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CMAJ : Canadian Medical Association... May 2024
Topics: Humans; Lead Poisoning; Male; Female
PubMed: 38802134
DOI: 10.1503/cmaj.231405-f -
Science Advances May 2024DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, topoisomerase I forms a transient intermediate, topoisomerase I-DNA cleavage...
DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, topoisomerase I forms a transient intermediate, topoisomerase I-DNA cleavage complex (Top1cc) to allow strand rotation and duplex relaxation, which can lead to elevated levels of DNA-RNA hybrids and micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data of Top1cc-triggered hybrids and DNA double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid levels with different mechanisms. DSBs are at highly transcribed genes in early replicating initiation zones and overlap with hybrids downstream of accumulated RNA polymerase II (RNAPII) at gene 5'-ends. A transcription factor IIS mutant impairing transcription elongation further increased RNAPII accumulation likely due to backtracking. Moreover, Top1ccs can trigger micronuclei when occurring during late G or early/mid S, but not during late S. As micronuclei and transcription-replication conflicts are attenuated by transcription factor IIS, our results support a role of RNAPII arrest in Top1cc-induced transcription-replication conflicts leading to DSBs and micronuclei.
Topics: DNA Topoisomerases, Type I; Genomic Instability; Humans; R-Loop Structures; DNA Breaks, Double-Stranded; DNA Replication; RNA Polymerase II; Transcription, Genetic
PubMed: 38787953
DOI: 10.1126/sciadv.adm8196 -
Scientific Reports May 2024Psoriasis, characterized as a chronic relapsing disease with a protracted course, often drives patients to seek relief through Chinese folk remedies (CFR). Nonetheless,...
Psoriasis, characterized as a chronic relapsing disease with a protracted course, often drives patients to seek relief through Chinese folk remedies (CFR). Nonetheless, the complex compositions of these remedies frequently result in unintended adverse effects, notably various types of heavy metal poisoning. Our study involved an exhaustive collection and analysis of clinical data from psoriasis patients who developed heavy metal poisoning due to CFR usage, admitted to Beijing Chao-Yang Hospital from January 2011 to October 2023. Our analysis identified 44 cases of mercury poisoning, 17 of lead poisoning, 21 of arsenic poisoning, and 4 instances of mixed heavy metal poisoning. The folk remedies used ranged from fumigation and inhalation to skin application and oral administration. Distinct pathogenic characteristics were observed in each poisoning type. After treatment with metal chelating agents, all patients experienced a reduction in heavy metal levels in their bodies, accompanied by varying degrees of symptom alleviation. This study underscores the vital necessity of opting for formal, medically approved treatments for psoriasis, thereby avoiding the hazardous consequences of unregulated folk remedies that may lead to severe heavy metal poisoning.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Chelating Agents; Drugs, Chinese Herbal; Heavy Metal Poisoning; Medicine, Chinese Traditional; Metals, Heavy; Psoriasis; Retrospective Studies
PubMed: 38783149
DOI: 10.1038/s41598-024-62653-4 -
Environmental Epigenetics 2024In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment,... (Review)
Review
In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment, contaminating both exposed workers and communities living near agricultural areas and via contaminated foodstuffs. In addition to acute poisoning, chronic exposure to pesticides can lead to molecular changes that are becoming better understood. Therefore, the aim of this study was to assess, through a systematic review of the literature, what epigenetic alterations are associated with pesticide exposure. We performed a systematic review and meta-analysis including case-control, cohort and cross-sectional observational epidemiological studies to verify the epigenetic changes, such as DNA methylation, histone modification and differential microRNA expression, in humans who had been exposed to any type of pesticide. Articles published between the years 2005 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI software. Post-completion, the data of selected articles were extracted and analyzed. Most of the 28 articles included evaluated global DNA methylation levels, and the most commonly reported epigenetic modification in response to pesticide exposure was global DNA hypomethylation. Meta-analysis revealed a significant negative correlation between Alu methylation levels and β-hexachlorocyclohexane, ,-dichlorodiphenyldichloroethane and -dichlorodiphenylethylene levels. In addition, some specific genes were reported to be hypermethylated in promoter regions, such as and , while and were hypomethylated due to pesticide exposure. The expression of microRNAs was also altered in response to pesticides, as miR-223, miR-518d-3p, miR-597, miR-517b and miR-133b that are associated with many human diseases. Therefore, this study provides evidence that pesticide exposure could lead to epigenetic modifications, possibly altering global and gene-specific methylation levels, epigenome-wide methylation and microRNA differential expression.
