TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model

The objective of this study was to investigate the regulatory effects of TGF-β1 on CCL3/4 expression and inflammation-related pain during intervertebral disc degeneration (IVDD). TGF-β1 and CCL3/4 expression patterns in different degenerative human nucleus pulposus (NP) tissues were measured by qPCR and immunohistochemistry (IHC), and the effects of TGF-β1 on CCL3/4 expression were measured by qPCR, ELISA and immunofluorescence. The roles of NF-κB and MAPK in TGF-β1-mediated CCL3/4 promoter activity were studied using siRNAs, western blotting and qPCR. After establishing an IVDD rat model in vivo, we administered intradiscal injections of TGF-β1. The effects of TGF-β1 on IVDD were determined by MRI and histological analyses, and the effects of TGF-β1 on dorsal root ganglion (DRG) inflammation and pain development were determined by IHC staining and pain-behavior testing, respectively. TGF-β1 and CCL3/4 expression was elevated in degenerative NP tissue. CCL4 expression was significantly inhibited by TGF-β1 treatment. Pharmacological inhibition or siRNA knockdown of the ERK1/2 signaling attenuated TGF-β1-mediated suppression of CCL4 expression. In vivo, TGF-β1 injection inhibited the development of degenerative features in the IVDD model. Moreover, TGF-β1 prevented the inflammatory response and pain development. The results of this study show that TGF-β1 downregulates CCL4 expression through ERK1/2 signaling activation in NP cells. Furthermore, TGF-β1 can prevent degenerative processes, inhibit inflammatory responses in the DRG and prevent pain development in the IVDD rat model. The results of this study indicate that TGF-β1 may represent a therapeutic target for the control of inflammation-related pain associated with IVDD.

Surveillance of schistosomiasis japonica in potential endemic areas in Hubei Province from 2008 to 2012 / 中国血吸虫病防治杂志

Objective To explore the potential key risk factors of schistosomiasis transmission in potential endemic areas so as to provide the evidence for setting up the prediction and surveillance systems of schistosomiasis outbreak epidemic. Methods From 2008 to 2012,fixed and mobile surveillance sites in potential endemic areas of 2 counties in Hubei Province were selected. The immunological assays and stool examinations were carried out to investigate the schistosome infection situation of local people, mobile population and livestock. The distribution of Oncomelania hupensis snails was investigated in risk areas and suspicious ar-eas,and spreading patterns of snails were observed in the rivers that directly connected with the Yangtze River. Results A total of 6 052 local people aged 6-65 years were screened by IHA immunological tests,and the positive rate of antibody was 1.19%(72/6 052). Totally 72 antibody positives were examined by Kato-Katz technique and there were no positives. A total of 5 004 mo-bile persons were tested by IHA immunological tests and the positive rate was 1.36%(68/5 004). Totally 68 antibody positives were examined by Kato-Katz technique and there were no positives. Totally 287.07 hm2 potential endemic areas were investigated for Oncomelania snail detection,and no snails were found. The investigation on snail spreading patterns and the surveillance on suspicious circumstances were carried out,with no snails found. Conclusions In the schistosomiasis potential endemic areas, some positives of IHA immunological tests are found. Therefore,monitoring is still needed to be strengthened.

Molluscicidal effect comparison between TDS and MNSC in field / 中国血吸虫病防治杂志

Objective To compare the molluscicidal effects between“Luo-wei”(TDS),a plant molluscicide in 4 percent, and metaldehyde and niclosamide(MNSC)in the field. Methods A natural ecological environment with Oncomelania hupensis was selected as the test area,the test concentrations of TDS and MNSC were 2.5 g/m3 and 2 ml/m3 respectively by the immersion method;the test doses of TDS and MNSC were 3 g/m2 and 2 ml/m2 respectively by the spray method;the doses of WPN in a control group were 2 g/m3 and 2 g/m2 respectively by the two methods above-mentioned. The molluscicidal effects between TDS and MNSC were compared by using the synchronous design method and parallel comparative method. Results In the TDS group,the death rate of snails was 90.70%by immersion for 24 hours,reached to 81.40%after spraying for 7 days,and there were no significant differences among the observation time points in molluscicidal effects(P>0.05). One day after the spraying,the death rate of snails was less in the TDS group compared with that in the MSCN group(P0.05). In the MSCN group,the death rate of snails was 99.17%by immersion for 24 hours,reached to 66.07% by spraying for 1 day. In the WPS group,the death rate of snails was 97.15% by immersion for 24 hours,reached to 71.43%after spraying for 1 day,and there were no significant differences(both P>0.05). Conclusion TDS has a good molluscicidal activity and stable efficacy,and the molluscicidal effect of TDS is similar to that of MSCN in the filed, but the molluscicidal sensitivity of TDS is lower than that of MSCN.

