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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 -
Biomedical and Environmental Sciences :... Apr 2024
Topics: Animals; Rats; Lycium; Lead; Rhodopseudomonas; Male; Plant Extracts; Lead Poisoning; Rats, Wistar
PubMed: 38727169
DOI: 10.3967/bes2024.050 -
Ecotoxicology and Environmental Safety May 2024Birds are sensitive to heavy metal pollution, and lead (Pb) contamination can negatively affect their liver and gut. Therefore, we used budgerigars to examine liver and...
Birds are sensitive to heavy metal pollution, and lead (Pb) contamination can negatively affect their liver and gut. Therefore, we used budgerigars to examine liver and gut toxicosis caused by Pb exposure in bird, and the possible toxic mechanisms. The findings showed Pb exposure increased liver weight and decreased body weight. Moreover, histopathological and immunofluorescence assay results demonstrated obvious liver damage and cell apoptosis increased in Pb- treated budgerigars. Quantitative polymerase chain reaction (qPCR) results also showed Pb caused an increase in apoptosis by inhibiting the PPAR-γ/PI3K/Akt pathway. The gut microbe analyses indicated Firmicutes, Proteobacteria, and Bacteroidetes were dominant microbial phyla, and Network analysis results shown Arthrobacter, Bradyrhizobium and Alloprevotella as the hubs of Modules I, II, and III, respectively. Phenylpropanoids and polyketides, Organoheterocyclic compounds, Organic oxygen compounds, and Organic nitrogen compounds were dominant metabolite superclasses. Tauroursodeoxycholic acid, taurochenodeoxycholic acid (sodium salt), and 2-[2-(5-bromo-2-pyridyl)diaz-1-enyl]-5-(diethylamino)phenol were significantly enriched in the Pb-treated group. It showed that 41 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues and 183 pathways differed between the Pb-treated and control budgerigars using microbial and metabolomic data. Moreover, orthogonal partial least-squares discrimination analysis (OPLS-DA) based on microbial and metabolite indicated distinct clusters in the Pb-treated and control groups. Additionally, the correlation analysis results indicated that a positive correlation for the Pb-treated and control groups between gut microbiota and metabolomic data, respectively. Furthermore, the microenvironment of the gut and liver were found to affect each other, and this study demonstrated heavy metal especially Pb may pose serious health risks to birds through the "gut-liver axis" too.
PubMed: 38701653
DOI: 10.1016/j.ecoenv.2024.116388 -
Journal of the American Heart... May 2024Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains... (Observational Study)
Observational Study
BACKGROUND
Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear.
METHODS AND RESULTS
This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence.
CONCLUSIONS
Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.
Topics: Humans; Female; Male; Carotid Artery Diseases; Copper; Middle Aged; Risk Factors; Aged; Plaque, Atherosclerotic; Cadmium; Risk Assessment; China; Biomarkers; Asymptomatic Diseases; Lead
PubMed: 38700020
DOI: 10.1161/JAHA.123.033474 -
Cureus Sep 2023Mushroom poisoning, known as mycetism, represents a pressing health concern worldwide. Although the majority of mushroom ingestions are benign, select species like...
Mushroom poisoning, known as mycetism, represents a pressing health concern worldwide. Although the majority of mushroom ingestions are benign, select species like "Amanita phalloides" can induce catastrophic liver damage, culminating in acute liver failure. In this report, we detail a case involving a 35-year-old female who presented to the emergency department exhibiting symptoms of nausea, vomiting, abdominal pain, and palpitations merely six hours post-ingestion of "Amanita phalloides." Accurate identification of the specific mushroom species consumed proves challenging in over 90% of poisoning incidents, underscoring the necessity for clinical vigilance. While many mushroom exposures lead to mild gastrointestinal symptoms, recognizing the potential for severe outcomes is paramount for timely and effective intervention.
PubMed: 38698879
DOI: 10.7759/cureus.45818 -
Frontiers in Veterinary Science 2024The utilization of fauna and fauna-based byproducts in ethnomedicinal usages has been a longstanding human activity, practiced across various cultures worldwide. This...
INTRODUCTION
The utilization of fauna and fauna-based byproducts in ethnomedicinal usages has been a longstanding human activity, practiced across various cultures worldwide. This study focuses on investigating the utilization of animal-based traditional medicine by the people of Pakistan, specifically in the Gujranwala area.
METHODS
Data collection took place from January to September 2019 through interviews with local communities. Ethnomedicinal applications of animal products were analyzed using several indices, including Relative Frequency of Citation (RFC), Relative Popularity Level (RPL), Folk Use Value (FL), and Relative Occurrence Percentage (ROP).
RESULTS
The study identified the use of different body parts of 54 species of animals in treating various diseases and health issues. These include but are not limited to skin infections, sexual problems, pain management (e.g., in the backbone and joints), eyesight issues, immunity enhancement, cold, weakness, burns, smallpox, wounds, poisoning, muscular pain, arthritis, diabetes, fever, epilepsy, allergies, asthma, herpes, ear pain, paralysis, cough, swelling, cancer, bronchitis, girls' maturity, and stomach-related problems. Certain species of fauna were noted by informers with high "frequency of citation" (FC), ranging from 1 to 77. For instance, the black cobra was the most frequently cited animal for eyesight issues (FC = 77), followed by the domestic rabbit for burn treatment (FC = 67), and the Indus Valley spiny-tailed ground lizard for sexual problems (FC = 66). Passer domesticus and were noted to have the highest ROP value of 99.
DISCUSSION
The findings of this study provide valuable preliminary insights for the conservation of fauna in the Gujranwala region of Punjab, Pakistan. Additionally, screening these animals for medicinally active compounds could potentially lead to the development of novel animal-based medications, contributing to both traditional medicine preservation and modern pharmaceutical advancements.
PubMed: 38681848
DOI: 10.3389/fvets.2024.1351693