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Objective To explore the expression of TRPV2 and its clinicopathological significance in oral squamous cell carcinoma (OSCC). Methods Immunohistochemistry and western blot were used to detect TRPV2 expression level in OSCC; Pearson χ² test to analyze the association between TRPV2 expression level and clinicopathological features of OSCC patients; log-rank test to analyze the effect of TRPV2 on survival. Bioinformatics method was used to explore the potential biological function of TRPV2, and immunohistochemistry to verify the relationship between TRPV2 and macrophage infiltration level. Results Immunohistochemistry and western blot confirmed that TRPV2 was highly expressed in OSCC (P < 0.05). TRPV2 expression was significantly correlated with T stage, tumor histological grade and poor prognosis (P < 0.05). Bioinformatics method found that TRPV2 participated in PI3K/AKT pathway and regulated the level of immune cell infiltration; TRPV2 expression had strong positive correlation with the macrophage infiltration level (R = 0.562, P < 0.001). Conclusion The expression of TRPV2 is highly expressed in OSCC and associated with poor prognosis, and may take part in the occurrence and development of OSCC by regulating immune response and PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biological coral artificial bone is a good alternative material for repairing long bone defects. However, the degradation and absorption rate of biological coral artificial bone in the human body does not match the growth rate of new bone, which leads to the limitation of its clinical application. OBJECTIVE: To explore the effect of osteoclast TRPV5 on the degradation of biological coral artificial bone. METHODS: Monocyte macrophage strain RAW264.7 from mouse was inoculated on biological coral artificial bone slices, which were co-cultured with osteoclasts. After the appearance of osteoclasts was observed, the osteoclast-induced differentiation medium containing 0, 50, 500, 5 000 µmol/L ruthenium red (TRPV5 channel inhibitor) was added separately. After culturing for a certain period of time, the expression of TRPV5 channel protein was observed under a laser confocal microscope. The absorption lacuna on the biological coral artificial bone slice was observed under a scanning electron microscope. The expression of TRPV5 channel protein in cells was detected by western blot assay. RESULTS AND CONCLUSION: (1) Laser scanning confocal microscope: TRPV5 could be expressed on the cytoplasm and membrane of osteoclasts. With the increase of ruthenium red concentration, the expression of TRPV5 on osteoclasts decreased. (2) Scanning electron microscope: Large continuous bone resorption lacuna was seen on the bone slices in the 0 nmol/L ruthenium red group. The bone resorption lacuna on the bone slices in other concentrations of ruthenium red decreased and was scattered, and with the increase of the concentration of ruthenium red, the area of the bone lacuna gradually decreased. (3) Western blot assay: Compared with 0 nmol/L ruthenium red group, the expression of TRPV5 channel protein in other concentrations of ruthenium red groups was significantly decreased (P < 0.05 or P < 0.01). (4) The results confirm that osteoclasts grow well on biological coral artificial bone, and TRPV5 can be used as a target to regulate the degradation rate of biological coral artificial bone. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: The transient receptor potential vanilloid 4 (TRPV4) agonist GSK1016790A can activate TRPV4 protein and induce Ca2+ influx in a short time, while its expression remains unchanged. However, during culture, the decreased expression of TRPV4 on HeLa cell membrane surface was induced by GSK1016790A. Whether the phenomenon had an effect on neural regeneration is still not clear. OBJECTIVE: To explore the effect of TRPV4 agonist GSK1016790A on axonal regeneration in different periods. METHODS: The dorsal root ganglion cells of ICR mouse at 6-8 weeks were treated by collagenase and trypsin for cell culture. In the 2-hour group, the agonist GSK1016790A was added at the initial stage of culture and the cells were treated for 2 hours and the culture was continued for 3 days. The 3-day group was treated with the agonist GSK1016790A for 3 days. The blank control group did not undergo any treatment. The TRPV4 protein expression and axon regeneration related protein expression were examined by western blot assay. TUJ1 and TRPV4 immunofluorescence staining was performed simultaneously. Number of axon branches, length of axon regeneration, and number of cell survival were counted. RESULTS AND CONCLUSION: (1) Compared with the blank control group, there was no significant difference in TRPV4 protein changes after GSK101 stimulated nerve cells for 2 hours (P > 0.05); while the expression of TRPV4 decreased significantly after nerve cells were stimulated for 3 days (P < 0.05). (2) Compared with the blank control group, after GSK1016790A stimulated nerve cells for 2 hours, there was no significant difference in the number of axon branches and axon length (P > 0.05); after stimulating nerve cells for 3 days, the number of axon bifurcations and axon length were increased significantly (P < 0.05). (3) Compared with the blank control group, there was no significant change in cell survival rate after GSK1016790A stimulated nerve cells for 2 hours or 3 days. (4) Compared with the blank control group, after GSK1016790A stimulated nerve cells for 3 days, the expression of PTEN decreased (P < 0.05), and the regeneration of nerve axons was significant. This process may be mediated by inhibiting the expression of PTEN protein. [ABSTRACT FROM AUTHOR]

