THE RELATIONSHIP BETWEEN THERMAL PAIN SENSATION, FREE TESTOSTERONE, TRPV1, MOR LEVELS AND VARIOUS DEGREES OF HOSTILITY IN YOUNG HEALTHY MALES.

Large number of studies consider gonadal hormones as factors influencing pain perception by changing the activity of nociceptive and antinociceptive systems. Recent studies indicate that testosterone, along with some other gonadal hormones, plays a key role in the regulation of TRPV1 and MOR expression. In addition, some works focus on the relationship between pain sensation and hostility indices, as well as their interaction with gonadal hormones. The purpose of this study is to elucidate the relationship of thermal sensation and pain threshold with free testosterone, transient receptor potential cation channel subfamily V member 1(TRPV1) and µ-opioid receptor (MOR) protein levels as well as various degrees of hostility in young healthy males. Significant positive correlation is found between heat pain threshold, free testosterone and MOR levels. Each of these parameters significantly correlates positively with various degrees of assault and insignificantly with that of verbal and indirect hostility. They also significantly correlate negatively with various degrees of irritability, resentment, suspicion and guilt. Significant negative correlation is detected between heat pain threshold and TRPV1 level as well as free testosterone and TRPV1 level. The relationship among cold pain threshold, free testosterone, TRPV1, MOR levels and hostility indices is insignificant. Consequently, we consider it to the purpose to further studies in this direction including interaction among other forms of pain sensation and psychological indices.

[CORRELATION BETWEEN HEAT PAIN THRESHOLD DEGREE AND TRPV1 RECEPTOR PROTEIN LEVEL OVER VARIOUS PHASES OF THE OVARIAN-MENSTRUAL CYCLE].

Numerous scientific studies demonstrating differences in pain sensitivity over various phases of the ovarian-menstrual cycle (OMC) in healthy women have been published in recent decades, but the basis for these differences is however still poorly understood. The aim of the current study was to assess the correlation between the heat pain threshold degree and the dynamics of TRPV1 (Transient receptor potential channeling subfamily V member1) receptor protein level, as well as aggression degree in healthy women in the follicular and luteal phases of OMC. An increased TRPV1 receptor protein level and a decreased thermal pain threshold were found in the luteal phase of the OMC. The study revealed a correlation of the progesterone level in the luteal phase with a degree of increase of TRPV1 level, as well as with the degree of decrease of heat pain threshold. The relationship between the degree of pain threshold, as well as TRPV1 level with follicle stimulating (FSH), luteinizing (LH) hormones and prolactin levels was not found. Also, there was no correlation between TRPV1 or heat pain threshold levels and aggression degree.

Transient receptor potential vanilloid 2 (TRPV2), a potential novel biomarker in childhood asthma.

BACKGROUND: The presence of transient receptor potential vanilloid 2 (TRPV2) in human peripheral blood cells may suggest a role under pathological conditions. The aim of this study was to explore the relationship between the expression profile of TRPV2 gene and childhood asthma in the north of China. The effects of allergens exposure on the expression of TRPV2 gene were also investigated. METHODS: Sixty asthmatics children confirmed by physician diagnosis and 60 healthy children as a control group were recruited. Serum total IgE and specific IgE were measured. Using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), TRPV2 was detected in total RNA extracted from peripheral blood lymphocytes. Student's t-test and chi-square test were used to analyze the relationship between TRPV2 transcript and different parameter variables on susceptibility of childhood asthma. Multiple logistic regression was used to analyze the associations between TRPV2 gene and allergens. RESULTS: The expression level of TRPV2 gene was increased 2.6 times in asthmatic children compared with controls (p < .01). The up-regulation of TRPV2 gene and sensitization to one of three the allergens-spring pollen, dust mite, and dog and cat hair-were correlated with childhood asthma. In addition, the hypersensitivity to spring pollen, cockroach, and dust mite and up-regulation of TRPV2 gene expression may be the risk factors for the childhood asthma in Beijing. CONCLUSIONS: The increased expression of TRPV2 gene in peripheral lymphocytes is closely correlated with childhood asthma in the north of China. This study provides a potential new biomarker of childhood asthma and lays the basis for further clarification of the pathogenesis underlying asthma.

