Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression

Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.     

朝鲜淫羊藿酸性多糖的理化特性及对HepG2细胞脂质堆积的改善作用＊

目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性，并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖（EFPA）的均一性和分子量，高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖（EFPA-R）的单糖组成；采用油酸（OA）处理HepG2细胞诱导建立脂质蓄积模型，不同浓度EFPA与EFPA-R（10、30、100、300 μg·mL^-1）分别和OA共同作用于细胞24 h，采用CCK-8试剂盒测定细胞存活率，油红O染色观察细胞内脂滴蓄积情况，并采用试剂盒测定细胞内总胆固醇（TC）、甘油三酯（TG）含量。结果 EFPA为成分均一的多糖组分，分子量为125.8 kDa，由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成，摩尔比为1.7∶7.4∶1.4∶1.8∶1.0，葡萄糖占比最大，EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成，摩尔比为0.8∶10.6∶2.1∶1.0；在10-300 μg·mL^-1范围内，EFPA和EFPA-R对HepG2细胞的抑制作用较弱，作为给药浓度；与空白组相比，模型组细胞中TC、TG含量显著升高（P < 0.01），细胞内红色脂滴显著增多，与模型组相比，EFPA可显著降低细胞中TC、TG含量（P < 0.01），明显减少细胞内红色脂滴（P < 0.05或P < 0.01），EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况，且呈现剂量依赖性，而半乳糖醛酸（GalA）的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。     

The Cystine Knot Is Responsible for the Exceptional Stability of the Insecticidal Spider Toxin ω-Hexatoxin-Hv1a

The inhibitor cystine knot (ICK) is an unusual three-disulfide architecture in which one of the disulfide bonds bisects a loop formed by the two other disulfide bridges and the intervening sections of the protein backbone. Peptides containing an ICK motif are frequently considered to have high levels of thermal, chemical and enzymatic stability due to cross-bracing provided by the disulfide bonds. Experimental studies supporting this contention are rare, in particular for spider-venom toxins, which represent the largest diversity of ICK peptides. We used ω-hexatoxin-Hv1a (Hv1a), an insecticidal toxin from the deadly Australian funnel-web spider, as a model system to examine the contribution of the cystine knot to the stability of ICK peptides. We show that Hv1a is highly stable when subjected to temperatures up to 75 °C, pH values as low as 1, and various organic solvents. Moreover, Hv1a was highly resistant to digestion by proteinase K and when incubated in insect hemolymph and human plasma. We demonstrate that the ICK motif is essential for the remarkable stability of Hv1a, with the peptide’s stability being dramatically reduced when the disulfide bonds are eliminated. Thus, this study demonstrates that the ICK motif significantly enhances the chemical and thermal stability of spider-venom peptides and provides them with a high level of protease resistance. This study also provides guidance to the conditions under which Hv1a could be stored and deployed as a bioinsecticide.     

The influence of physicochemical properties on the reactivity and stability of acyl glucuronides†

1.?Formation of 1-O-acyl-β-d-glucuronide conjugates is a significant pathway in the metabolism of drugs containing a carboxylic acid group. The formation of acyl glucuronides results in an increase in both the aqueous solubility and molecular mass of the conjugate in comparison to the parent drug and thus facilitates excretion in both urine and bile.

2.?Acyl glucuronides are effectively esters, which undergo first order decomposition by both hydrolysis and the intra-migration of the acyl group around the glucuronide ring to yield 2-, 3- and 4-O-glucuronic acid esters which, unlike the metabolically formed 1-O-acyl-β-d-glucuronides, are not substrates for β-glucuronidase. The first order degradation half-life is therefore a composite value of these two reactions and a useful indicator of chemical reactivity and potential toxicity.

3.?Intra-molecular migration is expected to be the predominant pathway due to entropic considerations.