Copyright of China Surfactant Detergent & Cosmetics (1001-1803) is the property of China Surfactant Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Synovitis is one of the main pathological features of knee osteoarthritis. Previous studies have shown that acupuncture has a significant effect on knee osteoarthritis. Whether acupuncture can relieve the symptoms by regulating the related proteins in synovium is worthy of further study. OBJECTIVE: To investigate the effects of acupuncture combined with moxibustion on circadian clock proteins (Clock, Bmal1), TRPV4, and interleukin-1β in the synovium of rats with osteoarthritis. METHODS: Eighty 3-month-old male Sprague-Dawley rats were randomly divided into four groups: control group, model group, acupuncture group and acupuncture combined with moxibustion group (n=20 per group). Rat models of osteoarthritis were prepared by surgery in the latter three groups. Rats in the acupuncture group were treated with manual acupuncture at Zusanli (ST36), Dubi (ST35), and Neixiyan (EX-LE5) acupoints on the 7th day of modeling, at a depth of 5 mm, 15 minutes once a day, totally for 21 days. Rats in the acupuncture combined with moxibustion group were treated with acupuncture (same as that in the acupuncture group) combined with moxibustion. After corresponding treatments, the spontaneous activity ability of the rats was measured by an open field test. The pathological structure of the synovium was observed by hematoxylin-eosin staining. The expression of Clock, Bmal1 and transient receptor potential vanilloid 4 (TRPV4) in the synovium was detected by western blot. The expression of interleukin-1β in the synovium was detected by immunofluorescence labeling. RESULTS AND CONCLUSION: Compared with the control group, the expression of Clock and Bmal1 in the synovium was significantly decreased (P< 0.01), the levels of interleukin-1β and TRPV4 in the synovium were significantly increased (P < 0.05), and moreover severer loss of synovial epithelium was observed in the model group. Compared with the model group, acupuncture and acupuncture combined with moxibustion could significantly improve the spontaneous activity ability of the rats, increase the expression of Clock and Bmal1 (P < 0.05), decrease the levels of interleukin-1β and TRPV4 in the rat synovium (P< 0.05), and relieve the loss of synovial epithelium. Compared with the acupuncture group, these changes were more obvious in the acupuncture combined with moxibustion group (P < 0.05). To conclude, relative to acupuncture alone, acupuncture combined with moxibustion can effectively regulate arthritic injury in knee osteoarthritis rats, reduce the expression of TRPV4 in synovial cells, promote the expression of Clock and Bmal1 in the synovium, thereby regulating the circadian clock in synovial cells, reducing the expression of inflammatory factors and slowing the degeneration of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Copyright of China Surfactant Detergent & Cosmetics (1001-1803) is the property of China Surfactant Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Guangdong University of Technology is the property of Journal of Guangdong University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.

The intracellular signaling molecules and membrane ion channels regulate the sperm function. The transient receptor potential (TRP) channels participate in various physiological processes through regulating the intracellular ion concentrations. The thermo-TRP channels are a group of the TRP channels which can convert the temperature signal into biological signal, including the heat-gated ion channels such as TRPV1, TRPV2, TRPV3 and TRPV4, and the cold-gated ion channels such as TRPM8 and TRPA1. TRPM8 and TRPV1 located in the different segments of the sperm are involved in calcium signaling pathway. The activated TRPM8 and TRPV1 can regulate sperm motility, acrosome reaction, thermotaxis, etc. TRPV1 can also induce sperm to release from oviductal epithelia cell adhesion. Besides, the change of TRPV1 ligand binding sites can lead to the dysfunction of TRPV1 channel, which might have negative effects on male fertility. [ABSTRACT FROM AUTHOR]

