Alkaloid is one of the main antineoplastic activities in Chinese Herbal Medicine.There has been big progress on the mechanism of antitumor in natural alkaloids and their derivatives in recent years,especially focusing on the targets of hypoxia inducible factor 1,telomere,and topoisomerase.The new trends of these three targets have been reviewed in this paper.

Objective To explore the effect of dronedaronel on hyperpolarization-activated cyclic-nucleotide-gated(HCN) channel expression by detecting the change of HCN channel mRNA and protein level before and after giving dronedarone in neonatal rat ventricular myocytes.Methods Neonatal rat ventricular myocytes were separated and digested by type Ⅱ collagenase,and then single ventricular myocytes were collected through differential sticking wall separation method.According to the concentrations (0.1,0.5,1.0,5.0,10.0,20.0 μmol/L of dronedaronel for treating myocytes for 48 h) and time(10 μmol/L of dronedaronel for treating myocytes for 1,6,12,24,48 h)the gradient grouping was conducted.The levels of HCN2 and HCN4 channel mRNA and protein level were determined by real-time PCR and Western blot.Results The HCN2 mRNA and HCN4 mRNA expression levels in concentration gradient group and time gradient group were lower than those in the control group(P＜0.05);compared with the control group,the protein level in the 10 umol/L dronedaronel treatment for 12 h group was significantly down-regulated(P＜ 0.01).Conclusion Dronedaronel could inhibit the expression of HCN2/HCN4 channel mRNA and protein,moreover its action shows the concentration dependency and reaches the maximum at 12 h after medication.

Objective To investigate the diagnostic value of ultrasound and MRI in fetal bronchopulmonary sequestration (BPS). Methods The 7 pregnant women with suspected fetal BPS were examined with a 1.5 T MR unit within 24 h after prenatal ultrasound in Hubei Maternal and Children's Hospital during July 2013 to February 2015. The imaging protocol included half-fourier acquisition single shot turbo SE (HASTE), true fast imaging with steady state precession (True FISP) in axial, frontal and sagittal planes relative to the fetal thorax. Prenatal MRI findings have been compared with postnatal enhanced computed tomography or biopsy. Results The locations of BPS were in left side in 5 cases and in right side in 2 cases. One case was complicated with congenital cystic adenomatoid malformation (CCAM) of lung. Ultrasound showed the intrathoracic mass as a hyperechoic lesion and the feeding artery could be found by Doppler ultrasonography. T2WI could reveal not only the hyperintense lesions with clear boundary, but also the hypointense feeding artery originating from systemic circulation. Compared with pathological examination or enhanced CT, both of the ultrasound and the MRI could locate the lesions;however 2 feeding arteries were misjudged. Conclusions Prenatal ultrasound is the first-choice diagnostic modality for BPS. MRI can demonstrate the location, morphology and the feeding arteries of the fetal BPS, and also estimate the volume of normal lungs, which could be an important supplement to prenatal ultrasound in prenatal diagnosis and prognostic prediction of BPS.

Objective: To evaluate left ventricular (LV) dysfunction in patients with esophageal cancer (EC) during concurrent chemoradiotherapy (CCRT) using real-time three-dimensional speckle tracking echocardiography (3D-STE) and analyze its influence factors. Methods: Thirty-one patients with EC who received CCRT were enrolled in the study.Conventional echocardiography and 3D-STE were performed pre-CCRT and during CCRT (radiotherapy dose reached 40Gy). Three-dimensional parameters including LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) as well as global circumferential strain (GCS) were compared between pre-CCRT and during CCRT. The independent factors on left ventricular function parameters were analyzed. Results: There was no change on LV diameters, LV volumes and LVEF during CCRT (all P>0.05), while LV diastolic function indexes were impaired compared with those of pre-CCRT, demonstrated by the decreased E/A, Em/Am, and increased E/Em(all P<0.05). 3DGLS was also significantly decreased during CCRT compared with that of pre-CCRT (P<0.05), but no significant difference was found in 3DGCS (P>0.05). Multivariate linear regression analysis manifested that cardiac V40(the percentage of cardiac volume as radiotherapy dose reached 40Gy) was an independent determinant of LV 3DGLS in patients with esophageal cancer during CCRT (P<0.05). Conclusions LV GLS provided by real-time 3D-STE could sensitively detect CCRT-induced myocardial injury. Cardiac V40 is independently associated with LV 3DGLS during CCRT, representing the impact of radiotherapy on the subclinical LV function change.

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*