The aim of this study was to localize oxytocin receptor (OTR) in the stomach and to investigate the effect of OT on gastric motility in rats. Western blot and immunohistochemistry methods were used to localize OTR in stomach. The motility of stomach was recorded in vivo (recording of the intragastric pressure), in vitro (recording of the contraction of muscle strips) and on isolated smooth muscle cells. OTR was expressed on cells of both circular and longitudinal muscle of stomach. Systemic administration of OT induced an early transient decrease and a subsequent increase on intragastric pressure. Devazepide (1 mg kg(-1), i.v.), a cholecystokinin-1 (CCK(1)) receptor antagonist, completely abolished the transient response but did not influence the subsequent one. OT (10(-9)-10(-6) mol L(-1)) dose-dependently increased the contraction of the muscle strips of gastric body, antrum, and pyloric sphincter, and decreased the average cell length of isolated smooth muscle cells. Tetrodotoxin and atropine did not influence the effect of OT on muscle strips. Pretreatment with atosiban, an OTR antagonist, inhibited the spontaneous contraction of muscle strips and abolished the excitatory effect of OT on the muscle strips and the isolated cells. These results suggest that the OTR is expressed on the smooth muscle of the stomach and mediates excitatory effect of OT on gastric motility.
Stress and its related hormones epinephrine (E) and norepinephrine (NE) play a crucial role in tumor progression. Macrophages in the tumor microenvironment (TME) polarized to M2 is also a vital pathway for tumor deterioration. Here, we explore the underlying role of macrophages in the effect of stress and E promoting breast cancer growth. It was found that the weight and volume of tumor in tumor bearing mice were increased, and dramatically accompanied with the rising E level after chronic stress using social isolation. What is most noteworthy, the number of M2 macrophages inside tumor was up-regulated with it. The effects of E treatment appear to be directly related to the change of M2 phenotype is reproduced in vitro. Moreover, E receptor ADRβ2 involved in E promoting M2 polarization was comprehended simultaneously. Our results imply psychological stress is influential on specific immune system, more essential for the comprehensive treatment against tumors. [BMB Reports 2015; 48(5): 295-300]
PTEN has been studied in several tumor models as a tumor suppressor. In this study, we explored the role of PTEN in the inhibition state of polarized M2 subtype of macrophage in tumor microenvironment (TME) and the underlying mechanisms. To elucidate the potential effect in TME, RAW 264.7 macrophages and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. After PTEN was down-regulated with shRNA, the expression of CCL2 and VEGF-A, which are definited to promote the formation of M2 macrophages, have a dramatically increase on the level of both gene and protein in co-cultured RAW 264.7 macrophages. And at the same time, NHERF-1 (Na C /H C exchanger regulating factor-1), another tumor suppressor has a similar tendency to PTEN. Q-PCR and WB results suggested that PTEN and NHERF-1 were consistent with one another no matter at mRNA or protein level when exposed to the same stimulus. Coimmunoprecipitation and immunofluorescence techniques confirmed that PTEN and NHERF-1 were coprecipitated, and NHERF-1 protein expression was properly reduced with rCCL2 effect. In addition, cell immunofluorescence images revealed a profound transferance, in co-cultured RAW 264.7 macrophages, an up-regulation of NHERF-1 could promote the PTEN marked expression on the cell membrane, and this form for the interaction was not negligible. These observations illustrate PTEN with a certain synergy of NHERF-1, as well as down-regulation of CCL2 suppressing M2 macrophage transformation pathway. The results suggest that the activation of PTEN and NHERF-1 may impede the evolution of macrophages beyond the M1 into M2 phenotype in tumor microenvironment.
Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15–24 years and 25–34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803–0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989–0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment.
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