Objective To explore the effect and regulatory mechanism of transient receptor potential vanilloid 1 (TRPV1)receptor on M2 macrophages phenotypes. Methods THP-1 cells were induced into M2 macrophages by IL-4 on March of 2016，with specific TRPV1 receptor agonists and blockers respectively，to investigate the effects of TRPV1 on phenotypic correlation indicators of M2 macrophages. The ELISA was adopted to detect the secretion of TGF-β，while the RT-PCR was applied to determine the expression of mRNA. Results The expression of phenotypic correlation indicators of M2 macrophages induced by IL-4 increased obviously，and the difference had statistical significance(P<0.05)；the expression of phenotypic correlation indicators decreased remarkably after activating TRPV1 receptors，while the expression was inhibited after blocking TRPV1. Conclusion The TRPV1 receptor can inhibit inflammatory response and protect the body by regulating the phenotypic correlation indicators of M2 macrophages. [ABSTRACT FROM AUTHOR]

Objectives: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1., Methods: Male SD rats were randomly divided into 6 groups ( n =8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence., Results: The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P <0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P <0.01), and they were decreased after WSP and SASP treatment (all P <0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P <0.01), and it was decreased after WSP and SASP treatment., Conclusions: WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

PURPOSE: To investigate the expression of TRPVI and IL-1α in Sprague-Dawley rats'periodontal ligament (PLD) during experimental tooth movement of different orthodontic force and duration, and explore the role of TRPV1 and IL-1α in orthodontic pain. METHODS: 66 Sprague-Dawley rats were divided into control group (n=6),sham operation group (n=6) and experimental group (n=54) randomly. Orthodontic force was applied on right first maxillary molar in rats and the changes of TRPV1 and IL-α expression were detected by real-time PCR at 4 h, 8 h, 1 d (three subgroups were added according to different forces: 1 d-30 g, 1 d-50 g, 1 d-80 g ), 3 d, 5 d, 7 d, 14 d after tooth movement. The data was analyzed using SPSS 13.0 software pakage. RESULTS: Following the experimental tooth movement, the expression of TRPVI and IL-1α in periodontal tissues were significantly up-regulated from 4 h to 7 d, with a peak at 1 d and returned to normal level at 1 week. The greater force applied during experimental tooth movement at 1 d, the higher expression of TRPVI and IL-1α were detected in periodontal tissues. CONCLUSIONS: Experimental tooth movement leads to regular change of TRPV1 and IL-1α expression in periodontal tissues, which indicates that TRPV1 and IL-1α may play an important role in orthodontic pain. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effects of transient receptor potential vanilloid type 4 (TRPV4) activation on the function and endothelial-to-mesenchymal transition (EndMT) of human umbilical vein endothelial cells (HUVECs), as well as to explore the effects of TRPV4 activation on blood perfusion and survival of rat perforator flap and the mechanism. Methods: The experimental research methods were used. The 3 rd to 6 th passages of HUVECs were used for experiments and divided into 0.5 μmol/L 4α-phorbol 12, 13-didecanoate (4αPDD) group, 1.0 μmol/L 4αPDD group, 3.0 μmol/L 4αPDD group, 10.0 μmol/L 4αPDD group, and phosphate buffer solution (PBS) group, which were cultivated in corresponding final molarity of 4αPDD and PBS, respectively. The cell proliferation activity at 6 and 12 h of culture was detected using cell counting kit-8 (CCK-8). Another batch of cells was acquired and divided into PBS group, 1 μmol/L 4αPDD group, and 3 μmol/L 4αPDD group, which were treated similarly as described before and then detected for cell proliferation activity at 6, 12, 24, and 48 h of culture. The residual scratch area of cells at post scratch hour (PSH) 12, 24, and 48 was detected by scratch test, and the percentage of the residual scratch area was calculated. The number of migrated cells at 24 and 48 h of culture was detected by Transwell experiment. The tube-formation assay was used to measure the number of tubular structures at 4 and 8 h of culture. The protein expressions of E-cadherin, N-cadherin, Slug, and Snail at 24 h of culture were detected by Western blotting. All the sample numbers in each group at each time point in vitro experiments were 3. A total of 36 male Sprague-Dawley rats aged 8 to 10 weeks were divided into delayed flap group, 4αPDD group, and normal saline group according to the random number table, with 12 rats in each group, and iliolumbar artery perforator flap models on the back were constructed. The flap surgical delay procedure was only performed in the rats in delayed flap group one week before the flap transfer surgery. Neither rats in 4αPDD group nor normal saline group had flap surgical delay; instead, they were intraperitoneally injected with 4αPDD and an equivalent mass of normal saline, respectively, at 10 min before, 24 h after, and 48 h after the surgery. The general state of flap was observed on post surgery day (PSD) 0 (immediately), 1, 4, and 7. The flap survival rates were assessed on PSD 7. The flap blood perfusion was detected by laser speckle contrast imaging technique on PSD 1, 4, and 7. The microvascular density in the flap's choke vessel zone was detected by immunohistochemical staining. All the sample numbers in each