Mild moxibustion at Tianshu (ST 25) decreases expression of prokineticin-1 and prokineticin receptor-1 in colon tissue of rats with chronic visceral hyperalgesia

Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu （ST 25） decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.

Analgesic action of suspended moxibustion in rats with chronic visceral hyperalgesia correlates with enkephalins in the spinal cord

Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.

Electroacupuncture at Tianshu (ST 25) for diarrhea-predominant irritable bowel syndrome using positron emission tomography Changes in visceral sensation center

Previous studies have demonstrated that electroacupuncture therapy is effective in the treatment of irritable bowel syndrome. However, the precise mechanism of this therapy is unknown. The present study served to investigate the effects of electroacupuncture therapy on treatment of patients with diarrhea-predominant irritable bowel syndrome （IBS）. We compared brain activation maps based on the changes of cerebral glucose metabolism obtained by 18-fluorodeoxyglucose positron emission tomography scanning under three conditions： resting, rectal balloon distension and rectal balloon distension plus electroacupuncture. Under the resting condition, compared with healthy controls, IBS patients displayed an increasing regional cerebral metabolic rate of glucose over a wide range： bilateral superior temporal gyrus, right middle occipital gyrus, superior frontal gyrus and bilateral middle frontal gyrus. However, there was no significant activity in the visceral pain center. Compared with the resting condition, under the rectal balloon distension condition, patients with IBS had a greater regional cerebral metabolic rate of glucose in the prefrontal cortex, left anterior cingulate cortex, postcentral gyrus, precentral gyrus and temporal gyrus. Under the rectal balloon distension plus electroacupuncture condition, stimulation by electroacupuncture at Tianshu （ST 25） manifested a decreased regional cerebral metabolic rate of glucose in the left cingulate gyrus, right insula, right caudate nucleus, fusiform gyrus and hippocampal gyrus. Electroacupuncture therapy relieved abdominal pain, distension or discomfort by decreasing glucose metabolism in the brain.

Suspended moxibustion at Tianshu (ST25) inhibits prokineticin 1 and prokineticin receptor 1 expression in the spinal cord of rats with chronic visceral hypersensitivity

Suspended moxibustion can decrease the expression of prokineticin 1 and its receptor in colonic tissue from rats modeling chronic visceral hyperalgesia. This study aimed to verify if rat spinal cord prokineticin 1 and its receptor contribute to the analgesic effect of suspended moxibustion in a rat model of irritable bowel syndrome where rats display chronic visceral hypersensitivity. Results showed that suspended moxibustion at Tianshu （ST25） point significantly decreased visceral sensitivity to colorectal distention in a chronic visceral hyperalgesia rat model; also protein and mRNA expression of prokineticin 1 and prokineticin receptor 1 in the spinal cord of rats was significantly decreased. Experimental findings indicate that prokineticin 1 and prokineticin receptor 1 are involved in the analgesia using suspended moxibustion in rats with chronic visceral

Effects of electroacupuncture on c-Fos expression in the spinal cord and brain of rats with chronic visceral hypersensitivity

