Mechanism of Zhishi Xiebai Guizhitang in Treating AS Based on Regulation of Cholesterol Metabolism in Foam Cells by TRPA1 / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg-1） and simvastatin group （0.002 g·kg-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury / 中国药理学通报

Aim To investigate the role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury and related mechanism. Methods SD rats were randomly divided into five groups: Sham operation group(Sham), model group(IR), remote preconditioning of trauma group(RPCT), TRPA1 inhibitor+remote preconditioning of trauma group(TCS+RPCT)and TRPA1 inhibitor group(TCS). The model of myocardial ischemia/reperfusion in rats was established, and the hemodynamics was monitored throughout the process. After reperfusion, the rat heart was taken to measure the myocardial infarction area and myocardial apoptosis rate, the activity and protein expression of mitochondrial aldehyde dehydrogenase 2(ALDH2)and the expression of 4-hydroxynonenal(4-HNE)were detected. Results Compared with sham group, myocardial infarction area and myocardial apoptosis cell increased. Meanwhile, the activity and expression of ALDH2 decreased and the production of 4-HNE increased in IR group. However, compared with IR group, RPCT group had decreased myocardial infarction area and the rate of cardiomyocyte apoptosis, the activity and expression of ALDH2 increased, the production of 4-HNE decreased. And then, compared with RPCT group, TCS+RPCT group reduced the myocardial protective effect of remote preconditioning of trauma. Conclusions TRPA1 receptor mediates the effect of remote preconditioning of trauma alleviating myocardial ischemia/reperfusion injury in rats. Its mechanism may be related to regulating ALDH2 activity and protein expression, and affecting the content of 4-HNE.

Taquicardia ventricular asociada a mutación en el gen de ankirina B / Ventricular tachycardia associated to a mutation in the ankyrin B gen

Resumen Se presenta el caso de una mujer de 14 años, con taquicardiomiopatía secundaria a taquicardia ventricular. Se evidenció la presencia de una variante de significado incierto en el gen ANK2, por lo que se consideró un posible síndrome de ankirina B. La paciente fue tratada con éxito a través de ablación con radiofrecuencia. Tras dicho procedimiento, tuvo recuperación completa de su función ventricular izquierda y resolución de los complejos ventriculares prematuros y los episodios de taquicardia ventricular.

Abstract We report a case of a 14-year-old with tachycardiomyopathy due to ventricular tachycardia. A variant of uncertain significance of the ANK2 gene was identified, which is suggestive of a possible ankyrin-B syndrome. The patient underwent a successful radiofrequency ablation. After the procedure, the patient completely recovered her left ventricular function and there was resolution of the premature ventricular complexes and ventricular tachycardia.

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Effect of Houpu Mahuangtang on Airway Inflammation and Expression of TRPA1, TRPV1 mRNA and Protein in Asthmatic Mice / 中国实验方剂学杂志

<b>Objective::To investigate the effect of Houpu Mahuangtang on airway inflammation and expressions of gene and proteins of Transient receptor potential ankyrin 1, vanilloid 1 (TRPA1, TRPV1) in asthmatic mice. <b>Method::Sixty female Balb/c mice were randomly divided into six groups: control group, model group, low, medium and high-dose Houpu Mahuangtang groups (7, 14, 28 g·kg^-1) and dexamethasone group (0.002 4 g·kg^-1), with 10 mice in each group. A mouse model of asthma was replicated by sensitizing and challenging with ovalbumin. The changes of enhanced pause (Penh) following acetylcholine chloride (ACh) inhalation were detected. The pathological changes of the lung tissues were observed. The number of eosinophils (EOS) in peripheral blood and the percentage of EOS in bronchoalveolar lavage fluid (BALF) were detected. Interleukin (IL)-4, IL-13, prostaglandin D₂ (PGD₂) and substance P (SP) were detected by enzyme-linked immuno sorbent assay (ELISA). The expressions of TRPA1 and TRPV1 gene and protein in lung tissues were detected by Quantitative Real-time polymerase chain reaction (Real-time PCR) and Western blot. <b>Result::Compared with control group, mice of model group showed significantly increased in Penh following ACh inhalation (<italic>P</italic><0.05, <italic>P</italic><0.01), EOS in blood and the percentage of EOS in BALF (<italic>P</italic><0.01). Histopathological changes in lungs showed inflammatory cell infiltration and bronchial mucosa damage. The levels of IL-4, IL-13, PGD₂ and SP in BALF and the expressions of TRPA1, TRPV1 mRNA and protein in lung tissues significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with model group, treatment groups had significant effects in decreasing Penh, relieving lung injury, reducing EOS count in blood and the percentage of EOS in BALF (<italic>P</italic><0.05, <italic>P</italic><0.01), reducing IL-4, IL-13, PGD₂ and SP levels in BALF (<italic>P</italic><0.05, <italic>P</italic><0.01), as well as down-regulating TRPA1 and TRPV1 mRNA and protein expressions in lung tissues (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::Houpu Mahuangtang could reduce airway inflammation, airway responsiveness. In addition to the reduction of levels of Th2 related cytokines, the mechanism of Houpu Mahuangtang might be related to the regulation of TRPA1, TRPV1 mRNA and protein expressions, and the decrease of associated neurofactor levels.