group at each time point in vivo experiments were 12. Data were statistically analyzed with analysis of variance for factorial design, analysis of variance for repeated measurement, one-way analysis of variance, least significant difference t test, and Bonferroni correction. Results: At 6 and 12 h of culture, there were no statistically significant differences in cell proliferation activity in the overall comparison among PBS group, 0.5 μmol/L 4αPDD group, 1.0 μmol/L 4αPDD group, 3.0 μmol/L 4αPDD group, and 10.0 μmol/L 4αPDD group ( P >0.05). At 6, 12, 24, and 48 h of culture, there were no statistically significant differences in cell proliferation activity in the overall comparison among PBS group, 1 μmol/L 4αPDD group, and 3 μmol/L 4αPDD group ( P >0.05). At PSH 12, the percentages of the residual scratch area of cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were close to that in PBS group ( P >0.05). At PSH 24 and 48, compared with those in PBS group, the percentages of the residual scratch area of cells in 3 μmol/L 4αPDD group were significantly decreased (with t values of 2.83 and 2.79, respectively, P <0.05), while the percentages of the residual scratch area of cells in 1 μmol/L 4αPDD group showed no significant differences ( P >0.05). At 24 h of culture, the number of migrated cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were close to that in PBS group ( P >0.05). At 48 h of culture, the number of migrated cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD groups were significantly greater than that in PBS group (with t values of 6.20 and 9.59, respectively, P <0.01). At 4 h of culture, the numbers of tubular structures of cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were significantly greater than that in PBS group (with t values of 4.68 and 4.95, respectively, P <0.05 or <0.01). At 8 h of culture, the numbers of tubular structures of cells in 1 μmol/L 4αPDD and 3 μmol/L 4αPDD groups were similar to that in PBS group ( P >0.05). At 24 h of culture, compared with those in PBS group, the protein expression level of E-cadherin of cells in 3 μmol/L 4αPDD group was significantly decreased ( t =5.13, P <0.01), whereas there was no statistically significant difference in the protein expression level of E-cadherin of cells in 1 μmol/L 4αPDD group ( P >0.05); the protein expression level of N-cadherin of cells in 3 μmol/L 4αPDD group was significantly increased ( t =4.93, P <0.01), whereas there was no statistically significant difference in the protein expression level of N-cadherin of cells in 1 μmol/L 4αPDD group ( P >0.05); the protein expression levels of Slug of cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were significantly increased (with t values of 3.85 and 6.52, respectively, P <0.05 or P <0.01); and the protein expression level of Snail of cells in 3 μmol/L 4αPDD group was significantly increased ( t =4.08, P <0.05), whereas there was no statistically significant difference in the protein expression level of Snail of cells in 1 μmol/L 4αPDD group ( P >0.05). There were no statistically significant differences in the protein expression levels of E-cadherin, N-cadherin, Slug, or Snail of cells between 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group ( P >0.05). The general condition of flaps of rats in the three groups was good on PSD 0. On PSD 1, the flaps of rats in the three groups were basically similar, with bruising and swelling at the distal end. On PSD 4, the swelling of flaps of rats in the three groups subsided, and the distal end turned dark brown and necrosis occurred, with the area of necrosis in flaps of rats in normal saline group being larger than the areas in 4αPDD group and delayed flap group. On PSD 7, the necrotic areas of flaps of rats in the 3 groups were fairly stable, with the area of necrosis at the distal end of flap of rats in delayed flap group being the smallest. On PSD 7, the flap survival rates of rats in 4αPDD group ((80±13)%) and delayed flap group ((87±9)%) were similar ( P >0.05), and both were significantly higher than (70±11)% in normal saline group (with t values of 2.24 and 3.65, respectively, P <0.05 or P <0.01). On PSD 1, the overall blood perfusion signals of rats in the 3 groups were basically the same, and the blood perfusion signals in the choke vessel zone were relatively strong, with a certain degree of underperfusion at the distal end. On PSD 4, the boundary between the surviving and necrotic areas of flaps of rats in the 3 groups became evident, and the blood perfusion signals in the choke vessel zone were improved, with the normal saline group's distal hypoperfused area of flap being larger than the areas in delayed flap group and 4αPDD group. On PSD 7, the blood perfusion signals of overall flap of rats had generally stabilized in the 3 groups, with the intensity of blood perfusion signal in the choke vessel zone and overall flap of rats in delayed flap group and 4αPDD group being significantly greater than that in normal saline group. On PSD 7, the microvascular density in the choke vessel zone of flap of rats in 4αPDD group and delayed flap group were similar ( P >0.05), and both were significantly higher than that in normal saline group (with t values of 4.11 and 5.38, respectively, P <0.01). Conclusions: After activation, TRPV4 may promote the migration and tubular formation of human vascular endothelial cells via the EndMT pathway, leading to the enhanced blood perfusion of perforator flap and microvascular density in the choke vessel zone, and therefore increase the flap survival rate.

