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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 -
Advanced Science (Weinheim,... Jun 2024It remains a great challenge to achieve strong and reversible hydrogel adhesion. Hydrogel adhesives also suffer from poor environmental stability due to dehydration. To...
It remains a great challenge to achieve strong and reversible hydrogel adhesion. Hydrogel adhesives also suffer from poor environmental stability due to dehydration. To overcome these problems, here reversible adhesive gels are designed using a new switching mechanism and new solvent. For the first time, the study observes UCST (upper critical solution temperature)-type thermosensitive behaviors of poly(benzyl acrylate) (PBnA) polymer and gel in menthol:thymol deep eutectic solvents (DESs). The temperature-induced phase transition allows adjusting cohesive force, and hence adhesion strength of PBnA gels by temperature. To further improve the mechanical and adhesion properties, a peptide crosslinker is used to allow energy dissipation when deforming. The resulting eutectogel exhibits thermal reversible adhesion with a high switching ratio of 14.0. The adhesion strength at attachment state reaches 0.627 MPa, which is much higher than most reversible adhesive hydrogels reported before. The low vapor pressure of DES endows the gel excellent environmental stability. More importantly, the gel can be repeatedly switched between attachment and detachment states. The strong and reversible gel adhesive is successfully used to design soft gripper for the transport of heavy cargos and climbing robot capable of moving on vertical and inverted surface in a manner similar to gecko.
PubMed: 38885493
DOI: 10.1002/advs.202400938 -
Chemphyschem : a European Journal of... Jun 2024An electrochemical N-acylation of sulfoximine has been achieved via the coupling of α-keto acids and NH-sulfoximines. This process involves the sequential cleavage of...
An electrochemical N-acylation of sulfoximine has been achieved via the coupling of α-keto acids and NH-sulfoximines. This process involves the sequential cleavage of C-C bond followed by C(sp2)-N bond formation, with the liberation of H2 and CO2 as the by-products. A library of N-aroylated sulfoximines is produced via the coupling of aroyl and sulfoximidoyl radicals by anodic oxidation under constant current electrolysis (CCE). The compatibility of the present protocol has been demonstrated by coupling of various bio-active compounds, such as NH-sulfoximine derived from (-)-borneol, L-menthol, D-glucose derivative, and some commercial drugs such as flurbiprofen, and ibuprofen. This late-stage functionalization highlights the importance of this sustainable protocol. Besides this, various control experiments and detection of H2 evolution have been performed to support the proposed mechanism.
PubMed: 38884606
DOI: 10.1002/cphc.202400599 -
Bioprocess and Biosystems Engineering Jun 2024The present study optimized pre-treatment conditions for bioenzyme-mediated hydro-distillation (BMHD) for extraction of mint oil from mentha leaves and the results were...
The present study optimized pre-treatment conditions for bioenzyme-mediated hydro-distillation (BMHD) for extraction of mint oil from mentha leaves and the results were compared with those of traditional hydro-distillation (HD) method using response surface methodology. The bio-enzymes produced from moringa leaves had maximum pectinase activity (287.04 µg of sugar/min/ml) followed by xylanase (87.78 µg of sugar/min/ml) while endoglucanase, exoglucanase and amylase activities were comparatively low. The optimized conditions for HD were 69.08 temperature for 173.70 min with water:sample of 10.0. The optimized conditions for enzyme pre-treatment of mentha leaves by BMHD were enzyme concentration of 8%, for a period of 120 min at an incubation period of 40 ℃. The yield (%) and menthol content (%) of the oil at optimized conditions by HD were 1.55 ml/100 g of sample and 56.40% menthol content, respectively, and for BMHD the yield and menthol content (%) of the oil at optimized conditions were 3.69% and 72.80%, respectively. It was found that BMHD leads to a 130% increase in the yield of mint oil and a 10% increase in menthol content as compared to the HD method. No significant difference in physical parameters was observed in mint oil extracted via both methods. Therefore, BMHD is a cost-effective and sustainable approach having an edge over the HD method without compromising the quality and could be a viable approach for commercial purposes.
