Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

<p>Abstract</p> <p>Background</p> <p>Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of <it>Cimicifuga dahurica </it>showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of <it>C. dahurica </it>and therefore might eventually be useful in the prevention or treatment of Hepatoma.</p> <p>Methods</p> <p>The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H₂₂hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA <it>in vivo</it>.</p> <p>Results</p> <p>The IC₅₀values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G₀/G₁cell cycle arrest at lower concentration (25 μg/ml), and triggered G₂/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H₂₂tumor in a dose-dependent manner.</p> <p>Conclusion</p> <p>TGA may potentially find use as a new therapy for the treatment of hepatoma.</p

Comparative Study on Mineral-Scale Microcrack Propagation of Shale under Different Loading Methods

Producing a sufficient volume of multiscale crack networks is key to enhancing recovery of shale gas. The formation of crack network largely depends on initiation and propagation of microcracks. To reveal the influence of different loading methods on the propagation of mineral-scale microcracks, this study used the Voronoi tessellation technique to establish a cohesive zone model of shale mineral distribution and applied six different boundary conditions to represent different loading methods. Crack path characteristics, rupture characteristics, continuous crack propagation and turning, and en echelon intermittent crack propagation under different loading methods were compared and analyzed. The essence of different loading methods affecting the length and complexity of cracks was the spreading range of tensile microcracks. The mechanical properties of minerals led to dissimilarities in continuous crack propagation and turning. The formation and propagation of en echelon intermittent fractures of different scales were mainly impacted by the heterogeneity of minerals and mineral aggregates. The spreading direction and connection form of en echelon intermittent fractures were mainly affected by the loading method. Conclusions arising from mineral-scale simulations contribute to understanding the mechanism of microcrack propagation resulting from different loading methods, and these conclusions have a guiding significance to enhanced shale gas recovery

Chemical Constituents, Biological Activities, and Proposed Biosynthetic Pathways of Steroidal Saponins from Healthy Nutritious Vegetable—<i>Allium</i>

Allium is a common functional vegetable with edible and medicinal value. Allium plants have a special spicy taste, so they are often used as food and seasoning in people’s diets. As a functional food, Allium also has abundant biological activities, some of which are used as drugs to treat diseases. By consuming Allium on a daily basis, people can receive active compounds of natural origin, thereby improving their health status and reducing the likelihood of disease. Steroidal saponins are important secondary metabolites of Allium, which are formed by the steroidal aglycone group and sugar. Steroidal saponins have various physiological activities, such as hypoglycemic, antiplatelet aggregation, anti-inflammatory, antitumor, antimicrobial, and enzyme activity inhibition, which is one of the key reasons why Allium has such significant health benefits. The structural diversity and rich biological activities of steroidal saponins make Allium important plants for both food and medicine. In this paper, the chemical structures, biological activities, and structure–activity relationships of steroidal saponins isolated from Allium are reviewed, and the biosynthetic pathways of some key compounds are proposed as well, to provide a molecular reference basis based on secondary metabolites for the health value of Allium

Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer.

The traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. In gelatin zymography assay, Umbelliprenin could inhibit the expression of MMP2 and MMP9 in tumor cells The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. The in vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway

Attitude-Oriented Stability Control with Adaptive Impedance Control for a Wheeled Robotic System on Rough Terrain

Base stability for a wheeled robot while driving over rough terrain is a challenging issue. This paper proposes a novel base-stability control framework, consisting of an AVIC (adaptive variable-impedance control), AVIC-based tracking controller, and a THV (terrain height variation) and AC (attitude control) AC-based controller to stabilize the base on rough terrain. The AVIC-based controller aims to track the desired trajectory of the robot base while suppressing lumped disturbance, including system uncertainties in the internal dynamics and unknown external disturbance. The THV-based controller is utilized as a feedforward controller to improve posture tracking performance in order to achieve a horizontal posture. The AC-based controller is employed to maintain the horizontal posture of the base. The effectiveness and robustness of the proposed controllers are validated by a series of numerical trials, and the results are evaluated

Phase-Engineered VO₂ Metal Nanofiber Enables a Metal–Insulator Transition for Bidirectional Thermal Reallocation