4.?Such conjugates, together with their isomeric ester derivatives, react with nucleophilic sites on proteins and small endogenous molecules, such as glutathione, which potentially contributes to the observed toxicity and adverse drug reactions associated with some drugs.

5.?Examination of the stability of the 1-O-acyl-β-d-glucuronides of aryl acetic acid, α-carbon substituted aryl acetic acid, aliphatic and aromatic acids, as determined by their first order degradation half-lives, indicates the significance of electronic and steric features that contribute to conjugate stability under physiological conditions.

6.?Examination of the of the electronic properties of the carbonyl carbon atom in acyl glucuronides, as measured by the pKa of the parent acid, together with the steric substituents about the acyl carbonyl provides insight into the reactivity of these conjugates.

7.?The investigations reported herein on a large number of 1-O-acyl-β-d-glucuronides has allowed rationalisation of their physicochemical properties in relation to the structure of the parent drug and has the potential to contribute to the design of carboxylic acid containing drug molecules with increased stability of a major metabolite with potential reduction in toxicity and adverse drug reactions.     

Can we estimate the critical micelle concentration of amphiphilic drug bases from molecular connectivity indices?

Self-aggregation of drugs is since many years an important topic in the pharmaceutical sciences. Drugs can aggregate similar to surfactants and thereby exhibit a critical micelle concentration (CMC). The present work focused on amphiphilic drug bases and it was aimed to predict log(CMC) based on chemical structure alone. A dataset of 35 compounds was gathered mostly form the literature and complemented with own measurements based on ultrasonic resonator technology. The hydrophilic–lipophilic balance (HLB) values of the protonated bases were calculated and provided a range of 22.9–27.4. Based on a hypothesis from surfactant sciences, it was tried to predict log(CMC) with connectivity and shape indices as well as molecular dipole moment. A fairly good model was obtained using the Randix index (RI), 3?D Wiener number (WN) and molecular dipole moment (DM) (R²?=?0.824). Interestingly, a simple linear regression of log(CMC) with the Randic index alone, resulted in an acceptable model (R²?=?0.755). The present work should help with early identification of drug bases that exhibit surfactant-like behavior and an estimation of log(CMC) values is proposed. An improved understanding of drug aggregation and prediction of log(CMC) helps to better cope with physical consequences like, for example, “anomalous” drug solubility in drug discovery and development.     

The effect of chamomile extract obtained in supercritical carbon dioxide conditions on physicochemical and usable properties of pharmaceutical ointments

The study investigated the effect of chamomile extract obtained in supercritical carbon dioxide conditions on the basic properties of pharmaceutical ointments. A total of five formulations were designed and prepared, differing in the weight ratio of sunflower oil to chamomile extract (5:0, 3.5:1.5, 2.5:2.5, 1.5:3.5 and 0:5). An increase in the concentration of chamomile extract was found to be accompanied by a decrease in hardness, adhesive power and flow limit. Based on viscosity measurements it was shown that ointments containing the hydrophobic plant extract under study were prone to larger drops in viscosity under the effect of the set shear rate. It was determined that from the viewpoint of ointment spreadability and application to the skin, the optimum concentration of chamomile extract for the studied formulations should be within the range of 1.5–2.5%. Furthermore, the addition of chamomile extract to ointments was found to give samples a yellow-green color. Green was observed to be the dominant color, and its saturation and shade varied for different formulations.     

纳米制剂在心肌缺血区域的靶向机制及应用

缺血性心脏病是严重威胁人类健康的疾病。至今为止,药物预处理和治疗依旧是心肌缺血预防和治疗的重要手段。但大多数抗心肌缺血药物缺乏组织特异性,同时由于缺血区域血液循环受阻,导致药物在缺血部位的分布往往不甚理想。靶向纳米制剂是一种治疗心血管疾病的新型给药策略。纳米制剂在体内主要可以通过"被动靶向"、"主动靶向"和"物理化学靶向"作用将药物递送至病变部位,提高药物在缺血区域的靶向性和释放率,从而改善药物治疗效果。本文对应用靶向纳米制剂治疗心肌缺血的疗效及机制研究作一综述。     

Solid lipid nanocarriers in drug delivery: characterization and design

Introduction: Solid lipid nanoparticles are promising drug carriers for systemic circulations as well as local applications. One of the major challenges for drug delivery is designing nanocarriers for efficient delivery of active substances to the target site and facilitating drug absorption.

