Monensin inhibits proliferation,migration, and promotes apoptosis of breast cancer cells via downregulating UBA2

Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast gland, the morbidity, and mortality of which continue to increase. Therefore, it is crucial to find new drugs to treat breast cancer. Monensin is a carrier antibiotic that has been reported to inhibit the growth of cancer cells; however, its impacts on breast cancer cells have not been reported. In this article, the cell survival rate was measured by CCK-8. Colony formation assay was utilized to detect the level of cell proliferation. Transwell was used to measure the ability of cell invasion, and wound healing was used to measure the ability of cell migration. RT-qPCR and western blot were, respectively, used to detect the expression of related genes and proteins. The level of apoptosis was detected by flow cytometry. Cell transfection technique was used for overexpressing UBA2. We found that Monensin inhibited the proliferation and migration of breast cancer cells and inhibited the expression of MMP-2 and MMP-9. In addition, Monensin promoted the apoptosis accompanied by the increase of Bax, caspase3, caspase7, and caspase9 and the decreased of bcl-2 of breast cancer cells. Monensin was also found to inhibit UBA2 expression in breast cancer cells. Subsequently, after overexpression of UBA2, the impacts of Monensin on proliferation, migration, and apoptosis of breast cancer cells was inhibited. In conclusion, Monensin can inhibit the proliferation and migration and activate apoptosis of breast cancer cells via downregulating the expression of UBA2.     

Hyperbaric oxygen treatment mitigates liver damage in mice with noise exposure

Noise exposure relates to various pathological disorders including liver damage, preventive measures of which are being demanded. Hyperbaric oxygen treatment (HBOT), as a non-invasive procedure, exerts convincing therapeutic potency on multiple liver diseases. The efficacy of HBOT in mitigating noise induced liver damage (NILD) and associated mechanisms would be elucidated here. Mice were subject to broad band noise (20–20k Hz, 90–110 dB) for 5 days by 3 hours/day. HBOT with 2.5 atmosphere absolute (ata) was employed before noise exposure. Morphology of liver tissue was examined by hematoxylin-eosin (HE) staining. Oil Red O (ORO), transferase-mediated dUTP nick end labelling (TUNEL) test and western blot were utilized to detect lipid accumulation, apoptotic cells and protein expression, respectively. Ceramide (Cer) level was assayed by immunohistochemistry (IHC) analysis. With noise exposure, conspicuous structural derangement and lipid deposition occurred in liver tissue of mice, which was alleviated significantly by the application of HBOT. Meanwhile, HBOT reduced the proportion of apoptotic hepatocytes, restraining the superoxide production in noise exposed mice. In view of underlying mechanisms, noise enhanced the acid sphingomyelinase (ASM) protein expression and the Cer generation in liver tissue of mice which was reversed substantially by HBOT. Altogether, HBOT ameliorates the structural and functional derangement of liver by neutralizing the ASM/Cer pathway in noise exposed mice.     

无创产前检测技术筛查胎儿性染色体非整倍体的临床价值

目的探讨无创产前检测(NIPT)在胎儿性染色体非整倍体(SCA)筛查中的临床价值。方法选择2018年4月至2019年9月,在徐州市妇幼保健院进行NIPT筛查的7144例单胎妊娠孕妇为研究对象。采集孕妇外周血5 mL进行全基因组大规模平行测序,预测发生胎儿SCA的风险值。再对NIPT提示胎儿SCA孕妇,进一步进行羊水穿刺术产前诊断。本研究遵循的程序符合徐州市妇幼保健院伦理委员会所制定的伦理学标准,并得到批准[审批文号:〔2019〕伦审第(05号)]。本研究与受试对象均签署知情同意书。结果①7144例孕妇中,NIPT提示胎儿SCA为27例(0.4%,27/7144)。胎儿SCA的27例胎儿中,13例(48.1%,13/27)胎儿染色体核型为45,X;6例(22.2%,6/27)为47,XXX;5例(18.5%,5/27)为47,XYY;3例(11.1%,3/27)为47,XXY。②对NIPT提示胎儿SCA的27例孕妇中,21例进一步进行羊水穿刺术胎儿染色体核型分析发现,12例无异常,其余9例的结果与NIPT结果相符,SCA阳性预测值为42.8%(9/21)。胎儿染色体核型异常的9例胎儿中,3例胎儿染色体核型为47,XXX;3例为47,XYY;2例为47,XXY;1例为45,X。③由于NIPT结果异常进一步进行羊水穿刺术结果亦异常的9例胎儿45,X,47,XXX,47,XXY和47,XYY阳性预测值分别为10.0%(1/10),75.0%(3/4),67.0%(2/3)和75.0%(3/4),假阳性率分别为90.0%(9/10),25.0%(1/4),33.0%(1/3)和25.0%(1/4)。④NIPT结果显示胎儿染色体核型为47,XNN者进一步行羊水穿刺术后提示真阳性者父母中位年龄均为37岁,高于假阳性者父母(30岁)。结论NIPT在筛查胎儿SCA方面具有较好的应用价值,但是假阳性率较高,仍需进一步进行产前诊断以确诊。     