Phase change materials (PCMs) are appealing for their fascinating capability of thermal reallocation, assisting widely in many areas of human productivity and life. However, it has remained a significant challenge to attain shape stability, temperature resistance, and microscale continuity in PCMs while maintaining sufficient phase change performance. Here we report a sol epitaxial fabrication strategy to create metal–insulator transition nanofibers (MIT-NFs) composed of monoclinic vanadium dioxide. The MIT-NFs are further assembled into self-standing two-dimensional membranes and three-dimensional aerogels with structural robustness. The resulting series of metal–insulator transition materials exhibits the integrated features of solid–solid phase change properties, shape stability, and thermal reallocation properties. The integral ceramic characteristic also provides the MIT-NFs with surface stiffness (54 GPa), temperature resistance (−196° to 330 °C), and thermal insulator properties. The successful fabrication of these captivating MIT materials may provide new perspectives for next-generation, shape-stable, and self-standing PCMs

Cryptoporus volvatus extract inhibits influenza virus replication in vitro and in vivo.

Influenza virus is the cause of significant morbidity and mortality, posing a serious health threat worldwide. Here, we evaluated the antiviral activities of Cryptoporus volvatus extract on influenza virus infection. Our results demonstrated that the Cryptoporus volvatus extract inhibited different influenza virus strain replication in MDCK cells. Time course analysis indicated that the extract exerted its inhibition at earlier and late stages in the replication cycle of influenza virus. Subsequently, we confirmed that the extract suppressed virus internalization into and released from cells. Moreover, the extract significantly reduced H1N1/09 influenza virus load in lungs and dramatically decreased lung lesions in mice. And most importantly, the extract protected mice from lethal challenge with H1N1/09 influenza virus. Our results suggest that the Cryptoporus volvatus extract could be a potential candidate for the development of a new anti-influenza virus therapy

Geographical Distribution and Relationship with Environmental Factors of Paphiopedilum Subgenus Brachypetalum Hallier (Orchidaceae) Taxa in Southwest China

The determination of the geographic distributions of orchid species and their relationships with environmental factors are considered fundamental to their conservation. Paphiopedilum subgenus Brachypetalum is one of the most primitive, ornamental, and threatened groups of Orchidaceae. However, little is known about the distribution of Brachypetalum orchids and how they are influenced by environmental factors. In this study, we developed a database on the geographical distribution of Brachypetalum orchids based on a large-scale field investigation in the Guangxi, Guizhou, and Yunnan provinces of southwest China (2019-2020). Using this database, we first adopted the nonparametric Mann-Whitney U test to analyze the differences in the geographical distributions and growth environments of Brachypetalum orchids. In addition, we also used the method of principal component analysis (PCA) to explore distribution patterns of Brachypetalum orchids in relation to environmental factors (topography, climate, anthropogenic disturbance, productivity, and soil) in southwest China. Our results indicated that Brachypetalum orchid species were mainly distributed in the karst limestone habitats of southwest China. In general, there were 194 existing localities with the occurrence of seven target orchids in the investigated area. Of the discovered species in our study, 176 locations (~90.7%) were distributed primarily in the karst habitat. Among them, the range of 780-1267 m was the most concentrated elevation of Brachypetalum orchids. In addition, the findings also suggested that the distribution of Brachypetalum orchids in southwest China was relatively scattered in geographical space. However, the density of the distribution of Brachypetalum orchids was high, between 104 degrees and 108 degrees E and between 25 degrees and 26 degrees N. The results of the Mann-Whitney U test revealed that there are obviously different geographical distributions and growth environments of Brachypetalum in southwest China. More specifically, we found some extremely significant differences (p < 0.001) in elevation, mean diurnal range, precipitation of coldest quarter, solar radiation, and exchangeable Ca2+ between the provinces of southwest China. The PCA analysis revealed that elevation, solar radiation, temperature (mean diurnal range, annual temperature range) and precipitation (precipitation seasonality, precipitation of the warmest quarter) were found to be the most significant factors in determining Brachypetalum orchids' distribution. These findings have implications in assessing conservation effectiveness and determining niche breadth to better protect the populations of these Brachypetalum orchid species in the future