Atrial Ca 2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca 2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca 2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca 2+ transient duration (CaD), alternan, and the recovery properties of Ca 2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca 2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca 2+ -RyR pathway, and thus exerts therapeutic effect on POAF.

To observe the efficacy of San'ao Decoction(SAD) in diffusing the lung and relieving asthma, and its intervention effect on the expression of transient receptor potential V2(TRPV2) during alleviating asthma, this study replicated an ovalbumin(OVA)-induced asthmatic mice model, and investigated the intervention effect of SAD on the airway inflammation and airway hyperresponsiveness. The regulatory mechanisms of SAD on the mRNA and protein expressions of TRPV2 in lung tissues and the levels of interleukin-4(IL-4),-10(IL-10), nerve growth factor(NGF), prostaglandin D&#95;2(PGD&#95;2) in bronchoalveolar lavage fluid(BALF) were discussed. Compared with the control group, the model group showed typical asthmatic phenotype, the level of eosinophils(EOS) in peripheral blood and BALF as well as the airway hyperresponsiveness were increased(P&lt;0.01), and pathological damage in lung tissue was serious. The mRNA and protein expressions of TRPV2 in lung tissue were increased significantly, while the levels of IL-4, IL-10, NGF and PGD&#95;2 in BALF were elevated(P&lt;0.05,P&lt;0.01). SAD could relieve bronchial asthma manifested as repaired lung patholo-gical changes(P&lt;0.05), reduce the level of EOS in blood and BALF(P&lt;0.05, P&lt;0.01), and improve pulmonary resistance and lung compliance(P&lt;0.05, P&lt;0.01). SAD could also regulate the inflammatory cytokine levels of IL-4, IL-10, NGF, PGD&#95;2 in BALF, and reduce the gene and protein expression of TRPV2 in the lung tissue(P&lt;0.05, P&lt;0.01). It is verified that SAD could reduce the lung inflammation, and improve lung function in asthmatic mice. The regulatory mechanism of SAD on asthma induced by OVA might be related to the regulation of TRPV2 expression and the induced decrease of Th2-related cytokines and neuropeptides, which provides the evidences for the treatment of asthma with SAD.

Protein kinase Cε (PKCε) is a transforming oncogene and plays an important role in many cellular processing. In the present paper, we review the development of experimental researches on the acute-chronic pain transformation. Results indicated that prostaglandin E2 (PGE2) / EP1 receptor-Gq-PKCε is an important signaling pathway to modulate chronic pain in peripheral dorsal root ganglion (DRG) neurons, and also plays a role in the later stage of hyperalgesia during transformation from acute to chronic pain. PKCε in DRG neurons induces mechanical and thermal hypersensitivity respectively by over expression of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin-1 (TRPA1), further mediating the transformation from acute to chronic pain. Whereas, PGE2-evoked activation of EP1-Gq-PKCε signaling may be the key link in initiating the pain translation process through regulating downstream TRPA1 and TRPV1. Electroacupuncture (EA) has been used to effectively relieving various types of acute and chronic pain for decades, and can significantly inhibit the expression of PKCε and its upstream and downstream molecules. Therefore, it can be inferred that there exists a possibility of EA interventions in interfering the transformation from acute to chronic pain by regulating peripheral PKCε signaling pathway.