[The functional characteristics oF TRPV5 and TRPV6 channels in normal and transformed human blood lymphocytes].

Calcium signaling and Ca(2+)-conducting channels are involved in the development of immune response, cell proliferation, growth and differentiation of lymphocytes. In this paper the calcium channels TRPV5 and TRPV6 (transient receptor potential vanilloid channels) were studied in the plasma membrane of T cell line Jurkat and normal human blood lymphocytes. The channels were activated by removing Ca2+ and Mg2+ from surrounding solution, characterized by inward rectification, and were inactivated by the effective blocker of TRPV5 and TRPV6, ruthenium red. Channel activity was significantly higher in Jurkat cells, than in normal human lymphocytes. Quantitative PCR analysis revealed higher levels of mRNA genes encoding channels TRPV5 and TRPV6 in the proliferation cells compared with resting lymphocytes. In general these data showed that TRPV5/TRPV6 in human lymphocytes are functionally active, and their activity is associated with proliferative status of blood cells.

Redox modulation of Ecto-NOX1 in human platelets.

By modulating the cellular redox state, the plasma membrane electron transport (PMET) is important in platelet biology; indeed, the oxidant/antioxidant balance plays a central role during activation of the coagulation pathway. None the less, in human platelets, the PMET system has not yet been fully characterized and the molecular identities of most components are unknown. Here, for the first time, the presence of the plasma membrane hydroquinone (NADH) oxidase Ecto-NOX1 in human platelets has been described. We found that Ecto-NOX1 expression is modulated by capsaicin: Indeed, it is positively regulated through a mechanism requiring binding of capsaicin to its receptor, namely the transient receptor potential vanilloid subtype 1 (TRPV1). Ligand-receptor interaction triggers a signalling cascade leading to ROS production, which in turn enhances expression and activity of Ecto-NOX1. Redox regulation of Ecto-NOX1 may be important to platelet recruitment and activation during inflammatory diseases.

TRPV6 Is Associated with Prognosis of ST-Elevation Acute Myocardial Infarction.

OBJECTIVE: To investigate the relationship between Transient Receptor Potential Vanilloid 6 (TRPV6) and ST-elevation acute myocardial infarction (STEMI) patients. METHODS: This observational research included a total of 221 patients with STEMI admitted during January 2017~August 2019. Additionally, 50 cases of non-ST-elevation acute myocardial infarction (NSTEMI) patients and 50 healthy individuals were enrolled as the control. Serum levels of TRPV6 were detected by ELISA method. The relationship between TRPV6, clinical characteristics, laboratory indices of CK-MB, TnI, NT-pro-B-type natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), and the left ventricular ejection fraction (LVEF%) was analyzed by statistical methods. K-M curve was performed for survival time. RESULTS: Serum levels of TRPV6 were remarkably lower in STEMI and NSTEMI patients compared with the healthy control. Levels of NT-pro-BNP and CK-MB were significantly higher and serum levels of TRPV6 were dramatically lower in deceased STEMI patients in comparison with the surviving patients. The levels of TRPV6 were negatively correlated with CK-MB and NT-pro-BNP. Meanwhile, TRPV6 was negatively expressed in tissues of STEMI patients and positively expressed in normal tissues. Patients with lower TRPV6 levels had remarkably lower LVEF ratio, higher GRACE scores, higher CK-MB and NT-pro-BNP levels, as well as higher ratios of cardiovascular death, malignant arrhythmia, cumulative MACE, and shorter survival time than patients with higher TRPV6. CONCLUSION: The lower expression of TRPV6 was associated with poor clinical outcomes and prognosis of STEMI patients.

Upper airway cough syndrome in children and two inflammatory factors: TRPV1 and TGF-ß2.

