ABSTRACT
Accumulating evidence demonstrates that the nucleus tractus solitarii (NTS) neurons serve as central respiratory chemoreceptors, but the underlying molecular mechanisms remain undefined. The present study investigated the expression of acid-sensitive ether-à-go-go-gene-like (Elk, Kv12) channels in the NTS of mice. Immunofluorescence staining was used to observe the distribution and cellular localization of the Kv12 channels in NTS neurons. Western blot and quantitative real-time PCR (qPCR) were used to evaluate protein and mRNA expression levels of Kv12 channels. The results showed that all of the three members (Kv12.1, Kv12.2, Kv12.3) of the Kv12 channel family were expressed in NTS neurons, and their expressions were co-localized with paired-like homeobox 2b gene (Phox2b) expression. The expression of Kv12.1 mRNA was the largest, whereas the expression of Kv12.3 was the least in the NTS. The results suggest Kv12 channels are expressed in Phox2b-expressing neurons in the NTS of mice, which provides molecular evidence for pH sensitivity in Phox2b-expressing NTS neurons.
Subject(s)
Animals , Mice , Neurons , Potassium Channels, Voltage-Gated , Solitary Nucleus , Transcription Factors/geneticsABSTRACT
Objective At present, the clinical significance and biological function of Msi1 (Musashi1) in colon cancer are still not very clear. So, a comprehensive understanding of the expression and role of Msi1 in colon cancer has important clinical and theoretical significance. This study is to investigate the clinical significance of Msi1 gene and its biological role in colon cancer by lentiviral vector to interfere with Msi1 gene expression in colon cancer SW480 cells. Methods 20 colon cancer specimens were collected from the Second Surgery Department of the Fourth Hospital of Hebei Medical University from October 2013 to May 2014. Each specimen was collected from the cancer tissue and the adjacent intestinal wall tissue. Western blot was performed to determine the protein expression of Msi1 in tumor tissues and adjacent normal tissues from colon cancer patients. The relationship between Msi1 protein expression and clinical characteristics was further analyzed. The lentiviral vector was used to construct a stable SW480 cell line with low expression of Msi1. The lentivirus containing two different interference sequences (shmsi1-1 and shmsi1-2) was transfected into the target cells, and the colon cancer cells were divided into control group (without any treatment), shMsi1-1 group (transfected shMsi1-1) and shMsi1-2 group (transfected shMsi1-2). The two lentivirus silencing effects were detected by Western blot. Cell proliferation was detected by CCK-8 assay, Clone formation assay was conducted to detect the colony forming ability, and Flow cytometry analysis was used to examine the apoptosis rate. Results The protein expression of Msi1 in colon cancer tissue(0.863±0.208) was significantly higher than that in adjacent normal tissues(0.272±0.078), and the difference was statistically significant(P<0.001). The relative expression of Msi1 protein in shMsi1-1 and shMsi1-2 groups (0.299±0.111 and 0.207±0.087) was significantly lower than that in the control group (1.000±0.149) (P<0.001). The proliferation rate of shMsi1-1 and shMsi1-2 at 48 h and 72 h was significantly lower than that of the control group (P<0.01). Compared with the control group (296.33±64.04), shMsi1-1 group (92.00±43.31) and shMsi1-2 group (78.67±32.87) were significantly decreased (P<0.01). Compared with the control group [(4.01±0.26) %], the apoptosis rate of shMsi1-1 group, shMsi1-2 group [(10.22±1.04) %, (10.87±1.27) %] was significantly increased (P<0.001). Conclusion Interference with Msi1 gene expression inhibits proliferation of colon cancer SW480 cells and promotes tumor cell apoptosis. This finding provides a new intervention target for the clinical treatment of colon cancer.
ABSTRACT
Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.