Iron-Oxide Nanocluster Labeling of Clostridium novyi-NT Spores for MR Imaging–Monitored Locoregional Delivery to Liver Tumors in Rat and Rabbit Models

PurposeTo label Clostridium novyi-NT spores (C. novyi-NT) with iron oxide nanoclusters and track distribution of bacteria during magnetic resonance (MR) imaging-monitored locoregional delivery to liver tumors using intratumoral injection or intra-arterial transcatheter infusion.Materials and MethodsVegetative state C. novyi-NT were labeled with iron oxide particles followed by induction of sporulation. Labeling was confirmed with fluorescence microscopy and transmission electron microscopy (TEM). T2 and T2* relaxation times for magnetic clusters and magnetic microspheres were determined using 7T and 1.5T MR imaging scanners. In vitro assays compared labeled bacteria viability and oncolytic potential to unlabeled controls. Labeled spores were either directly injected into N1-S1 rodent liver tumors (n = 24) or selectively infused via the hepatic artery in rabbits with VX2 liver tumors (n = 3). Hematoxylin-eosin, Prussian blue, and gram staining were performed. Statistical comparison methods included paired t-test and ANOVA.ResultsBoth fluorescence microscopy and TEM studies confirmed presence of iron oxide labels within the bacterial spores. Phantom studies demonstrated that the synthesized nanoclusters produce R2 relaxivities comparable to clinical agents. Labeling had no significant impact on overall growth or oncolytic properties (P >.05). Tumor signal-to-noise ratio (SNR) decreased significantly following intratumoral injection and intra-arterial infusion of labeled spores (P <.05). Prussian blue and gram staining confirmed spore delivery.ConclusionsC. novyi-NT spores can be internally labeled with iron oxide nanoparticles to visualize distribution with MR imaging during locoregional bacteriolytic therapy involving direct injection or intra-arterial transcatheter infusion.     

The acute toxic effects of silver nanoparticles on myocardial transmembrane potential,INa and IK1 channels and heart rhythm in mice

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10^?9–10^?6?g/ml) concentration-dependently depolarized the resting potential, diminished the action potential, and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes, AgNPs (10^?9–10^?7?g/ml) concentration-dependently decreased the Na⁺ currents (I_Na), accelerated the activation, and delayed the inactivation and recovery of Na⁺ channels from inactivation within 5?min. AgNPs at 10^?8?g/ml also rapidly decreased the inwardly rectifying K⁺ currents (I_K1) and delayed the activation of I_K1 channels. Intravenous injection of AgNPs at 3?mg/kg only decreased the heart rate, while at ≥4?mg/kg sequentially induced sinus bradycardia, complete atrio-ventricular conduction block, and cardiac asystole. AgNPs at 10^?10–10^?6?g/ml did not increase reactive oxygen species (ROS) generation and only at 10^?6?g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5?min. Endocytosis of AgNPs by cardiomyocytes was not observed within 5?min, but was observed 1?h after exposing to AgNPs. Comparative Ag⁺ (≤0.02% of the AgNPs) could not induce above toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on ion channels at the nano-scale level, but not caused by Ag⁺, ROS, and membrane injury. These findings provide warning to the nanomedical practice using AgNPs.     