Areas covered: In this article, the effects of excipients and particle preparation methods on the properties of solid lipid nanocarriers (SLNCs) and their impact on drug absorption and efficacies related to different administration routes are reviewed and discussed.

Expert opinion: SLNCs have special characteristics, making them attractive as drug delivery systems, for parenteral and oral delivery for systemic effects, or ocular, pulmonary and topical delivery to enhance local treatment efficacy and reducing systemic side effects. Both excipients and fabrication methods are crucial for the function and size of nanoparticles and should be considered simultaneously in designing particles to obtain the optimal drug absorption and efficacy, especially for local treatments. Despite the demonstrated advantages by the preclinical studies, further studies on improved understanding of the interactions of SLNCs with biological tissues of the target site is necessary for efficient designing functional nanoparticles for clinical applications.

Abbreviations: DG: diglycerides; FFA: free fatty acids; GMS: glyceryl monostearate; MG: monoglycerides; NLC: nanostructured lipid carriers; PL: phospholipids; SLM: solid lipid microparticles; SLN: solid lipid nanoparticles; SLNC: solid lipid nanocarriers; TG: triglycerides.     

Tricalcium silicate cement sealers: Do the potential benefits of bioactivity justify the drawbacks?

BackgroundGrossman described the ideal properties of root canal sealers. The International Organization for Standardization and American National Standards Institute and American Dental Association have codified some of his requirements in ISO 6876 and ANSI/ADA 57, respectively. In this narrative review, the authors combined the ideal Grossman properties and requirements of these standards, emphasizing the newer tricalcium silicate cement sealers. This chemical matrix for such sealers was developed on the basis of the success of bioactive mineral trioxide aggregate–type (tricalcium silicate cement) materials for enhanced sealing and bioactivity.MethodsThe authors searched the internet and databases using Medical Subject Heading terms and then conducted a narrative review of those articles involving the tricalcium silicate cement endodontic sealers.ResultsNinety-four articles were identified that discussed tricalcium silicate cement sealers. Tricalcium silicate cement sealers are partially antimicrobial and have bioactivity, which may presage improved biological sealing of the root canal system. Most other properties of tricalcium silicate cement sealers are comparable with traditional root canal sealers.ConclusionsWithin the limitations of this review, tricalcium silicate cement endodontic sealers met many of the criteria for ideal properties, such as placement, antimicrobial properties, and bioactivity, but limitations were noted in solubility, dimensional stability (shrinkage and expansion), and retrievability.Practical ImplicationsTricalcium silicate–based cements have been commercialized as bioactive, bioceramic endodontic sealers. Warm, cold, and single-cone obturation techniques are usable, depending on the commercial product. Some sealers can cause discoloration and are not easily retrievable, particularly when used to completely obturate a canal.     

多囊卵巢综合征痰湿证的研究进展

多囊卵巢综合征(PCOS)是导致生育期妇女月经紊乱、无排卵性不孕最常见的病因,为妇科常见病。其病因及中医证候分型复杂,以痰湿证最为多见。近年来,结合现代科学技术,众多学者对PCOS痰湿证的本质特征进行了深入研究,对其临床治疗方法进行了多方面的探讨。文章从PCOS痰湿证的病因、证候分布特征、临床表现、理化指标变化及辨证治疗、分期治疗、中西医结合治疗、针灸联合其他治疗等方面对其进行概述,以期分析PCOS痰湿证的临床证候特征,为其临床诊疗提供一定的科学依据。