Subject(s)
Animals , Male , Baroreflex , Physiology , Blood Pressure , Hypertension , Metabolism , Hypoxia , Kidney , Metabolism , Nitric Oxide Synthase Type I , Metabolism , Rats, Sprague-Dawley , Solitary Nucleus , MetabolismABSTRACT
Activation of peripheral respiratory chemoreceptors provokes respiratory and cardiovascular reflexes, providing a novel understanding of pathogenic mechanism of hypertension. Here we hypothesize that activation of peripheral respiratory chemoreceptors by hypoxia causes enhanced cardiorespiratory activity in conscious spontaneously hypertensive rats (SHRs). Using whole body plethysmography in combination with radio telemetry, pulmonary ventilation, arterial blood pressure and heart rate were examined in SHRs and Wistar-Kyoto (WKY) rats. We found that exposure to hypoxia induced greater increases in tidal volume and minute ventilation volume in SHRs compared to WKY rats. In addition, hypoxia caused a robust increase in arterial blood pressure and heart rate in SHRs relative to WKY counterparts. After carotid body denervation, the hypoxic ventilatory response was significantly decreased in both SHRs and WKY rats, but without significant difference between the two strains; moreover, the differences of arterial blood pressure and heart rate changes during hypoxic exposure were statistically insignificant between SHRs and WKY rats. It is concluded that hypoxia remarkably potentiates cardiorespiratory activity in the SHRs, suggesting an enhanced sensitivity of carotid bodies to hypoxia.
Subject(s)
Animals , Rats , Blood Pressure , Heart Rate , Hypertension , Hypoxia , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
AIM: To discuss the clinical applications of methods to localize nasal cut ends and the effects of Z-plasty in the surgeries for lower eyelid longitudinal laceration combined with lower lacrimal canaliculi disruption. METHODS: From September, 2010 to October, 2013, a total of 37 patients ( 37 eyes ) with lower eyelid longitudinal laceration combined with lower lacrimal canaliculi disruption were operated for anastomosis of lacrimal canaliculi disruption and suture of lower eyelid longitudinal. Different methods to search for the nasal cut ends of lacerated lacrimal canaliculi, such as “under a microscope directly”, “guided by probing needle” and“pigtail curved probe”. Then, to repair lower eyelid longitudinal laceration with Z-plasty transposition flaps. Follow up was 3mo~2a after operation. RESULTS: All nasal cut ends could be found successfully on 37 patients;Lacrimal duct unobstructed in 31 patients (83. 8%), improved in 5 patients (13. 5%), invalid in 1 patient (2. 7%),the overall successful rate was 97. 3%; the eyelids repair was satisfactory, small scars, the appearance and function was normal. CONCLUSION: The nasal cut ends can be found successfully by “directly under a microscope”, “guided by probing needle” and“pigtail curved probe”;the effect of silicone drainage tube used as lacrimal canaliculi bracket is satisfactory; most patients gained excellent recovery for both appearance and function after Z-plasty.
ABSTRACT
AIM: To evaluate the safety, efficacy and stability of posterior chamber phakic intraocular lens ( ICL ) implanation and clear lens extraction for the correction of high myopia. METHODS: The study enrolled 56 cases ( 100 eyes ) of high myopia. Group I comprised 32 cases ( 58 eyes ) receiving ICL implantation and Group II comprised 24 cases (42 eyes) undergoing clear lens extraction. In this study, we evaluated the two groups of subject's the visual and refractive results, intraocular pressure ( IOP ) , endothelial cell density ( ECD ) , anterior chamber depth ( ACD) , lens transparency, the surgical complications as well as visual adverse symptoms before and after surgery. RESULTS: The postoperative subjects in group I and group II were followed, uncorrected vision acuity ( UCVA)>0. 5 were 69. 0% in group I and 71. 4% in group II after 3mo. UCVA>0. 5 were 72. 4% in group I and 73. 8% in group II after 1a. Predictability of the manifest spherical equivalent refraction within±1. 00D was achieved in 62. 1%of eyes in group I and 57. 1% in group II after 1a. The central vault of the ICL ( distance from posterior surface of ICL to the crystalline lens ) measured with anterior segment optical coherence tomography ( AS-OCT ) was 0. 35-0. 54 (0. 40±0. 16) mm. Twelve point one percent of eyes in group I and 7. 1% of eyes in group II had transient mild increase in IOP. Here were statistically significant differences between preoperative and postoperative ECD (PCONCLUSION: ICL implantation and clear lens extraction are effective, safe and predictable surgical option for the management of high myopia. No severe complications occurred, but its long time effect and safety still need more time to prove.