Recent evidence supports the role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in a TRPM8 dependent and independent manner. The present study was designed to analyse whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to directlyinduce desired energy expenditure effects. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration during adipogenesis but did not alter the lipid accumulation as well as acute experiments were performed with lower dose of menthol on mature adipocytes In conclusion, the present study provides evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue However, critical dose characterization for its clinical utility is required.
Antagonism of transient receptor potential vanniloid-1 (TRPV1) and desensitization of transient receptor potential ankyrin-1 (TRPA1) nociceptors alleviate inflammatory bowel diseases (IBD)-associated chronic pain. However, there is limited literature available about their role in regulating the mucosal layer, its interaction with host physiology, and luminal microbial community. The present study focuses on the effects’ intra rectal administration of capsazepine (modulator of TRPA1/TRPV1 expressing peptidergic sensory neurons) on colonic mucus production and gut health. We performed histological analysis, gut permeability alteration, gene expression changes, metabolite profiling, and gut microbial abundance in the ileum, colon, and cecum content of these animals. Intra rectal administration of capsazepine modulates TRPA1/TRPV1-positive nociceptors (behavioral pain assays) and resulted in damaged mucosal lining, increased gut permeability, and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response, and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. These results suggest that caution must be exercised before employing TRPA1/TRPV1 modulation as a therapeutic option to alleviate pain caused due to IBD.
In the present work, optical glass BK-7 was drilled by rotary ultrasonic machine. Response surface methodology was amalgamated with desirability approach to frame the experimental matrix and seek pragmatic solutions to cope with the real machining problems. Spindle speed, ultrasonic power and feed rate were extensively scrutinized to evaluate the machining proficiency in terms of material removal rate (MRR) and surface roughness (SR). Thereafter, ANOVA check was exercised to scrutinize the adequacy of developed SR and MRR models and cast light on the significant model terms with their impact intensity on responses. The feed rate was observed to be the most influential factor in determining the qualitative (SR) and quantitative (MRR) aspect of the machining process. The machined surface along with tool surface was examined by scanning electron microscope to shed light on the material fractography and tool wear. Processed surface topography revealed the concluding evidence of brittle fracture dominance along with few traces of plastic flow of material. Severe tool wear was observed in the initial stage of experimentation due to bond fracture and grain fracture. Confirmatory tests validated the prediction accuracy of developed models by keeping the error within 5% between the predicted and experimental value at 95% confidence level.
The use of dental hand pieces endanger dentists to vibration exposure as they are subjected to very high amplitude and vibration frequency. This paper has envisaged a comparative analysis of vibration amplitudes and transmissibility during idling and drilling with micro motor (MM) and air-turbine (AT) hand pieces. The study aims to identify the mean difference in vibration amplitudes during idling, explore different grasp forces while drilling with irrigant injection by the dentist, and various vibration transmission of these hand pieces. The study utilized 22 separate frequency resonances on two new and eight used MMs and two new and eight used ATs of different brands by observing the investigator at 16 different dentist clinics. The study adopted a descriptive research design with non–probability sampling techniques for selecting dentists and hand pieces. Statistical methods like Levene Test of Homogeneity, Welch ANOVA, independent t-test, and Games–Howell test were utilized with SPSS version 22 and MS-Excel. The results reveal that vibration amplitudes and vibration transmissibility when measured at position 2 are higher than in another position 1. Vibrations during idling for used MMs are more than AT hand pieces, and the used MM (MUD) and used AT (AUA) hand pieces differ due to their obsolescence and over-usage. Vibration amplitudes increase every time with the tightening of grasping of the hand piece. Vibration amplitudes for each grasping style of MM hand piece differ from all other grasping styles of AT hand pieces. Routine exposure to consistent vibrations has ill physical, mental, and psychological effects on dentists. The used hand pieces more hazardous as compared to newer ones. The study suggests that these hand pieces must be replaced periodically, sufficient to break between two operations, especially after every hand piece usage. Hence, the present research work can be further extended by creating some control groups among dentists and then studying the vibration amplitude exposure of various dental hand pieces and subsequent transmissibility to their body parts.
Short‐chain fatty acids (SCFAs), metabolites of colonic bacterial fermentation of complex carbohydrates, are closely related to the release of gut hormones. In this study, we examined the involvement of transient receptor potential ankyrin 1 (TRPA1) in SCFA‐induced increase in intracellular calcium ([Ca2+]i) and its impact on gut hormone secretion using naturally TRPA1 expressing intestinal secretin tumour cell‐1 (STC‐1) cell line. Individual SCFAs and their physiological mix enhanced calcium influx in TRPA1‐dependent manner. SCFA mix also significantly increased membrane expression of TRPA1. Gene expression studies revealed that SCFA mix elevated the expression of genes involved in calcium‐activated calcineurin pathway in TRPA1‐dependent manner and cAMP‐regulated transcriptional co‐activators (CRTC) pathway independent to TRPA1. Genes representing synaptic vesicular exocytosis and gut hormone precursors were significantly elevated with SCFA mix treatment. Treatment with TRPA1 antagonist HC‐030031 markedly reduced these effects. The release of gut hormones was elevated with 10 mm SCFA mix in TRPA1 dependent manner. Our in vivo prebiotic study results suggested presence of an environment conducive to increase in gut hormone secretion. Overall, our findings provide an evidence for the possible role of TRPA1 in SCFA‐induced increase in gut hormone secretion, hence another mechanism of action for prebiotics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.