Effects of invigorating Qi and promoting blood circulation drugs combined with compound triamcinolone acetonide on interleukin 2 and tumor necrosis factor in patients With oral lichen planus / 国际中医中药杂志

Objective To observe the effects of invigorating qi and promoting blood circulation drugs combined with compound triamcinolone acetonide on the interleukin 2 and tumor necrosis factor in patients with oral lichen planus. Methods 43 patients with oral lichen planus were randomly recurited into two groups by means of random number table.The control group was treated with prednisone orally, 30 mg/d, then reduced to IS mg/d at first two weeks, and further reduced to S mg/d at first three weeks. Maintained the dose for four to eight weeks. While the treatment group was treated with 40 mg compound triamcinolone acetonide at injury area by local injection,which was mixed with 2% lidocaine hydrochloride injection, once a week, continuous therapy for 2 months. Qi regulating and blood activating drugs were also added to the treatment group, with 150ml each time, once a day for 2 months. The clinical symptoms were observed, serum interleukin 2 and tumor necrosis factor were detected before and after the treatment. Results Compared with the control group, serum interleukin 2 and tumor necrosis factor in the treatment group decreased significantly after treatment [IL-2 (2.58± 0.32)ug/L, TNF(156.45+13.67)ng/L,P＜0.05]. Serum interleukin 2 and tumor necrosis factor decreased significantly after the treatment in the control group [IL-2(5.21±0.53) μg/L, TNF (205.02±15.75) ng/L,P＜ 0.05]. The total effective rate of the treatment group and the control group was 86.4% and 66.7% respectively, there was a significant difference (x2=3.321,P＜0.05).Conclusion Invigorating qi and promoting blood circulation drugs combined with compound triamcinolone acetonide on oral lichen planus was better than prednisone.

Naringin Inhibits Neuropathic Pain Produced by Lumbar 5 Spinal Nerve Ligation / 中山大学学报(医学科学版)

[Objective] To investigate the effect of naringin at different doses on the neuropathie pain produced by lumbar 5 spinal nerve ligafion (L5 SNL). [Methods] Using the method of behavioral test, we tested the 50% paw withdrawal threshold before and after intragastrieal application of naringin in the rats with L5 SNL. [Results] Naringin at 30, 90, 100 mg/kg but not at 10 mg/kg increased the 50% paw withdrawal threshold of 1.5 SNL rats significantly. Single application of Naringin (at 30 or 90 mg/kg) inhibited mechanical allodynia for around 6 hours, and the inhibitory effect persisted for 4 days after the cessation of the drug when naringin (30 mg/kg, daily) was consecutively applied for 7 days. [Conclusion] Intragastrical of naringin could relieve the neuropathic pain produced by peripheral nerve injury.

Surveillance of schistosomiasis in areas along water transfer project from Yangzte River to Hanjiang River in Qianjiang basin / 中国血吸虫病防治杂志

Objective To evaluate the impact of the water transfer project from the Yangtze River to the Hanjiang River on the transmission of schistosomiasis.so as to provide scientific basis for the development of control strategy.Methods A field investigation on snail status,the infection situation of human and cattle as well as related endemic factors was performed in the project areas of the Qianjiang basin.Results There were 33 endemic villages and 48 non-endemic villages along the water transfer project.In endemic villages,the infection rates of human and cattle were 0.42% and 0.48%,respectively.In the endemic area,the snail area was 17.28 hm~2,the mean density of living snails was 0.043 No./0.1 m~2,meanwhile,no snail Was found in the non.endemic areas.Conclusion The surveillance on epidemic situation should be carried out for a long time in order to prevent the spreading of snails.