Study on expression of the guanylate binding protein 5 and ArfGAP with SH3 domain ankyrin repeat and PH domain 1 genes among pulmonary tuberculosis patients and populations with latent tuberculosis infection / 中国医师进修杂志

Objective To investigate the expression of guanylate binding protein 5 (GBP5) and ArfGAP with SH3 domain ankyrin repeat and PH domain 1 (ASAP1) genes in pulmonary tuberculosis patients and tuberculosis latent population. Methods Forty pulmonary tuberculosis patients (pulmonary tuberculosis group), 40 latent tuberculosis infection patients (latent tuberculosis infection group) and 40 cases of healthy control (healthy control group) were selected from August 2016 to May 2017. The gene expression was detected in 4 ml peripheral anticoagulant blood by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the relative expression of two genes in three groups were compared. Results The GBP5 gene expression in three groups was significantly differentce (F=7.23, P=0.001). The GBP5 gene relative expression in pulmonary tuberculosis group was significantly higher than that in latent infection group :1.58 ± 0.80 vs. 1.09 ± 0.68, there was significant difference (t=2.93, P=0.004). The GBP5 gene relative expression in pulmonary tuberculosis group was significantly higher than that in healthy control group: 1.58 ± 0.80 vs. 1.04 ± 0.61, there was significant difference (t=3.40, P=0.010). The GBP5 gene relative expression in latent infection group and healthy control group had no significant difference (t=0.39, P=0.700). There was no significant difference in ASAP1 expression among three groups (F=0.26, P=0.770). Conclusions The expression of GBP5 in pulmonary tuberculosis patients, latent tuberculosis infection patients and healthy controls is different, and GBP5 could screen latent tuberculosis infection patients which is expected to be a potential screening marker for latent tuberculosis infection.

Relationship between metabotropic glutamate receptor 5 and N-methyl-D-aspartate receptor and their roles in diseases / 上海交通大学学报（医学版）

Metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor (NMDAR) belongs to metabotropic and ionotropic glutamate receptor family, respectively. In recent years, a lot of attention has been paid to these two types of glutamate receptors in the field of neuroscience and psychiatry. This article mainly summarized the research progress of the relationship between these two kinds of receptors and the influence of their relationship on different diseases.

The role of B-cell scaffold protein with ankyrin repeats 1 in collagen-induced arthritis / 中华风湿病学杂志

Objective To analyze the roles of B-cell ccaffold protein with ankyrin repeats 1 (BANK1) in collagen-induced arthritis (CIA) murine model and the correlation with disease severity.Methods CIA murine model were established and evaluated.In different disease stages,the serum levels of anti-C Ⅱ auto-antibodies and BANK1 were detected by electrochemiluminescence immunoassay(ELISA).Moreover,the expression of BANK1 mRNA in peripheral blood cells were detected by real-time polymerase chain reaction (PCR) and its correlation with clinical scores was analyzed.Then the percentage of BANK1 expression in B cells in spleen and draining lymph nodes were detected by flow cytometry and the level of BANK1 protein in spleen was detected by Western blotting according to the results afore mentioned.The data was analyzed by Statistical Product and Service Solutions (SPSS) Stastistics 21.0 and figures were made with Graph Pad Prism 6.Repeated measure ANOVA was used to assess differences between the two groups.Correlations were analyzed by Spearman correlation analysis.Linear regression analysis was done when a correlation was identified.Results The incidence of CIA was over 90％.The clinical scores of arthritic mice was positively correlated with the serum levels of anti C Ⅱ total IgG antibody (r=0.717 5,P ＜0.01),anti C] IgG2a antibody (r=0.675 3,P＜0.01) and anti C Ⅱ IgG2b antibody (r=0.889 4,P＜0.01) respectively.The BANK1 level in the serum and the BANK1 mRNA expression were significantly decreased in different disease stages in CIA mice when compared with normal mice.The negative correlation between the BANK1 mRNA expression and clinical scores (r=-0.485 4,P＜0.01) was observed.The percentage of BANK1 +CD19+ cells in spleen and draining lymph nodes and the level of BANK1 protein in spleen were reduced in CIA as well.Conclusion Along with the disease progress in CIA,BNK1 expression is declined,which weakens the negative regulation of BANK1 on B cells.This change goes hand in hand with the severity of arthritis.