Objective: With the aid of an acute visceral pain model of uterine cervical distension (UCD), the present study aimed to observe the effects of intrathecal administration of transient receptor potential vanilloid 1 (TRPV1) antagonist SB-366791 on UCD induced-visceral nociception as well as its involved molecular mechanisms. Methods: A total of 30 Sprague-Dawley-derived adult virgin female rats were used. UCD model was established under isoflurane inhalation anesthesia. Briefly, a lower abdominal incision at midline was made to expose the uteral cervix, two metal rods were inserted through both sides of the cervix separately, one rod was fixed and the other one was connected to a pulley system with application of manual weighted traction (0, 25, 50, 75 or 100 g) for simulating 1 h of cervical distension. In addition, 12 Sprague-Dawley-derived adult virgin female rats were subjected to intrathecal catheter implantation, and UCD was established 7 days later. The rats were divided randomly into two groups; one group was administrated with intrathecal SB-366791 while the other was administrated with the same volume of saline as control. The 75 g distension force was then applied for an hour and the electromyographic (EMG) of musculus rectus abdominis, heart rate as well as respiratory frequency were measured continuously during the surgery. The spinal cord (T(12)-L(2)) was collected 30 minutes after UCD for the detection of changes of c-FOS and TRPV1 expression. Results: UCD increased EMG activity ( P< 0.05) and c-FOS expression ( P< 0.05) in the deep dorsal horn region and central canal of the spinal cord (T(12)-L(2)) in a stimuli-dependent manner, the expression of TRPV1 in the T(12)-L(2) spinal cord also increased in response to UCD stimulation ( P< 0.05). Compared with the saline group, intrathecal SB-366791 significantly decreased EMG activity ( P< 0.05) as well as spinal c-FOS ( P< 0.05) expression induced by UCD. Conclusions: UCD in rats increases EMG activity of musculus rectus abdominis as well as spinal c-FOS and TRPV1 expression. Intrathecal administration of TRPV1 antagonist SB-366791 significantly decreases the visceral nociception induced by UCD.

Objective: To discuss the effect of chronic restraint stress (CRS) on esophageal hypersensitivity and inflammation, as well as the impact of oxidative stress in a murine model. Methods: 20 male SPF mice were randomly divided into two groups, CRS and normal control(NC) group. Then the mice in CRS group were submitted to 2 h per day of restraint stress for a period of 14 days. For the rest of the time, mice in both groups were given free drinking and eating in the same environment. Histopathological changes of esophageal tissue were observed using HE staining and analyzed by histological damaging score. The esophageal expression levels of transient receptor potential vanilloid (TRPV-1) and nicotinamide adenine dinucleotide phosphate oxidase 4(NOX-4) were detected by immunohistochemical staining. Further more, protein expression level of TRPV-1 was also observed by Western blotting. In addition, mRNA expression levels of TRPV-1, oxidant/antioxidant enzymes and related cytokines in esophageal tissues were detected by real time PCR. Results: HE staining for esophageal tissues revealed that histopathological changes including basal cell hyperplasia, infiltration of neutrophils and plasmocytes were observed in stressed mice, while there was no distinct changes observed in non-stressed mice. Histological damaging scores for epithelial damage and submucosal inflammatory cells were higher in CRS group, and the differences were statistically significant(all P< 0.05). Immunohistochemical staining revealed that positive cells for TRPV-1 and NOX-4 were observed in majority of samples, but the number of positive cells and density were higher in CRS mice. Western blotting showed that the expression levels of TRPV-1 protein in CRS mice was higher than that of NC mice (1.0±0.0 vs 1.6±0.2; t= -7.06, P< 0.001). RT-PCR showed that mRNA expression levels of TRPV1 and NOX-4 in CRS group were higher than those in NC group (1.0±0.0 vs 2.0±0.2, 1.0±0.0 vs 2.0±0.2; t= -13.44, -14.32, all P< 0.001). Moreover, mRNA expression levels of antioxidant enzymes, such as Mn-SOD and Cu Zn-SOD, were higher in stressed mice (1.0±0.0 vs 0.7±0.1, 1.0±0.0 vs 0.7±0.1), and the differences were statistically significant ( t= 8.39,7.36, all P< 0.05). The mRNA expression levels of important cytokines, such as MCP-1, IL-8, TNF-α, in stressed mice were overexpressed comparing to non-stressed mice (1.0±0.0 vs 2.4±0.4, 1.0±0.0 vs 1.8±0.2, 1.0±0.0 vs 2.5±0.4), and the differences were statistically significant ( t= -10.06, -13.24, -12.40, all P< 0.001). Conclusions: Chronic stress may result in esophageal hypersensitivity through activation of TRPV1, and may also cause esophageal inflammation. Stress-induced oxidative stress may contribute to the formation of esophageal hypersensitivity.

