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GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity.ACS Omega Jun 2024Tobacco smoking is a major risk factor for disease development, with the user inhaling various chemicals known to be toxic. However, many of these chemicals are absent...
Tobacco smoking is a major risk factor for disease development, with the user inhaling various chemicals known to be toxic. However, many of these chemicals are absent before tobacco is "burned". Similar, detailed data have only more recently being reported for the e-cigarette with regards to chemicals present before and after the e-liquid is "vaped." Here, zebrafish were dosed with vaped e-liquids, while C57-BL/6J mice were vaped using nose-cone only administration. Preliminary assessments were made using e-liquids and GC/HRMS to identify chemical signatures that differ between unvaped/vaped and flavored/unflavored samples. Oxidative stress and inflammatory immune cell response assays were then performed using our in vivo models. Chemical signatures differed, e.g., between unvaped/vaped samples and also between unflavored/flavored e-liquids, with known chemical irritants upregulated in vaped and unvaped flavored e-liquids compared with unflavored e-liquids. However, when possible respiratory irritants were evaluated, these agents were predominantly present in only the vaped e-liquid. Both oxidative stress and inflammatory responses were induced by a menthol-flavored but not a tobacco-flavored e-liquid. Thus, chemical signatures differ between unvaped versus vaped e-liquid samples and also between unflavored versus flavored e-liquids. These flavors also likely play a significant role in the variability of e-liquid characteristics, e.g., pro-inflammatory and/or cytotoxic responses.
PubMed: 38911720
DOI: 10.1021/acsomega.4c03416 -
Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.Science Advances Jun 2024Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold...
Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold sensing and pain perception. Clinical trials targeting TRPM8 have faced repeated setbacks predominantly due to the knowledge gap in unraveling the molecular underpinnings governing polymodal activation. A better understanding of the molecular foundations between the TRPM8 activation modes may aid the development of mode-specific, thermal-neutral therapies. Ancestral sequence reconstruction was used to explore the origins of TRPM8 activation modes. By resurrecting key TRPM8 nodes along the human evolutionary trajectory, we gained valuable insights into the trafficking, stability, and function of these ancestral forms. Notably, this approach unveiled the differential emergence of cold and menthol sensitivity over evolutionary time, providing a fresh perspective on complex polymodal behavior. These studies provide a paradigm for understanding polymodal behavior in TRPM8 and other proteins with the potential to enhance our understanding of sensory receptor biology and pave the way for innovative therapeutic interventions.
Topics: TRPM Cation Channels; Humans; Menthol; Cold Temperature; Evolution, Molecular; Phylogeny; Thermosensing
PubMed: 38905339
DOI: 10.1126/sciadv.adm9228 -
Molecules (Basel, Switzerland) Jun 2024Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and "cooling agents" such as menthol and icilin, which induce a cold...
Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and "cooling agents" such as menthol and icilin, which induce a cold sensation. The stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigate the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that the inhibition of phosphatidylinositol 4-phosphate 5 kinase α (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuates TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that the pharmacological inhibition of the βγ subunits impairs TRPM8 signaling. In addition, genetic studies show that TRPM8 requires an activated Gα subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers the activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identify the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signaling cascade. In summary, with PIP5K, Gq subunits, and c-Jun, we identified key molecules in TRPM8-induced signaling from the plasma membrane to the nucleus.
Topics: TRPM Cation Channels; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Signal Transduction; Phosphotransferases (Alcohol Group Acceptor); Transcription Factor AP-1; HEK293 Cells; Proto-Oncogene Proteins c-jun; Animals
PubMed: 38893478
DOI: 10.3390/molecules29112602 -
International Journal of Molecular... May 2024Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor...
Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.
Topics: Animals; Paclitaxel; TRPM Cation Channels; TRPV Cation Channels; Ganglia, Spinal; Rats; Neuralgia; Male; Rats, Sprague-Dawley; Hyperalgesia; Capsaicin; Neurons
PubMed: 38892000
DOI: 10.3390/ijms25115813 -
BMC Plant Biology Jun 2024This study examines the impact of titanium dioxide nanoparticles (TiONPs) on gene expression associated with menthol biosynthesis and selected biochemical parameters in...
Studying the impact of titanium dioxide nanoparticles on the expression of pivotal genes related to menthol biosynthesis and certain biochemical parameters in peppermint plants (Mentha Piperita L.).
BACKGROUND
This study examines the impact of titanium dioxide nanoparticles (TiONPs) on gene expression associated with menthol biosynthesis and selected biochemical parameters in peppermint plants (Mentha piperita L.). Menthol, the active ingredient in peppermint, is synthesized through various pathways involving key genes like geranyl diphosphate synthase, menthone reductase, and menthofuran synthase. Seedlings were treated with different concentrations of TiONPs (50, 100, 200, and 300 ppm) via foliar spray. After three weeks of treatment, leaf samples were gathered and kept at -70 °C for analysis.