Hereditary polycythemia caused by mutation of ANK1 gene:a case report / 临床儿科杂志

Objective To explore the genetic characteristics, diagnosis, and treatment of hereditary spherical polycythemia (HS). Methods The clinical data of one case of HS was analyzed retrospectively, and related literatures were reviewed. Results The 5-year-old girl presented hemolytic anemia from 6 months old. Incubation of fragility tests was positive. Blood smears and red cell electron microscopy showed spherical red blood cells. DNA sequencing showed alterations in heterozygosity of stopgain SNV. The girl was diagnosed was HS, and was scheduled to undergo splenectomy at 6 years old. Conclusions HS is an autosomal dominant genetic disease, mainly manifested as anemia, hemolytic anemia, and splenomegaly. The early diagnosis depends on genetic testing.

Expressions of TRPV1 and TRPA1 in the dorsal root ganglion in the rat model of orchialgia / 中华男科学杂志

Objective@#To explore the expressions of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in the dorsal root ganglion (DRG) and their action mechanisms in the rat model of orchialgia.@*METHODS@#The models of orchialgia were established in male SD rats by injection of 2% acetic acid into the testis. Then the number of spontaneous pain responses and withdrawal latency in the model rats were recorded by behavioral tests and the expressions of TRPV1 and TRPA1 in T13－L1 DRGs determined by RT-qPCR, Western blot and immunofluorescence staining.@*RESULTS@#Compared with the normal control rats, the orchialgia models showed a significant increase in the number of spontaneous pain responses (0.13 ± 0.35 vs 22.63 ± 3.42, P<0.01) and a decrease in the withdrawal latency at 4 hours after injection (［12.75 ± 1.50］ vs ［4.85 ± 1.00］ s, P<0.05). The mRNA expressions of both TRPV1 and TRPA1 were observed in the membrane of the neurons in the DRG, the former increased by 1.77 times and the latter by 1.75 times that of the control (P<0.05).@*CONCLUSIONS@#The expressions of TRPV1 and TRPA1 were up-regulated in the DRG of the rat models of orchialgia, which may be involved in the allodynia and hyperalgesia of the rats.

Investigaion about the mRNA expression of ASB2 and Jak3 in patients with acute lymphoblastic leuke-mia / 国际肿瘤学杂志

Objective To explore the expression of ankyrin-repeat SOCS box containing protein 2 (ASB2)and Janus kinase 3 (Jak3)mRNA in bone marrow plasma mononuclear cells of patients with acute lymphoblastic leukemia (ALL)and discuss the correlation of them.Methods Bone marrow plasma was collected from 48 patients of newly diagnosed ALL (37 cases B-ALL and 11 cases T-ALL)and 34 non leukemia patients (control group),respectively.Expression levels of ASB2 and Jak3 mRNA were detected by real-time quantitative PCR.Results The expression of ASB2 mRNA in B-ALL and T-ALL were significantly different compared to control group (t =14.2,P <0.01;t =15.2,P <0.01),which were 68.5,32.7 folded more than control group,respectively.Moreover,the expression level of Jak3 mRNA in B-ALL group and T-ALL group were 2 336.1 and 7 131.5 folded more than control group (t =37.3,P <0.01;t =37.6,P <0.01). At last,the expression of ASB2 and Jak3 gene was positive correlation (r =0.523,P <0.001).Conclusion ASB2 and Jak3 are expressed abnormally in ALL patients and the correlation of them is positive.ASB2 and Jak3 may be related to the proliferation and differentiation in leukemia cells.