Objective: To compare the effects of electroacupuncture (EA) at "Dachangshu" (BL 25) or "Tianshu" (ST 25) for visceral sensitivity, gene expression product c-kit of colonic Cajal interstitial cells (ICC) and capsaicin receptor 1 (TRPV1) of irritable bowel syndrome (IBS) rats, so as to investigate the effect and mechanism differences of EA at the back shu point and the front mu point of large intestine for IBS rats., Methods: Forty-two Wistar neonatal rats were randomly divided into a blank group (9 rats) and a model group (33 rats). IBS model was established with mother and child separation, acetic acid enema in young rats and colorectal dilatation method. Twenty-seven IBS rats in life were randomly divided into a model control group, a Dachangshu group and a Tianshu group, 9 rats in each group. EA (disperse-dense wave, 2 Hz/100 Hz, 0.1-0.3 mA) for 20 min was used at "Dachangshu" (BL 25) and "Tianshu" (ST 25) respectively in the Dachangshu and Tianshu groups, once every other day, totally 5 times. The rats in the model control group were fixed with soft cloth sleeve for 20 min, without acupuncture. No intervention was used in the blank group. The stool property Bristol grading score was recorded before and after intervention in each group. The visceral sensitivity was evaluated by abdominal withdrawal reflex. The latency until the first systolic wave occurred and the number of systolic wave within 90 s were observed. Immunohistochemical was used to detect the positive expressions of c-kit and TRPV1, the ICC colon specific marker., Results: Compared with the blank group, the Bristol score increased，latency period shortened, systolic wave number increased, c-kit and TRPV1 positive expressions increased in the model control group (all P <0.01). Compared with the model control group, the Bristol score decreased, latency period increased, systolic wave number decreased, c-kit and TRPV1 positive expressions decreased after intervention in the Dachangshu and Tianshu groups ( P <0.05, P <0.01). Compared with the Dachangshu group, the TRPV1 positive expression decreased after intervention in the Tianshu group ( P <0.05)., Conclusion: EA at "Dachangshu" (BL 25) or "Tianshu"(ST 25) can improve the diarrhea in IBS model rats, reduce the visceral sensitivity, and its mechanism may be related to regulating the expressions of colon c-kit and TRPV1. EA at "Tianshu" (ST 25) is more apparent for TRPV1 than at "Dachangshu" (BL 25).

Objective: To investigate the effects and mechanisms of anthocyanin from Ligustrum vicaryi on chronic inflammatory pain induced by complete Freund's adjuvant., Methods: Thirty male SD rats were randomly divided into three groups ( n =10):normal saline control group (NS), chronic inflammatory pain model group(Mod, injected with complete Freund's adjuvant(CFA) 100 μl to the left hind leg), anthocyanin treatment group(Ant, dosed with anthocyanins (90 m), mechanical pain threshold (MPT), and left toe volume in each group were measured before modeling and 1,3,5,7,9,11,13 days after operation. Antioxidant indexes in serum were mensurated by spectrophotometer, and the total capsaicin receptor (TRPV1) and phosphorylated capsaicin receptor (p-TRPV1) in hippocampus were detected by Western blot., Results: In comparison with controls, HPT and MPT were improved ( P <0.05),toe swelling was reduced( P <0.05), the serum level of SOD was increased ( P <0.01), while the levels of MDA and NO were decreased ( P <0.05), the ratio of P-TRPV1/TRPV1 protein was depressed in Mod rat hippocampal region treated with anthocyanin., Conclusions: The results show that anthocyanins has an analgesic effect on chronic inflammatory pain induced by CFA, and its mechanism may be related to the improvement of antioxidant capacity and the reduction of TRPV1 phosphorylation.

Objective: To observe the effect of the expressive or functional blockage of TRPV1 on nerve regeneration after sciatic trans-section injury. Methods: AMG-517, a kind of TRPV1 inhibitor, was injected into the surrounding area of the ipsilateral lumbar dorsal root ganglia while unilateral sciatic nerve was transected. A total of 24 healthy male Sprague-Dawley rats were divided into 4 groups: control group, injury only group, injury+ AMG-517 150 μg/kg group, injury+ AMG-517 300 μg/kg group. The injury only group was injected the same volume of medium. The release of CGRP from dorsal-horn of spinal cord, the number of axons at proximal stem of sciatic nerve after transection, and the expression of TRPV1 in dorsal root ganglion were detected using the methods of ELISA, Western blot and semi-thin section (1 μm)- toluidine blue staining 2 weeks after injury. Results: The release of CGRP in lumbar spinal dorsal horn was obviously decreased after AMG-517 treatment, which was the evidence of TRPV1 functional inhibition. CGRP in the control group was 0.15 ng/g, the injury only group 0.17 ng/g, AMG-517 150 μg/kg group 0.09 ng/g, and AMG-517 300 μg/kg group 0.11 ng/g( P <0.01). The number of axons which were myelinated or unmyelinated increased after the TRPV1 was inhibited by AMG-517( P <0.01). In addition, the injection of AMG-517 into surrounding dorsal root ganglion decreased the expression of TRPV1 in dorsal root ganglion( P <0.01). Conclusions: Over expression or activation of TRPV1 after periphery nerve injury has negative effect on nerve regeneration in fact; Inhibiting the over-expression or over-activation of TRPV1 after nerve injury facilitates axonal regeneration and nerve repair.