RESULTS
According to our findings, there was a significant elevation (P ≤ 0.05) in proline content at concentrations of 200 and 300 ppm in comparison with the control. Specifically, the highest proline level was registered at 200 ppm, reaching 259.64 ± 33.33 µg/g FW. Additionally, hydrogen peroxide and malondialdehyde content exhibited a decreasing trend following nanoparticle treatments. Catalase activity was notably affected by varying TiONP concentrations, with a significant decrease observed at 200 and 300 ppm compared to the control (P ≤ 0.05). Conversely, at 100 ppm, catalase activity significantly increased (11.035 ± 1.12 units/mg of protein/min). Guaiacol peroxidase activity decreased across all nanoparticle concentrations. Furthermore, RT-qPCR analysis indicated increased expression of the studied genes at 300 ppm concentration.
CONCLUSIONS
Hence, it can be inferred that at the transcript level, this nanoparticle exhibited efficacy in influencing the biosynthetic pathway of menthol.
Topics: Titanium; Mentha piperita; Menthol; Nanoparticles; Gene Expression Regulation, Plant; Plant Proteins; Plant Leaves; Metal Nanoparticles; Genes, Plant; Hydrogen Peroxide
PubMed: 38862885
DOI: 10.1186/s12870-024-05228-9 -
Proceedings of the National Academy of... Jun 2024Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP...
Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.1), which is defective in cardiac LQT1 syndrome, is, in addition to its known function in the heart, a highly relevant and sex-specific sensor of moderately cold temperatures. We found that KCNQ1 is expressed in skin and dorsal root ganglion neurons, is sensitive to menthol and cooling agents, and is highly sensitive to moderately cold temperatures, in a temperature range at which TRPM8 is not thermosensitive. C-fiber recordings from mice displayed altered action potential firing properties. Strikingly, only male mice showed substantial deficits in cold avoidance at moderately cold temperatures, with a strength of the phenotype similar to that observed in animals. While sex-dependent differences in thermal sensitivity have been well documented in humans and mice, is the first gene reported to play a role in sex-specific temperature sensation. Moreover, we propose that KCNQ1, together with TRPM8, is a key instrumentalist that orchestrates the range and intensity of cold sensation.
Topics: Animals; Male; Cold Temperature; Female; Mice; KCNQ1 Potassium Channel; Mice, Knockout; Ganglia, Spinal; Thermosensing; TRPM Cation Channels; Mice, Inbred C57BL; Action Potentials; Sex Characteristics; Menthol
PubMed: 38857404
DOI: 10.1073/pnas.2322475121 -
PloS One 2024The recommendation for Chlorhexidine (CHX) as a traditional oral care solution is decreasing, and herbal oral care products are being considered as a potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The recommendation for Chlorhexidine (CHX) as a traditional oral care solution is decreasing, and herbal oral care products are being considered as a potential alternative. This network meta-analysis aims to determine if herbal oral care products for oral care in mechanically ventilated patients are superior to CHX and provide direction for future research by comparing the effectiveness of herbal oral care products currently available.
MATERIALS AND METHODS
We searched for English-language published and grey literature sources of randomized clinical trials involving herbal oral care solutions in intensive care unit (ICU) oral care (until September 2023). The primary outcome was the incidence of ventilator-associated pneumonia (VAP); the secondary outcome was the oral microbiota quantity. Data were pooled by pairwise meta-analysis and Bayesian network meta-analysis. The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence was evaluated using the GRADE framework.
RESULTS
Our network meta-analysis included 29 studies, and the results showed that Chinese herb (OR: 0.39, 95% CI: 0.2-0.75) and Miswak (OR: 0.27, 95% CI: 0.07-0.91) were more effective in reducing VAP incidence than CHX. In terms of reducing bacterial counts, Chinese herb (OR: 0.3, 95% CI: 0.19-0.48) was superior to CHX, and all herbal oral care products, including Persica® (alcoholic extract of S. persica, Achillea millefolium, and Mentha spicata), Matrica® (Chamomile extract), and Listerine® (main components include Menthol, Thymol, and Eucalyptol), were better than saline in all aspects but without significant differences.
CONCLUSION
Based on our network meta-analysis, we have observed that Chinese herbal medicine and Miswak are superior to CHX in reducing the incidence of VAP. However, the safety and feasibility of traditional Chinese herbal medicine require further high-quality research for validation. Simultaneously, Matrica® demonstrates a significant reduction in microbial counts but does not exhibit a significant advantage in lowering the incidence of VAP. This observation aligns with the results of clinical double-blind trials. Therefore, we identify Miswak and Matrica® as promising herbal oral care products with the potential to replace CHX. It is essential to emphasize that our study provides guidance for future research rather than conclusive determinations.
REGISTRATION
PROSPERO no. CRD42023398022.
Topics: Pneumonia, Ventilator-Associated; Humans; Randomized Controlled Trials as Topic; Network Meta-Analysis; Chlorhexidine; Mouthwashes; Bayes Theorem; Intensive Care Units
PubMed: 38848351
DOI: 10.1371/journal.pone.0304583 -
Heliyon Jun 2024To extend the vase life of cut flowers, there is now a trend of using plant essential oils in place of synthetic chemicals, as they are fully biodegradable, more...