Cannabinoids increase mechanosensitivity of trigeminal ganglion neurons innervating the inner walls of rat anterior chambers via activation of TRPA1 / 华中科技大学学报（医学）（英德文版）

Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro. Rat TG neurons innervating the inner walls of the anterior chambers were labeled by 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfona (FAST DiI). Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. WIN evoked inward currents via TRPA1 activation in FAST DiI-labeled TG neurons. WIN enhanced mechanosensitive currents via TRPA1 activation in FAST DiI-labeled TG neurons. Our results indicate that cannabinoids can enhance the mechanosensitivity of TG endings in the inner walls of anterior chambers of rat eye via TRPA1 activation.

Transient Receptor Potential Ankyrin 1 Channel in Neuropathic Pain (review) / 中国康复理论与实践

Transient receptor potential ankyrin 1 (TRPA1) is a family member of the transient receptor potential (TRPs). It is primarily localized to a subpopulation of primary sensory neurons, such as trigeminus, vagus and dorsal root ganglia. Neuropathic pain is often caused by peripheral nerve injury, diabetes and chemotherapeutics. A large of oxidative/nitrative stress products are produced during neuropathic pain, which cause acute nociception, allodynia, and hyperalgesia. TRPA1 antagonists may be beneficial in the treatment of neuropathic pain. Here, the role of TRPA1 in neuropathic pain is summarized.

Effects of pelvic nerve transection on the colonic motility and the expression of transit receptor potential ankyrin 1 in a rat model / 中华消化外科杂志

Objective To investigate the effects of pelvic nerve transection on the colonic motility and the expression of transit receptor potential ankyrin 1 (TRPA1) in the colon mucosa.Methods Ninety-six Sprague-Dawley rats were divided into 3 groups based on a random number table:(1) 18 rats in the control group remained untreated and were fed regularly;(2) 39 rats in the sham operation group received laparotomy,and the pelvic nerves were stripped;(3) 39 rats in the operation group received laparotomy with pelvic nerve transection before abdominal closure.Colonic transit was assessed respectively at postoperative day 1,3,and 7 by injecting and calculating the geometric center (GC) of the distribution of 51Cr after 3 hours of propagation.The expression of TRPA1 in the colonic mucosa was determined by Western blot at postoperative day 1,3,7.Data with normal distribution were expressed by (x)± s,and were analyzed using the repeated measures ANOVA or LSD test.Results The GC values of the distribution of 51Cr in the sham operation group at postoperative day 1,3,7 were 5.8 ± 0.9,7.5 ± 0.5,7.3 ± 0.5,with a significant difference (F =9.508,P ＜ 0.05).The GC values of the distribution of 51Cr in the operation group at postoperative day 1,3,7 were 4.9 ± 0.4,5.6 ± 0.4,6.4 ± 0.8,with a significant difference (F =11.689,P ＜ 0.05).There were significant differences in the GC values of the distribution of 51 Cr at postoperative day 1 and 3 between the sham operation group and the operation group (t =2.227,7.144,P ＜ 0.05),while no significant difference was detected at postoperative day 7 (t =2.162,P ＞ 0.05).The results of Western blot showed that the relative expressions of TRPA1 in the proximal part of the colon at postoperative day 1,3,7 were 1.00 ± 0.05,1.00 ± 0.07,1.00 ± 0.06 in the control group,with a significant difference (F =0.055,P ＞ 0.05).The relative expressions of TRPA1 in the proximal part of the colon at postoperative day 1,3,7 were 0.78 ± 0.09,0.94 ± 0.08,0.95 ± 0.12 in the sham operation group,with a significant difference (F =5.651,P ＜ 0.05).The relative expressions of TRPA1 in the proximal part of the colon at postoperative day 1,3,7 were 0.37 ± 0.12,0.89 ± 0.10,0.92 ± 0.14 in the operation group,with a significant difference (F =41.005,P ＜0.05).There was significant difference in the relative expressions of TRPA1 in the proximal part of the colon among the 3 groups at postoperative day 1 (F =73.497,P ＜ 0.05),while significant differences were respectively detected between the control group and the sham operation group and the operation group at postoperative day 1 (t =4.224,11.954,P ＜ 0.05),and significant difference between the operation group and the sham operation group was also observed (t =7.730,P ＜ 0.05).There was no significant difference in the relative expression of TRPA1 in the proximal part of the colon among the 3 groups between day 3 and day 7 (F =2.087,0.656,P ＞ 0.05).The relative expressions of TRPA1 in the distal part of the colon at postoperative day 1,3,7 were 1.00 ± 0.05,1.00 ± 0.07,1.00 ± 0.06 in the control group,with no significant difference (F =0.055,P ＞ 0.05).The relative expressions of TRPA1 in the distal part of the colon at postoperative day 1,3,7were 0.68 ±0.11,0.98 ±0.12,1.11 ±0.16 in the sham operation group,with a significant difference (F =16.975,P ＜ 0.05).The relative expressions of TRPA1 in the distal part of the colon at postoperative day 1,3,7 were 0.39 ± 0.12,0.78 ± 0.10,1.06 ± 0.13 in the operation group,with a significant difference (F =50.417,P ＜ 0.05).There were significant differences in the relative expression of TRPA1 in the distal part of the colon among the 3 groups between day 1 and day 3 (F =58.773,8.680,P ＜ 0.05),while significant differences were respectively detected between the control group and the sham operation group and the operation group at postoperative day 1 (t =5.706,10.837,P ＜ 0.05),and significant difference was also detected between the operation group and the sham operation group (t =5.131,P ＜ 0.05).There was no significant difference in the relative expression of TRPA1 in the distal part of the colon between the control group and the sham operation group at postoperative day 3 (t =0.166,P ＞ 0.05),while significant differences were respectively detected between the control group and the operation group and between the sham operation group and the operation group at postoperative day 3 (t =3.694,3.528,P ＜ 0.05).There was no significant difference in the relative expression of the TRPA1 in the distal part of the colon between the 3 groups at postoperative day 7 (F =1.319,P ＞ 0.05).Conclusions Injury to pelvic nerves adversely affects colonic transit and expression of TRPA1 in mucosa.With a compensatory mechanism from the intestinal itself,these alterations in intestinal motility function normalize over time suggesting expression of TRPA1 in mucosa plays a crucial role in the recovery of intestinal motility function.