Purpose: Sprague-Dawley rat models of tooth movement were established to investigate the expression of transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene related peptide (CGRP) in rat trigeminal ganglion during orthodontic tooth movement, and to explore the roles of TRPV1 and CGRP in orthodontic pain., Methods: Sixty-six Sprague-Dawley rats were randomly divided into control group (n=6), sham operation group (n=6), and experimental group (n=54). Tooth movement models were established, orthodontic force (50 g) was applied on the maxillary first molar in the rats of experimental group, and then the trigeminal ganglia were collected at 4, 8 h, 1 d (3 subgroups were set up according to the force: 1 d-30 g, 1 d-50 g, 1 d-80 g), 3, 5, 7, 14 d after tooth movement. The changes of TRPV1 and CGRP expression were detected by immunofluorescence staining. SPSS16.0 software package was used for statistical analysis., Results: According to immunofluorescence staining, the TRPV1-IR and CGRP-IR neurons were mostly small to medium sized. The percentages of TRPV1-IR and CGRP-IR neurons in trigeminal ganglion increased after applying force, and reached the peak at 1-3 d and then fell to the initial level gradually. In addition, the application of greater force during experimental tooth movement induced higher percentages of TRPV1-IR and CGRP-IR neurons in trigeminal ganglion., Conclusions: Experimental tooth movement leads to the regular changes of TRPV1-IR and CGRP-IR neurons in trigeminal ganglion, indicating that TRPV1 and CGRP may play important roles in orthodontic pain.

Purpose: To investigate the expression of TRPV1 and IL-1α in Sprague-Dawley rats' periodontal ligament (PLD) during experimental tooth movement of different orthodontic force and duration, and explore the role of TRPV1 and IL-1α in orthodontic pain., Methods: 66 Sprague-Dawley rats were divided into control group (n=6), sham operation group (n=6) and experimental group (n=54) randomly. Orthodontic force was applied on right first maxillary molar in rats and the changes of TRPV1 and IL-1α expression were detected by real-time PCR at 4 h, 8 h, 1 d (three subgroups were added according to different forces: 1 d-30 g, 1 d-50 g, 1 d-80 g ), 3 d, 5 d, 7 d, 14 d after tooth movement. The data was analyzed using SPSS 13.0 software pakage., Results: Following the experimental tooth movement, the expression of TRPV1 and IL-1α in periodontal tissues were significantly up-regulated from 4 h to 7 d, with a peak at 1 d and returned to normal level at 1 week. The greater force applied during experimental tooth movement at 1 d, the higher expression of TRPV1 and IL-1α were detected in periodontal tissues., Conclusions: Experimental tooth movement leads to regular change of TRPV1 and IL-1α expression in periodontal tissues, which indicates that TRPV1 and IL-1α may play an important role in orthodontic pain.

This paper was designed in middle cerebral artery occlusion (MCAO) model of rats, to explore the role of transient receptor potential channel 4 (TRPC4) as Ca(2+) selective channel by detecting the changes of the expression of TRPC4 in different parts of cerebral tissues under the condition of focal cerebral ischemia. The rats were sacrificed after MCAO surviving time 6 h, 12 h, 1 d, 3 d. As determined by Western blot, the expressions of TRPC4 in striatum and hippocampus of 12 h, 1 d, 3 d groups were significant higher than that in the control group (P<0.05). Immunohistochemical staining showed that the TRPC4 immunoreactive substances were present in the membrane of neurons. Compared with the control group, immunostaining positive cells increased in hippocampus and striatum of cerebral ischemia groups. The TRPC4 immunostaining positive cells increased significantly in 1d-group and 3d-group (P<0.05). It suggests that as a Ca(2+) selective channel, the variance of the expression of TRPC4 may play a role in acute and delayed neuronal injury in focal cerebral ischemia.