application of low-level laser therapy in adjunctive to orthodontic forces accelerated orthodontic tooth movement along with increased the levels of TNF-α and IL-6 in gingival crevicular fluid.

Therapeutics. Pharmacology, Toxicology. Poisons
DOAJ Open Access 2020
Cytotoxic and anticancer properties of the Malaysian mangrove pit viper (Trimeresurus purpureomaculatus) venom and its disintegrin (purpureomaculin)

Choo Hock Tan, Jia Lee Liew, Suerialoasan Navanesan et al.

Abstract Background: The Asiatic pit vipers from the Trimeresurus complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of Trimeresurus spp.; however, hold great potential for the development of peptide-based anticancer drugs. Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue. Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study. Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.

Arctic medicine. Tropical medicine, Toxicology. Poisons
DOAJ Open Access 2017
A review on the Scorpaena plumieri fish venom and its bioactive compounds

Fabiana V. Campos, Thiago N. Menezes, Pedro F. Malacarne et al.

Abstract The most poisonous fish species found along the Brazilian coast is the spotted scorpionfish Scorpaena plumieri. Though hardly ever life-threatening to humans, envenomation by S. plumieri can be quite hazardous, provoking extreme pain and imposing significant socioeconomic costs, as the victims may require days to weeks to recover from their injuries. In this review we will walk the reader through the biological features that distinguish this species as well as the current epidemiological knowledge related to the envenomation and its consequences. But above all, we will discuss the challenges involved in the biochemical characterization of the S. plumieri venom and its compounds, focusing then on the successful isolation and pharmacological analysis of some of the bioactive molecules responsible for the effects observed upon envenomation as well as on experimental models. Despite the achievement of considerable progress, much remains to be done, particularly in relation to the non-proteinaceous components of the venom. Therefore, further studies are necessary in order to provide a more complete picture of the venom’s chemical composition and physiological effects. Given that fish venoms remain considerably less studied when compared to terrestrial venoms, the exploration of their full potential opens a myriad of possibilities for the development of new drug leads and tools for elucidating the complex physiological processes.

Arctic medicine. Tropical medicine, Toxicology. Poisons
DOAJ Open Access 2011
In vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom

A Jalali, M H Pipelzadeh, R Seyedian et al.

The available Razi Institute antivenom is still, empirically, used by intramuscular (IM) administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus). The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH) following H. lepturus sting. Simultaneous intramuscular administration of 10 &#956;L and 100 &#956;L of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC) count and hemoglobin were observed. Immediate intramuscular administration of 10 &#956;L of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.

Arctic medicine. Tropical medicine, Toxicology. Poisons
DOAJ Open Access 2008
Field evaluation of a new particle concentrator- electrostatic precipitator system for measuring chemical and toxicological properties of particulate matter

Pakbin Payam, Sillanpää Markus, Ning Zhi et al.

<p>Abstract</p> <p>Background</p> <p>A newly designed electrostatic precipitator (ESP) in tandem with Versatile Aerosol Concentration Enrichment System (VACES) was developed by the University of Southern California to collect ambient aerosols on substrates appropriate for chemical and toxicological analysis. The laboratory evaluation of this sampler is described in a previous paper. The main objective of this study was to evaluate the performance of the new VACES-ESP system in the field by comparing the chemical characteristics of the PM collected in the ESP to those of reference samplers operating in parallel.</p> <p>Results</p> <p>The field campaign was carried out in the period from August, 2007 to March, 2008 in a typical urban environment near downtown Los Angeles. Each sampling set was restricted to 2–3 hours to minimize possible sampling artifacts in the ESP. The results showed that particle penetration increases and ozone concentration decreases with increasing sampling flow rate, with highest particle penetration observed between 100 nm and 300 nm. A reference filter sampler was deployed in parallel to the ESP to collect concentration-enriched aerosols, and a MOUDI sampler was used to collect ambient aerosols. Chemical analysis results showed very good agreement between the ESP and MOUDI samplers in the concentrations of trace elements and inorganic ions. The overall organic compound content of PM collected by the ESP, including polycyclic aromatic hydrocarbons (PAHs), hopanes, steranes, and alkanes, was in good agreement with that of the reference sampler, with an average ESP -to -reference concentration ratio of 1.07 (± 0.38). While majority of organic compound ratios were close to 1, some of the semi-volatile organic species had slightly deviated ratios from 1, indicating the possibility of some sampling artifacts in the ESP due to reactions of PM with ozone and radicals generated from corona discharge, although positive and negative sampling artifacts in the reference filter sampler cannot be ruled out.</p> <p>Conclusion</p> <p>The very good overall agreement between ESP and reference samplers makes it an attractive alternative to filters and biosamplers for chemical and toxicological evaluation of PM properties, including the possibility of conducting direct in vitro cell exposures. Moreover, the concentration enrichment of ambient aerosols by the VACES allows for short-term exposure studies, which preserve cell viability and enable studies to PM generated from specific sources and-or formation mechanisms in the atmosphere.</p>

Toxicology. Poisons, Industrial hygiene. Industrial welfare

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