Expression of transit receptor potential ankyrin 1 and 5-hydroxytryptamine in the colonic mucosa of patients with slow transit constipation / 中华消化外科杂志

Objective To investigate the expression of transit receptor potential ankyrin 1 (TRPA1) and 5-hydroxytryptamine (5-HT) in the colonic mucosa of patients with slow transit constipation (STC).Methods The clinical data of 10 patients with STC and 10 patients with sigmoid cancer who were respectively admitted to the Daping Hospital of the Third Military Medical University from March 2013 to March 2014 and from December 2013 to May 2014 were retrospectively analyzed.Ten and 10 surgical specimens of descending colon from patients with STC and sigmoid cancer (tumor edge measuring in controls ＞ 10 cm) were allocated into the STC group and the control group,respectively.The expressions of TRPA1 and 5-HT in the colonic mucosa in the control group and in the 2 groups were detected by immunofluorescence and immunochemistry staining,respectively.The expression of TRPA1 in the colonic mucosa was observed by Western blot test.The measurement data with normal distribution was presented as x ± s,and the comparison between groups were analyzed using the t test.Results The results of immunofluorescence showed that TRPA1 and 5-HT were co-expressed in the colonic mucosa of controls.The results of immunochemistry staining showed that the integrated optical density (IOD) of expressions of TRPA1 and 5-HT in the STC group and in the control group were 3 619 ± 1 702,55 721 ±28 613 and 9 894 ± 3 325,12 949 ± 2 200,respectively,showing significant differences between the 2 groups (t =-5.312,4.713,P ＜ 0.05).The results of Western blot test showed that the relative expressions of TRPA1 in the STC group and in the control group were 0.8 ± 0.3 and 1.5 ± 0.5,showing a significant difference between the 2 groups (t =-2.379,P ＜ 0.05).Conclusions TRPA1 is expressed in the enterochromaffin (EC) cells of colonic mucosa.High expression of 5-HT and low expression of TRPA1 in the colonic mucosa are closely related with the pathogenesis of STC.

Multiplex ligation-dependant probe amplification study of children with idiopathic mental retardation in South India.

BACKGROUND: Mental retardation (MR) is a heterogeneous dysfunction of the central nervous system exhibiting complex phenotypes and has an estimated prevalence of 1-3% in the general population. However, in about 50% of the children diagnosed with any form of intellectual disability or developmental delay the cause goes undetected contributing to idiopathic intellectual disability. MATERIALS AND METHODS: A total of 122 children with developmental delay/MR were studied to identify the microscopic and submicroscopic chromosome rearrangements by using the conventional cytogenetics and multiplex ligation dependent probe amplification (MLPA) analysis using SALSA MLPA kits from Microbiology Research Centre Holland [MRC] Holland. RESULTS: All the recruited children were selected for this study, after thorough clinical assessment and metaphases prepared were analyzed by using automated karyotyping system. None was found to have chromosomal abnormality; MLPA analysis was carried out in all subjects and identified in 11 (9%) patients. CONCLUSION: Karyotype analysis in combination with MLPA assays for submicroscopic micro-deletions may be recommended for children with idiopathic MR.