BACKGROUND： Visceral hypersensitivity is the main cause of irritable bowel syndrome, c-Fos is a marker of visceral hypersensitivity in the central nervous system. Electroacupuncture can relieve chronic visceral hypersensitivity in rats, but the mechanism is still unknown. OBJECTIVE： To identify c-Fos expression in the spinal cord and cerebral cortex of rats with chronic visceral hypersensitivity, and to test the effects of electroacupuncture on pain sensitivity in rats with chronic visceral hypersensitivity. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Animal E：~perimental Center, Shanghai University of Traditional Chinese Medicine, from January to April, 2007. MATERIALS： A total of 24 neonatal, male, Sprague Dawley rats, aged five days old, were equally and randomly assigned into a normal group, a model group, and an electroacupuncture group. Rabbit anti-rat c-Fos antibody and Evision secondary antibody kits （Sigma, USA）, diaminobenzidine kit （Dako, Denmark）, and an LD202H electroacupuncture apparatus （Huawei, Beijing, China） were used in this study. METHODS： Neonatal rats from the model and electroacupuncture groups were used to establish rat models of chronic visceral hypersensitivity by the saccule stimulation method. After model establishment, 0.25 mm diameter electric needles were inserted into Tianshu （ST 25） and Shangjuxu （ST37） at a depth of approximately 0.5 cm, with an square wave （alternating current frequency at 100/20 Hz, amplitude ranged 0.2-0.6 ms, intensity at 1 mA） once for 20 minutes, once a day, for seven days. Rats in the normal and model groups were not treated. MAIN OUTCOME MEASURES： Following 7 days of treatment, c-Fos expression in the spinal cord and cerebral cortex was detected by immunohistochemistry. After the first electroacupuncture treatment, abdominal withdrawal reflex scores were investigated to evaluate the pain threshold for chronic visceral hypersensitivity in rats. RESULTS： Visceral hypersensitivity increased c-Fos staining （P 〈 0.05）, and electroacupuncture significantly decreased the number of these cells to near normal levels （P 〉 0.05）. Abdominal withdrawal reflex scores were significantly lower in the electroacupuncture and normal groups than in the model group （P 〈 0.05） and were similar between the electroacupuncture and normal groups （P 〉 0.05）. CONCLUSION： Electroacupuncture decreases c-Fos expression in the spinal cord and cerebral cortex and increases pain threshold in a chronic visceral hypersensitivity model in rats.

Effects of moxibustion on heat-shock protein 70 expression in the spinal cord and colonic mucosa in a rat model of ulcerative colitis

Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the colonic mucosa, but the mechanisms of action remain unknown. The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70 （HSP70） and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats. Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats. The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats. Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.

Identification the main molecular mechanism of AT1R Non-desensitization

Angiotensin II Type 1 Receptor Autoantibodies(AT1-AA)as a functional receptor activator can persistently activate Angiotensin II Type 1 Receptor(AT1R)by causing AT1R non-desensitization which is one of the important pathogenesis of preeclampsia(PE).However,the molecular mechanisms of AT1-AA results AT1R non-desensitization remain unknown.In order to explore the background molecular mechanisms of AT1R non-desensitization induced by AT1-AA,we construct dynamical models which are composed of control model(based on the body of healthy pregnant women)and experimental group models(based on the body of pregnant women with PE)in this paper.We also consider the effect of membrane fluidity on the reaction when building the dynamical models.In the experiment group models,we establish two models that caused AT1R non-desensitization:endocytosis disorder model and conformational change model.We write C++and MATLAB programs to do the data fitting.By comparing the data fitting results and analyzing the images of models and corresponding Bayesian information criterion(BIC)values,we conclude that conformational changes may be the key molecular mechanism of AT1R non-desensitization.

RESEARCH ON INTERNATIONAL LEGAL REGIME OF SHIP＇S BALLAST WATER

Harmful alien invasive species transported by ballast water is considered as a significant threat to marine environment. IMO has adopted the International Convention for the Control and Management of Ships＇ Ballast Water and Sediments in 2004 which has not yet come into force. The convention is important for the control and management of ballast water and sediments. Before its entry into force, state responsibilities required under other conventions will help reduce the risk resulting from the spread of harmful alien invasive species carried by ballast water. This paper will discuss the threats of ships＂ ballast water on marine ecological safety at first, and then analyze the nature of harmful alien invasive species, the state＇s prevention obligation will be expounded thereafter, and finally conclude the contents, challenges and defects of the International Convention for the Control and Management of Ships＇ Ballast Water and Sediments of 2004.

Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

Gastric cancer is highly prevalent among digestive tract tumors.Due to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastric cancer.However,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric cancer.In our previous study,we identified a novel small molecule EP4 receptor antagonist called YY001.Treatment with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse model.Furthermore,adminis-tration of YYo01 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 macro-phages.Additionally,our research revealed that YYo01 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than fluorouracil.These findings suggest that YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.