To extend the vase life of cut flowers, there is now a trend of using plant essential oils in place of synthetic chemicals, as they are fully biodegradable, more eco-friendly, and safer. The objective of this study was to examine the possible application and postharvest quality effects of three plant essential oils namely, ginger ( Roscoe), peppermint ( L.), and citronella ( Rendle), as natural vase solution for cut flowers. Peppermint essential oil showed promise as a holding solution for extending the vase life of orchids. To confirm vase life extension, emulsions containing peppermint essential oil at concentrations of 50 and 100 μg mL combined with 4 % glucose to formulate holding solutions applied to orchids. Vase life, some biochemical changes, electrolyte leakage, total microbial count in the holding solution, and physical condition via scanning electron microscopy (SEM) were evaluated over a period of 25 days. The three major compounds in peppermint essential oil were identified as menthol (33.24 %), 1-menthone (18.91 %) and menthofuran (14.85 %). The essential oil was applied in emulsion form as a holding solution. Treatment with 4 % glucose and either 50 or 100 μg mL peppermint essential oil prolonged the vase life of orchids to up to 28 days. Scanning electron microscopy on Day 7 showed that the xylem vessels of treated orchids remained clear, suggesting reduced microbial plugging at the stalk end. Similarly, on Day 20, a reduced microbial cell count was observed for treated orchids (<1 log CFU mL) in comparison with controls (7.20 ± 0.04 log CFU mL). Finally, the essential oil improved flower quality by helping preserve petal membrane stability and petal anthocyanin content. Our results suggest the application of peppermint essential oil as a novel alternative to chemicals used in holding solutions for extending the vase life of orchids.
PubMed: 38845939
DOI: 10.1016/j.heliyon.2024.e31636 -
PloS One 2024A Pickering emulsion was synergistically stabilised with zein nanoparticles (ZNPs) and starch nanocrystals (SNCs) to prepare it for menthol loading. After response...
Synergistic stabilization of a menthol Pickering emulsion by zein nanoparticles and starch nanocrystals: Preparation, structural characterization, and functional properties.
A Pickering emulsion was synergistically stabilised with zein nanoparticles (ZNPs) and starch nanocrystals (SNCs) to prepare it for menthol loading. After response surface optimisation of the emulsion preparation conditions, a Pickering emulsion prepared with a ZNPs:SNCs ratio of 1:1, a particle concentration of 2 wt% and a water:oil ratio of 1:1 provided the highest menthol encapsulation rate of the emulsions tested (83%) with good storage stability within 30 days. We examined the bilayer interface structure of the emulsion by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The results of simulated digestion experiments showed that the release rate of free fatty acid was 75.06 ± 1.23%, which ensured bioavailability. At the same time, the emulsions facilitated the slow release of menthol. Bacteriostatic studies revealed that the Pickering emulsion had a protective effect on menthol, with the most significant inhibitory effects on Escherichia coli and Staphylococcus aureus under the same conditions. Overall, this study proposes a novel approach for the application and development of l-menthol by combining it with Pickering emulsion.
Topics: Menthol; Emulsions; Nanoparticles; Zein; Starch; Staphylococcus aureus; Escherichia coli; Anti-Bacterial Agents; Particle Size
PubMed: 38843222
DOI: 10.1371/journal.pone.0303964 -
Ecotoxicology and Environmental Safety Jul 2024Effective removal of organic UV filters from aquatic environmental compartments and swimming waters is very important because these substances are hazardous to humans...
Effective removal of organic UV filters from aquatic environmental compartments and swimming waters is very important because these substances are hazardous to humans and wildlife at low concentrations and act as endocrine disruptors. Therefore, the aim of the present article is to determine the extraction efficiencies of hydrophobic deep eutectic solvents (HDES) for the selected UV filters based on benzophenone structure (benzophenone, 2,4-dihydroxybenzophenone, 2,2´,4,4´-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2´-dihydroxy-4-methoxybenzophenone, 4-methacryloxy-2-hydroxybenzophenone) from aqueous matrices. For this purpose, six HDESs based on dl-menthol in combination with caprylic, decanoic and lauric acid are prepared and compared with referent terpene solvents such as terpineol and linalool. The effect of various parameters such as HDES composition, volume ratio, frequency and shaking time are studied. The highest extraction efficiency is shown by HDES of menthol:caprylic acid (1:1) composition at the aqueous:organic phase volume ratio of 1:1, shaking frequency of 1500 rpm and shaking time of 15 min. The achieved extraction efficiencies are higher than 99.6 % for all benzophenones studied in the purification of stagnant pond water, swimming pool water and river water samples. After a simple and fast sample treatment, the residual levels of benzophenones in the waters are controlled by a newly developed sensitive HPLC-MS/MS method with LOQs in the range of 0.7 - 5.0 ng/mL.
Topics: Benzophenones; Water Pollutants, Chemical; Sunscreening Agents; Hydrophobic and Hydrophilic Interactions; Water Purification; Deep Eutectic Solvents; Menthol; Caprylates
PubMed: 38820821
DOI: 10.1016/j.ecoenv.2024.116528