PubMed: 38779494
DOI: 10.1093/eep/dvae005 -
Heliyon May 2024Nowadays, lead poisoning in children commonly occurs, but lead poisoning caused by the administration of Tibetan medicine is rarely reported. This report describes the...
Nowadays, lead poisoning in children commonly occurs, but lead poisoning caused by the administration of Tibetan medicine is rarely reported. This report describes the diagnosis and management of lead poisoning in a 16-year-old girl presented with abdominal pain, vomiting, and anemia with limb numbness, who had a childhood history of epilepsy and took Tibetan medicine intermittently to control the symptoms. After admission into hospital, Computed tomography showed high-density shadows in the gastrointestinal tract. Video-Electroencephalography showed no signs of seizure. Reflux esophagitis was observed in gastroscopy. And no obvious abnormalities in the colonic mucosa through colonoscopy. Bone marrow smear test showed basophilic stippling in the erythrocytes. The blood and urine lead levels of 626 and 75.9 μg/L, respectively. We therefore considered lead poisoning, and the patient improved after chelation therapy. Due to its atypical clinical manifestations, lead poisoning is easily misdiagnosed. Thus, clinicians should pay more attention to this disease. When abdominal pain, anemia, and neurological symptoms are present, the possibility of lead poisoning should be considered.
PubMed: 38765025
DOI: 10.1016/j.heliyon.2024.e30167 -
Respiratory Research May 2024Paraquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms...
Paraquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms of PQ-induced pulmonary fibrosis and whether pulmonary epithelial cell senescence is involved in the process remain elusive. In this study, PQ-induced pulmonary epithelial cell senescence and Hippo-YAP/TAZ activation were observed in both C57BL/6 mice and human epithelial cells. PQ-induced senescent pulmonary epithelial cells promoted lung fibroblast transformation through secreting senescence-associated secretory phenotype (SASP) factors. Yap/Taz knockdown in mice lungs significantly decreased the expression of downstream profibrotic protein Ctgf and senescent markers p16 and p21, and alleviated PQ-induced pulmonary fibrosis. Interfering YAP/TAZ in senescent human pulmonary epithelial cells resulted in decreased expression of the anti-apoptosis protein survivin and elevated level of apoptosis. In conclusion, our findings reveal a novel mechanism by which the involvement of Hippo-YAP/TAZ activation in pulmonary epithelial cell senescence mediates the pathogenesis of PQ-induced pulmonary fibrosis, thereby offering novel insights and potential targets for the clinical management of PQ poisoning as well as providing the mechanistic insight of the involvement of Yap/Taz activation in cell senescence in pulmonary fibrosis and its related pulmonary disorders. The YIN YANG balance between cell senescence and apoptosis is important to maintain the homeostasis of the lung, the disruption of which will lead to disease.
Topics: Animals; Cellular Senescence; YAP-Signaling Proteins; Humans; Mice, Inbred C57BL; Mice; Pulmonary Fibrosis; Adaptor Proteins, Signal Transducing; Transcription Factors; Paraquat; Male; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Epithelial Cells; Trans-Activators
PubMed: 38762455
DOI: 10.1186/s12931-024-02832-z -
Toxicology Letters May 2024Poisoning with organophosphorus compounds, which can lead to a cholinergic crisis due to the inhibition of acetylcholinesterase and the subsequent accumulation of...
Poisoning with organophosphorus compounds, which can lead to a cholinergic crisis due to the inhibition of acetylcholinesterase and the subsequent accumulation of acetylcholine (ACh) in the synaptic cleft, is a serious problem for which treatment options are currently insufficient. Our approach to broadening the therapeutic spectrum is to use agents that interact directly with desensitized nicotinic acetylcholine receptors (nAChRs) in order to induce functional recovery after ACh overstimulation. Although MB327, one of the most prominent compounds investigated in this context, has already shown positive properties in terms of muscle force recovery, this compound is not suitable for use as a therapeutic agent due to its insufficient potency. By means of in silico studies based on our recently presented allosteric binding pocket at the nAChR, i.e. the MB327-PAM-1 binding site, three promising MB327 analogs with a 4-aminopyridinium ion partial structure (PTM0056, PTM0062, and PTM0063) were identified. In this study, we present the synthesis and biological evaluation of a series of new analogs of the aforementioned compounds with a 4-aminopyridinium ion partial structure (PTM0064-PTM0072), as well as hydroxy-substituted analogs of MB327 (PTMD90-0012 and PTMD90-0015) designed to substitute entropically unfavorable water clusters identified during molecular dynamics simulations. The compounds were characterized in terms of their binding affinity towards the aforementioned binding site by applying the UNC0642 MS Binding Assays and in terms of their muscle force reactivation in rat diaphragm myography. More potent compounds were identified compared to MB327, as some of them showed a higher affinity towards MB327-PAM-1 and also a higher recovery of neuromuscular transmission at lower compound concentrations. To improve the treatment of organophosphate poisoning, direct targeting of nAChRs with appropriate compounds is a key step, and this study is an important contribution to this research.