Hesperetin Stimulates Cholecystokinin Secretion in Enteroendocrine STC-1 Cells

Hesperetin (3',5,7-trihydroxy 4'-methoxyflavanone) and its glycoside hesperidin (hesperetin 7-rhamnoglucoside) in oranges have been reported to possess pharmacological effects related to anti-obesity. However, hesperetin and hesperidin have not been studied on suppressive effects on appetite. This study examined that hesperetin and hesperidin can stimulate the release of cholecystokinin (CCK), one of appetite-regulating hormones, from the enteroendocrine STC-1 cells, and then examined the mechanisms involved in the CCK release. Hesperetin significantly and dose-dependently stimulated CCK secretion with an EC50 of 0.050 mM and increased the intracellular Ca2+ concentrations ([Ca2+]i) compared to the untreated control. The stimulatory effect by hesperetin was mediated via the entry of extracellular Ca2+ and the activation of TRP channels including TRPA1. These results suggest that hesperetin can be a candidate biomolecule for the suppression of appetite and eventually for the therapeutics of obesity.

Anti-UACA autoantibody in thyroid-associated ophthalmopathy / 中华内分泌代谢杂志

Serum anti-uveal autoantigen with coiled coil domains and ankyrin repeats (UACA) antibody titer was measured using ELISA in 32 patients with thyroid-associated ophthalmopathy ( TAO ) and 20 patients with Graves' disease (GD) without ophthalmopathy.The level of anti-UACA antibody in TAO group was higher than that in GD group [ (225.91 ± 144.21 vs 187.42 ± 46.77 ) pg/ml,P＜0.05 ],and especially higher in patients with ocular myopathy [ (254.35 ± 168.29 ) pg/ml ].It seems that anti-UACA antibody is the sensitive clinical marker of ocular myopathy in TAO patients.

Murine Cytomegalovirus IE3 Protein Interacts with Ankrd17 / 华中科技大学学报（医学）（英德文版）

Murine cytomegalovirus (MCMV) IE3 protein is a multifunctional viral protein that interacts with several target proteins of both viral and host cellular origin.To investigate the biological function of IE3 in the pathogenesis of the brain disorders caused by CMV,a screening for host cellular proteins that could interact with IE3 was performed.By yeast two-hybrid screening,ankyrin repeats domain 17 (Ankrd17,also known as Gtar) was identified as a host factor that could interact with IE3.This interaction was verified by yeast two-hybrid assay and chemiluminescent co-immunoprecipitaion.Mapping analysis suggested that the 1-148 residues of IE3 were responsible for the interaction.These results suggested that the interaction between Ankrd17 and IE3 may play a key role in the pathogenesis of MCMV-associated disease.

Association study of schizophrenia and ankyrin repeat and kinase domain containing 1 gene polymorphism / 中华行为医学与脑科学杂志

Objective To detect the genetic association between schizophrenia and polymorphism of Ankyrin repeat and kinase domain containing 1 ( ANKK1 ) gene. Methods Observed in a sample of 112 parent/offspring trios where the proband net the American Classification and diagnostic Criteria for Mental Disorders The Forth Revised Edition, criteria for schizophrenia using correlation analysis and haplotype relative risk analysis. The polymorphism of Ankyrin repeat and kinase domain containing 1 gene was detected with PCR methods and SNP typing in all nucleus families. Results The rs2734849 allele was connected with schizophrenia(P= 0. 026). Allele T was protective factor( Z= -2.19) and allele A was the hazard factor( Z=2. 19). The rs4938015,rs7118900 and rs1800497 allele were independence with schizophrenia. Three kinds haplotypes of G/A in the rs7118900 -rs2734849, A/C in the rs2734849 -rs1800497, G/A/C in the rs7118900 -rs2734849 -rs1800497 were associated with schizophrenia ( The P values were 0.032,0. 041,0.046, the genotype frequencies were 0. 36,0.29,0. 17 ).Conclusion It shows an association between schizophrenia and the polymorphism at nucleotide of ankyrin repeat and kinase domain containing 1 gene in Chinese.