PubMed: 38874619
DOI: 10.1007/s00449-024-03041-0 -
Drug and Alcohol Dependence May 2024In addition to imparting flavor, menthol in menthol-flavored cigarettes enhances nicotine addiction and increases experimentation, initiation, and progression to regular... (Review)
Review
INTRODUCTION
In addition to imparting flavor, menthol in menthol-flavored cigarettes enhances nicotine addiction and increases experimentation, initiation, and progression to regular smoking. Menthol can be added to cigarettes at perceptible levels (so-called flavored cigarettes or characterized flavored cigarettes) or non-perceptible levels (subliminal). Our objective was to understand the reasons that tobacco companies use subliminal menthol.
METHODS
We identified previously secret internal tobacco company documents dated 1955-2012 in the Truth Tobacco Industry Documents archive on menthol at subliminal levels.
RESULTS
Beginning in at least the 1950s, tobacco companies used subliminal menthol to compensate the flavor loss caused by filters, reduce smoke harshness, reduce dryness, and increase smoke coolness. Varying menthol concentrations were considered to help convert people who smoke non-menthol to menthol brands, possibly because people who use menthol cigarettes have more harship quitting than people who use non-menthol cigarettes.
CONCLUSIONS
Menthol is an important additive beyond its function as a "characterizing flavor." Tobacco companies use menthol in "non-menthol" cigarettes at subliminal (non-perceptible by the people who smoke cigarettes) levels to improve taste, make them easier to smoke and facilitate initiation, and possibly convert people who smoke non-menthol cigarettes to menthol cigarettes.
PubMed: 38870568
DOI: 10.1016/j.drugalcdep.2024.111346 -
Journal of Public Health Management and...In June 2020, Massachusetts became the first state to implement a comprehensive flavored tobacco restriction. One concern was that Massachusetts residents would travel...
In June 2020, Massachusetts became the first state to implement a comprehensive flavored tobacco restriction. One concern was that Massachusetts residents would travel to New Hampshire to purchase restricted products. This article assesses tobacco sales in both states post-law implementation. Retail scanner data were obtained from the Nielsen Company and Information Resources, Inc (IRI), from 1 year pre-law implementation to 2 years post-law implementation. Data post-law implementation were compared with data from 1 year pre-law implementation (baseline). In Massachusetts, 2 years post-law implementation, flavored and menthol tobacco sales decreased by more than 90%. Total sales decreased by around 20%. In New Hampshire, menthol tobacco sales increased (25.1% in IRI and 18.2% in Nielsen), but total sales changed minimally (<5% increase in IRI, <5% decrease in Nielsen). When data from both states were combined, total sales decreased by around 10%. The net decrease in total tobacco sales across Massachusetts and New Hampshire indicates Massachusetts' flavored tobacco restriction resulted in a reduction in tobacco sales despite potential cross-border purchases.
Topics: Massachusetts; New Hampshire; Humans; Commerce; Tobacco Products; Flavoring Agents
PubMed: 38870369
DOI: 10.1097/PHH.0000000000001869 -
Nicotine & Tobacco Research : Official... Jun 2024Herbal cigarettes are made with non-tobacco plant materials (e.g., tea leaves, hemp), are typically sold pre-rolled in packs and with filters, and are combusted and...
INTRODUCTION
Herbal cigarettes are made with non-tobacco plant materials (e.g., tea leaves, hemp), are typically sold pre-rolled in packs and with filters, and are combusted and smoked like tobacco cigarettes. Herbal cigarette manufacturers have a history of making misleading health claims and at least one company has previously settled with the US Federal Trade Commission over deceptive advertising. This study examined current claims and product characteristics of herbal cigarettes sold by a popular online retailer.
METHODS
We searched Amazon.com for "herbal cigarettes" and "hemp cigarettes" and identified all herbal cigarette products sold on the first page of search results (n=51). Two coders independently content analyzed each product's Amazon page for claims (e.g., smoking cessation, health), product characteristics (e.g., flavors), and presence of disclaimers and warnings.