NMDA Receptor Channels Are Involved in The Expression of Long-term Potentiation of C-fiber Evoked Field Potentials in Rat Spinal Dorsal Horn / 生物化学与生物物理进展

In hippocampus, numerous studies have shown that N-methyl-D-aspartate (NMDA) receptors are essential for the initiation of long-term potentiation (LTP), whereas the expression of LTP is primarily mediated by the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the increased insertion of postsynaptic AMPA receptors. However, in recent years there is also evidence that NMDA receptor channels contribute to the expression of LTP under physiological conditions. It was examined whether NMDA receptor channels contributed to the expression of LTP of C-fiber evoked field potentials in rat spinal dorsal horn by intravenous or spinal application of NMDA receptor antagonists after the establishment of LTP. It was found that MK 801 (a non-competitive NMDA receptor antagonist) at dose of 0.1 mg/kg (iv) had no effect on the spinal LTP and at the dose of 0.5 mg/kg depressed the LTP significantly. However, the inhibitory effect of MK 801 at higher dose (1.0 mg/kg)was not different from that produced by the dose of 0.5 mg/kg. The similar inhibitory effect on spinal LTP was also observed, when MK 801 was applied locally at the recording segments of spinal cord. To confirm the above results, a competitive NMDA receptor antagonist AP V was tested. Spinal application of AP V at a concentration of 100 μmol/L produced a stronger depression than at 50 μmol/L. When the concentration of AP V increased to 200 μmol/L, no further depression was observed. These results indicate that NMDA receptor channels are involved in the expression of LTP of C-fiber evoked field potentials in the rat spinal dorsal horn.

Role of ERKⅠ/Ⅱ in the induction and maintenance of the spinal LTP / 中国病理生理杂志

AIM: The role of external-signal regulated kinaseⅠ/Ⅱ(ERKⅠ/Ⅱ) in the induction and maintenance of spinal long-term potentiation(LTP) is evaluated.METHODS: The C-fiber evoked field potentials were recorded at the superficial layers of spinal dorsal horn at the lumbar enlargement.RESULTS:(1) PD98059(100 ?mol/L) or SL327(200(?mol/L)),a selective MEK inhibitor,completely blocked LTP induction when applied at 30 min prior to tetanic stimulation.(2) PD98059 or SL327 reversed spinal LTP in a time-dependent manner.At 15 min after LTP induction,PD98059(100 ?mol/L) or SL327(200 ?mol/L) reversed LTP completely,and at 30 min after LTP induction,the inhibitory rate of spinal LTP inhibited by PD98059 or SL327 was 62.5% and 75.0%, respectively.At 1 h after LTP induction,however,the same concentration of PD98059 or SL327 did not affect the spinal LTP.CONCLUSION: Activation of ERKⅠ/Ⅱ in spinal dorsal horn may be crucial for the induction and the early-phase maintenance of LTP of C-fiber evoked field potentials.

Protein kinase C is involved in the induction and early- phase maintenance of long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn of adult rats / 中国病理生理杂志

AIM: The role of protein kinase C (PKC) in th e induction and maintenance of spinal long-term potentiation (LTP) was evaluated . METHODS: The C-fiber evoked field potentials were recorded at t he superficial layers of spinal dorsal horn at the lumbar enlargement. RESULTS: (i) Chelerythrine (200 ?mol/L) or G 6983 (100 ? mol/L), a selective PKC inhibitor, completely blocked LTP induction. (ii) Chel eryt hrine or G 6983 reversed spinal LTP in a time-dependent manner. 15 min after L TP induction, chelerythrine (200 ?mol/L) and G 6983 (100 ?mol/L) depre ssed LTP to baseline in all tested rats. The same concentration of chelerythrine and G 6983, applied at 3 h after LTP induction, did not affect LTP. CONCLUSION: PKC in spinal dorsal horn may be crucial for the ind uction and the early-phase maintenance of LTP of C-fiber evoked field potentials .

PKA is required in the induction and early-phase maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of adult rats / 中国病理生理杂志

AIM: The role of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in the induction and maintenance of spinal long-term potentiation (LTP) was evaluated. METHODS: The C-fiber evoked field potentials were recorded at the superficial layers of spinal dorsal horn at the lumbar enlargement. RESULTS: (1) 8-Br-cAMP induced LTP of C-fiber evoked field potentials and 8-Br-cAMP-induced LTP occludes tetanus-induced LTP. (2) Rp-CPT-cAMPS, an inhibitor of PKA, blocked the induction of spinal LTP and reversed established LTP of C-fiber evoked field potentials in a time-dependent manner. (3) In the presence of anisomycin, a protein synthesis inhibitor, the potentiation induced by 8-Br-cAMP was completely blocked. (4) PD98059, a selective inhibitor of mitogen-activated protein kinase (MAPK),completely blocked the 8-Br-cAMP-induced LTP.CONCLUSION: Activation of PKA signal pathway in spinal dorsal horn may be crucial for the induction and the early-phase maintenance of LTP of C-fiber evoked field potentials.