OBJECTIVES: The aim of the study was to investigate upper airway cough syndrome (UACS) in children and to determine alternative methods to explore the relationships among TRPV1, TGF-ß2, and UACS. METHODS: In 2012, 104 children with adenoid hypertrophy aged 2-13 years who were admitted to the otolaryngology department, Capital Institute of Pediatrics-affiliated children's hospital, were included in this study. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) studies for TRPV1 and TGF-ß2 were performed to understand the relationship between the two inflammatory factors, and the correlations among the indices and UACS. The research was divided into three stages. In stage 1, 72 children (24 UACS and 48 controls) were enrolled in the study, and ELISAs for TRPV1 and TGF-ß2 were performed. In stage 2, 32 children (16 UACS and 16 controls) were enrolled in the study and both ELISA and IHC for TRPV1 and TGF-ß2 were performed. In stage 3, 41 children were enrolled in this research who had thick mucus secretions in the posterior nasal apertures in stage 1 and 2 (23 cases with chief complaint (or history) of chronic cough and 18 cases without). The difference between the TRPV1 and TGF-ß2 serum values and the clinical factors was determined. RESULTS: The levels of TRPV1 and TGF-ß2 were significantly increased in the UACS cases. OSAHS and thick mucus secretions correlated with a diagnosis of UACS. A history of asthma and thick mucus secretions correlated with elevation of the two inflammatory factors. There was no statistical correlation between ELISA and IHC testing. Among the children with thick mucus secretions, some had a higher possibility of chronic coughing including those who had higher levels of the two indices, larger tonsils and a history of chronic tonsillitis. CONCLUSION: The detections of TRPV1 and TGF-ß2 from serum and adenoid body specimens are valuable for UACS auxiliary diagnosis. Tonsil hypertrophy and chronic tonsillitis history are independent risk factors of UACS.

Oral and topical pharmacokinetic studies of a novel TRPV1 antagonist, PAC-14028 in rats and minipigs using liquid chromatography/tandem mass spectrometric method.

PAC-14028 ((E)-N-((R)-1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl)-3-(2-propyl-6-trifluoromethyl-pyridine-3-yl)-acrylamide) is a novel and potent transient receptor potential vanilloid type I (TRPV1) antagonist. We developed and validated a rapid, sensitive and selective liquid chromatography/tandem mass spectrometric method for determination of PAC-14028 in rat and minipig plasma. After protein precipitation PAC-14028 and internal standard (methylated analog, PAC-14026) were separated on a Symmetry C(18) column (4.6 mm × 75 mm, 3.5 µm) with an isocratic mobile phase, acetonitrile: water (8:2, v/v) containing 0.2% formic acid and monitored by electrospray positive ionization with multiple reaction monitoring mode (PAC-14028, 492→156; IS, 506→156, m/z). The calibration curve was linear over the range of 1.0-500 ng/ml (r(2)>0.999) and lower limit of quantitation (LLOQ) was 1 ng/ml. The precision and accuracy were within ± 15% and the stability was acceptable during bench-top, auto-sampler, 3 freeze-thaw cycles and 4-week storage in a freezer at -80°C. This method was successfully applied to the intravenous, oral and topical pharmacokinetic studies of PAC-14028 in rats and minipigs, which showed comparable pharmacokinetic parameters (T1/2, 2.1h and 3.8h; F%, 52.7% and 64.2% for rats and minipigs, respectively). Percutaneous absorption of PAC-14028 was negligible after topical application (F% 0.2-1.7%).

L-arginine import via cationic amino acid transporter CAT1 is essential for both differentiation and proliferation of erythrocytes.

In the present study, we examined the role in hematopoiesis of cationic amino acid transporter 1 (CAT1), which transports L-arginine, L-lysine, L-ornithine, and L-histidine. The expression level of human CAT1 (hCAT1) mRNA in mononuclear cells (MNCs) fractionated according to lineage-selective markers was examined by reverse transcriptase-polymerase chain reaction. The expression of CAT1 in glycophorin A-positive erythroid cells was 8 times higher than in nonfractionated MNC (control) cells. Characteristics of L-arginine uptake by K562 cells, an established leukemic cell line used as an erythroid model, were similar to those of CAT1 in regards to saturation kinetics, sodium independence, and substantial inhibition of L-arginine uptake by N-ethylmaleimide, which is a specific inhibitor of system y+ amino acid transporter. Removal of L-arginine from the culture medium prevented both proliferation and differentiation of K562 cells, while removal of L-lysine or L-histidine had little effect on differentiation, though proliferation was blocked. Hematopoietic stem cells obtained from human cord blood failed to develop into erythroid cells in the absence of L-arginine in the culture medium. These findings indicate that hCAT1 is involved in erythroid hematopoiesis through its role in importing L-arginine, which appears to be essential for the differentiation of red blood cells.