RESULTS
Overall, 78.4% of product pages made smoking cessation claims (e.g., "A more scientific way to quit smoking", "…decreases nicotine craving symptom and helps to quit tobacco smoking"). Further, 45.1% of product pages included claims describing lower risk/exposure compared to tobacco products (e.g., "…without the addictive nicotine and toxic chemicals found in tobacco cigarettes"). Some herbal products were available in multiple flavors, including menthol (21.6%) and fruit (17.7%). Only 35.3% of products included visible health warnings on product packaging.
CONCLUSIONS
Many herbal cigarette products sold on Amazon.com make unauthorized cessation and health claims. Regulatory agencies must act decisively to stop the misleading advertising of these products and develop appropriate warnings to educate the public about the potential harms of herbal cigarettes.
IMPLICATIONS
This content analysis documents the use of unauthorized and misleading claims made in the marketing of herbal cigarettes.These findings highlight the need for enforcement of existing federal regulations, which prohibit deceptive advertising.Research is needed to inform the development of appropriate warning labels that can be used to inform consumers of the potential harms of smoking herbal cigarettes.
PubMed: 38869253
DOI: 10.1093/ntr/ntae142 -
Preventive Medicine Jun 2024Flavors enhance nicotine e-cigarette appeal by altering sensory experience. Females may be more sensitive to tobacco-associated cues and uniquely affected by flavor. The...
OBJECTIVE
Flavors enhance nicotine e-cigarette appeal by altering sensory experience. Females may be more sensitive to tobacco-associated cues and uniquely affected by flavor. The current study is an exploratory analysis to examine differences by sex on reward, appeal, and sensory experience of popular e-cigarette flavors.
METHODS
Adults (N = 121) who use cigarettes (≥1 cigarette/day) were enrolled in a laboratory study in which they vaped four e-cigarette flavors (tobacco, cherry, menthol, vanilla; in separate lab sessions) in one of two freebase nicotine concentrations (6 mg/ml,18 mg/ml). Following exposures, participants rated e-cigarette reward using the Drug Effects Questionnaire (DEQ), flavor and overall e-cigarette appeal using Labeled Hedonic Scales (LHS), and intensity of flavor, irritation, coolness, fruitiness, and sweetness using Generalized Labeled Magnitude Scales (gLMS). Linear mixed models were conducted for outcomes to analyze effects of sex, flavor, and sex x flavor interaction.
RESULTS
For DEQ ratings, there was a trend (p = .08) toward a sex x flavor interaction, in which menthol flavor produced more reward than other flavors for females, but not males. For LHS ratings, there was a significant sex x flavor interaction (p = .03) for overall e-cigarette experience with females but not males rating menthol higher than other flavors. All gLMS scales but irritation showed that females generally had greater differences between flavors compared to males (ps ≤ 0.03).
CONCLUSION
Menthol in e-cigarettes may play an important role in mediating appeal and/or reward among females. This may be due in part to their ability to better detect sensory effects of e-cigarettes.
PubMed: 38866212
DOI: 10.1016/j.ypmed.2024.108040 -
Organic & Biomolecular Chemistry Jun 2024A previously elusive organocatalytic protocol for the esterification of amides is disclosed. DABCO (10 mol%) is identified as an effective catalyst for the...
A previously elusive organocatalytic protocol for the esterification of amides is disclosed. DABCO (10 mol%) is identified as an effective catalyst for the esterification of -pivaloyl amides. Although -pivaloyl amides are nearly planar (amide bond twist () = 4.54° and pyramidalization ( = 6.39°)) and resonance stabilized, esterification is achieved with high efficiency. The developed protocol is generic, phenols, thiophenols, aliphatic alcohols, and thiols were identified as effective substrates. Furthermore, the reaction features a broad substrate scope and excellent functional group tolerance. To exemplify the practical applicability of the developed protocol, the esterification of bioactive natural products, pterostilbene and menthol, is demonstrated. In addition, a series of competitive experiments were conducted to establish the reactivity pattern of alcohols, thiols, and phenols, which could serve as selectivity principles for future synthetic design. Our findings signify a notable advancement in utilizing amides as versatile synthetic building blocks in organic synthesis under metal-free conditions.
PubMed: 38864233
DOI: 10.1039/d4ob00752b