PubMed: 38759939
DOI: 10.1016/j.toxlet.2024.05.011 -
Environmental Pollution (Barking, Essex... May 2024Numerous edible mushrooms accumulate Potentially Toxic Elements (PTE), such as cadmium, mercury, and lead, within their sporocarps. This accumulation poses a potential...
Numerous edible mushrooms accumulate Potentially Toxic Elements (PTE), such as cadmium, mercury, and lead, within their sporocarps. This accumulation poses a potential risk of poisoning for humans and is influenced by factors such as the mushroom species, type of element, and the level of industrialization in the region. In our study, we investigated how soil and tree stand characteristics, including C/N ratio, pH, tree diversity, canopy cover, and the proportion of deciduous trees, influence PTE concentration in mushrooms. We collected edible mushrooms from 20 plots situated in the Białowieża Primeval Forest, one of Europe's best-preserved lowland forests. Plots varied in terms of tree species composition, with other factors minimized. We used ICP-MS (Inductively Coupled Plasma - Mass Spectrometry) technique to analyze the concentration of eight PTE (Ag, As, Cd, Ni, Pb, Sb, Sr, Tl) in eight edible mushroom species (M.procera, L.perlatum, R. butyracea, R.cyanoxantha, R.heterophylla, L.vellereus, A.mellea, and Xerocomellus chrysenteron). Our research revealed that the presence of the effect of specific factors on concentration of PTE and its direction depends on mushroom species and type of PTE. The proportion of deciduous tree species and pH of the topsoil layer emerged as the most influential factors affecting PTE concentration in mushroom samples. Tree species richness in the canopy layer did not affect PTE concentration in mushrooms, except for the concentration of Pb in X. chrysenteron. We observed a consistent profile of PTE concentration in mushrooms with similar ecological roles (ectomycorrhizal, saprotrophic, parasite mushrooms) and from comparable phylogenetic affinities.
PubMed: 38754693
DOI: 10.1016/j.envpol.2024.124152 -
Nature Communications May 2024Lead (Pb) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have...
Lead (Pb) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb poisoning.
PubMed: 38744833
DOI: 10.1038/s41467-024-47938-6 -
Nanomaterials (Basel, Switzerland) May 2024Heavy metal poisoning has a life-threatening impact on the human body to aquatic ecosystems. This necessitates designing a convenient green methodology for the...
Heavy metal poisoning has a life-threatening impact on the human body to aquatic ecosystems. This necessitates designing a convenient green methodology for the fabrication of an electrochemical sensor that can detect heavy metal ions efficiently. In this study, boron (B) and nitrogen (N) co-doped laser-induced porous graphene (LIG) nanostructured electrodes were fabricated using a direct laser writing technique. The fabricated electrodes were utilised for the individual and simultaneous electrochemical detection of lead (Pb) and cadmium (Cd) ions using a square wave voltammetry technique (SWV). The synergistic effect of B and N co-doping results in an improved sensing performance of the electrode with better sensitivity of 0.725 µA/µM for Pb and 0.661 µA/µM for Cd ions, respectively. Moreover, the sensing electrode shows a low limit of detection of 0.21 µM and 0.25 µM for Pb and Cd ions, with wide linear ranges from 8.0 to 80 µM for Pb and Cd ions and high linearity of R = 0.99 in case of simultaneous detection. This rapid and facile method of fabricating heteroatom-doped porous graphene opens a new avenue in electrochemical sensing studies to detect various hazardous metal ions.
PubMed: 38727400
DOI: 10.3390/nano14090806