睡眠呼吸暂停患者颈动脉超声多普勒参数分析

目的：为了研究睡眠呼吸暂停综合征（ＳＡＳ）患者的颈动脉Ｄｏｐｐｌｅｒ超声表现并探讨血流参数的变化。方法：用彩色多普勒超声仪，７．０ＭＨｚ探头，选择４０例ＳＡＳ患者作双侧颈动脉Ｄｏｐｐｌｅｒ超声检查，并与４０例无ＳＡＳ、性别、年龄、基础疾病相匹配的对照组比较。结果：①粥样斑块的发生率ＳＡＳ组为４２．５％，对照组为３２．５％（Ｐ＜０．０５）。②阻力指数（ＲＩ）测定ＳＡＳ组明显高于非ＳＡＳ组（Ｐ＜０．０１）。③颈内动脉流速与颈总动脉流速比值（ＶＩＣＡ／ＶＣＣＡ）两组间有非常显著差异（Ｐ＜０．０１）。④ＳＡＳ组颈动脉频谱形态多有改变，文中列出四种波形。结论：作者认为，ＳＡＳ患者颈动脉硬化多较显著，血液动力学改变以外周阻力增加为主。     

High-Frequency Transcranial Magnetic Stimulation Combined With Functional Magnetic Resonance Imaging Reveals Distinct Activation Patterns Associated With Different Dorsolateral Prefrontal Cortex Stimulation Sites

ObjectivesTranscranial magnetic stimulation (TMS) has been extensively used for the treatment of depression, obsessive-compulsive disorder, and certain neurologic disorders. Despite having promising treatment efficacy, the fundamental neural mechanisms of TMS remain understudied.Materials and MethodsIn this study, 15 healthy adult participants received simultaneous TMS and functional magnetic resonance imaging to map the modulatory effect of TMS when it was applied over three different sites in the dorsolateral prefrontal cortex. Independent component analysis (ICA) was used to identify the networks affected by TMS when applied over the different sites. The standard general linear model (GLM) analysis was used for comparison.ResultsICA showed that TMS affected the stimulation sites as well as remote brain areas, some areas/networks common across all TMS sites, and other areas/networks specific to each TMS site. In particular, TMS site and laterality differences were observed at the left executive control network. In addition, laterality differences also were observed at the dorsal anterior cingulate cortex and dorsolateral/dorsomedial prefrontal cortex. In contrast with the ICA findings, the GLM-based results mainly showed activation of auditory cortices regardless of the TMS sites.ConclusionsOur findings support the notion that TMS could act through a top-down mechanism, indirectly modulating deep subcortical nodes by directly stimulating cortical regions.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03394066.     

磁性括约肌增强器治疗胃食管反流病术后不良反应与处理策略

目的拟探讨国产磁性括约肌增强器（MSA）治疗胃食管反流病（GERD）的不良反应与处理策略。 方法按照上海市胸科医院-胜杰康公司磁性括约肌增强器（SS-MSA）临床试验的入排标准,2018年8月至2021年10月共纳入43例GERD患者接受MSA治疗,在腹腔镜下完成SS-MSA植入手术。术后主要疗效评价指标包括24 h酸暴露总时间、受试者服用PPI药物情况及GERD健康相关生活质量评分（GERD-Q）。记录并发症发生情况。本试验已在中国临床试验注册中心注册（注册号：ChiCTR-ONC-16009512）。 结果43例接受MSA治疗患者中,23例完成1年的随访,24 h酸暴露总时间术前9%（6.2%～13.4%）,术后0.4%（0.1%～2.4%）,差异有统计学意义（P<0.001）;术前GERD-HRQL评分为11（8～14）,术后1年为6（6～11）,较术前显著下降,差异有统计学意义（P＝0.001）。受试者术前全部服用质子泵抑制剂（PPI）药物,术后持续性服用PPI药物患者为5例（21.7%,5/23）、入组患者可正常嗳气、打嗝。术后最常见的并发症为吞咽困难,发生率为86%（37/43）,其中95%（35/37例）为轻中度,均在术后1～3个月缓解。2例患者术后1个月左右出现严重吞咽困难,术中分别植入13、14号MSA,均将装置取出。其余腹泻、腹痛、便秘、恶心等并发症,除1例腹泻患者住院治疗外,其余均对症治疗。术后仍有反酸症状持续者27例,短期缓解者13例,存在症状超过3个月的13例,以轻中度为主。1例因反流严重取出装置。1例因胸痛取出装置。 结论SS-MSA手术后并发症主要为吞咽困难,短期内大多数均能缓解。选择好适当型号的MSA装置,良好的术前宣教、术后饮食指导将保证该术式的成功率。