Molecular imaging in oncology: Current impact and future directions

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging—particularly when combined with liquid biopsy for screening purposes—promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

核因子κB受体活化因子配体和肿瘤坏死因子α经炎性牙周膜干细胞外泌体促进破骨细胞分化

目的　慢性牙周炎表现的病理性骨吸收非常常见，牙周膜干细胞（PDLSCs）的外泌体（Exo）对骨吸收的作用和影响尚不明确，本研究分析了该Exo蛋白组分对破骨细胞分化的影响。方法　分别从正畸前拔牙患者和慢性牙周炎患者的牙周膜组织中提取PDLSCs，通过流式细胞术检测表面标记物；通过差速离心分别提取2种细胞的Exo，即Exo-WT和Exo-CP，并通过Western blot、透射电子显微镜（TEM）、蛋白浓度检测、纳米粒径追踪检测Exo特征；通过蛋白质谱检测2种Exo的蛋白组分；通过酶联免疫吸附（ELISA）验证了差异表达蛋白肿瘤坏死因子α（TNF-α）、核因子κB受体活化因子配体（RANKL）、白细胞介素（IL）-1α、转化生长因子β（TGF-β）、骨形态发生蛋白2（BMP-2）表达水平；将10、100、1 000 μg·mL^-1的Exo-CP或Exo-WT加入RAW264.7培养基中并于5 d时通过实时荧光定量聚合酶链反应（RT-qPCR）、Western blot、抗酒石酸酸性磷酸酶（TRAP）染色检测破骨分化相关指标表达情况；采用SPSS 24.0软件对实验数据进行统计学分析。结果　Exo-CP富集的差异表达蛋白主要与破骨细胞分化的TNF信号通路、核转录因子κB（NF-κB）信号通路相关；ELISA实验证实了Exo-CP中高表达TNF-α、RANKL、IL-1α，低表达TGF-β1、BMP-2（P<0.05）；Exo-CP作用于RAW264.7，显著提高了细胞的破骨分化相关基因及蛋白的表达水平，TRAP染色可见分化的破骨细胞，且呈现浓度依赖性，100、1 000 μg·mL^-1浓度Exo-CP对破骨细胞分化的促进作用显著高于10 μg·mL^-1浓度组（P<0.05）。结论　慢性牙周炎的病理性骨吸收可能由炎性PDLSCs所分泌的Exo通过促进破骨细胞分化引起，Exo中主要的作用蛋白可能为RANKL和TNF-α，本研究为慢性牙周炎骨吸收的发病机制提供了新视角。     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Cardiac tamponade in multiple myeloma – A pictorial case review of FDG PET/CT findings

Pericardial involvement of multiple myeloma is a rare and late‐stage complication, with only a few cases reported in the literature. PET/CT has demonstrated a growing role in the diagnosis and follow‐up of patients with multiple myeloma. We present a case of pericardial multiple myeloma in a patient with relapsed/refractory disease, showcasing previously unpublished FDG PET/CT findings.     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.     

天麻素生物合成的研究进展

天麻素是我国名贵中药材天麻中的一种主要活性成分，具有降血压、抗癫痫、抑制肿瘤、保护神经等多方面的药理活性。随着市场对天麻素需求的不断增长以及传统获取方法固有的问题，导致急需新的方法来解决天麻素生产实际中面临的各项困难。生物合成法是一种有别于传统获取法的新方法，已在天麻素获取上取得了较大进展和成果，故现阶段有必要从天麻素生物合成途径、植物转化法和微生物转化法3个方面，对天麻素生物合成进行系统地阐述，从而为进一步改进和完善天麻素生产方法，以满足人们对其不断增长的需求提供有价值的参考。