Construction of an enhanced computed tomography radiomics model for non-invasively predicting granzyme A in head and neck squamous cell carcinoma by machine learning.

PURPOSE: Classical prognostic indicators of head and neck squamous cell carcinoma (HNSCC) can no longer meet the clinical needs of precision medicine. This study aimed to establish a radiomics model to predict Granzyme A (GZMA) expression in patients with HNSCC. METHODS: We downloaded transcriptomic data of HNSCC patients from The Cancer Genome Atlas for prognosis analysis and then used corresponding enhanced computed tomography (CT) images from The Cancer Imaging Archive for feature extraction and model construction. We explored the influence of differences in GZMA expression on signaling pathways and analyzed the potential molecular mechanism and its relationship with immune cell infiltration. Subsequently, non-invasive CT radiomics models were established to predict the expression of GZMA mRNA and evaluate the correlation with the radiomics-score (Rad-score), related genes, and prognosis. RESULTS: We found that GZMA was highly expressed in tumor tissues, and high GZMA expression was a protective factor for overall survival. The degree of B and T lymphocyte and natural killer cell infiltration was significantly correlated with GZMA expression. The receiver operating characteristic curve showed that the Relief GBM and RFE_GBM radiomics models had good predictive ability, and there were significant differences in the Rad-score distribution between the high- and low-GZMA-expression groups. CONCLUSIONS: GZMA expression can significantly affect the prognosis of patients with HNSCC. Enhanced CT radiomics models can effectively predict the expression of GZMA mRNA.

Concentrations and isotopic analysis for the sources and transfer of lead in an urban atmosphere-plant-soil system.

Lead pollution has attracted significant attention over the years. However, research on the transfer of lead between urban atmospheric particles, soils, and plants remains rare. We measured lead concentrations and lead isotope ratios in total suspended particles (TSP), soil, and plants in an urban wetland in Beijing. The study period was September 2016-August 2017- covering all four seasons. The concentrations of lead in the atmospheric particles vary from 3.13 to 6.68 mg/m3. It is significantly higher in autumn than that in spring and summer (P < 0.05). There is also a significant difference between summer and winter (P < 0.05). The soil lead concentrations range from 57 to 114 mg/kg, with the highest concentration in spring, followed by summer, winter and autumn. The lead concentrations are 1.28-7.75 mg/kg in plants. The concentration was highest in spring and significantly higher than in summer. The bioaccumulation factor of Phragmites australis was 0.064 (<0.1), indicating that lead is not easily transferred to plants. Unlike the bioaccumulation factors, translocation factors have much higher values, indicating a higher transfer within the plants. Results also indicate an interesting seasonal pattern with almost 97% of lead in plants during spring being of atmospheric origin, whereas in autumn, soilborne sources contribute almost 94%. The isotopic compositions of lead in the urban atmosphere-soil-plant system show that lead pollution results from the mixing of geogenic and anthropogenic materials. Vehicle exhaust, crustal rocks and ore deposits are likely primary sources of lead pollution within the study domain.

Temporal and spatial changes of Pb in soils in Cuihu wetland, Beijing, China.

Protecting soil from Pb contamination has been a programme for a long time in China. However, research on lead pollution in wetlands remains rare. To understand the characteristics of Pb pollution in Beijing and the sources of contamination of different soil samples in wetlands, we collected samples during all four seasons from two soil horizons and analyzed their Pb concentrations and Pb isotope ratios. The average concentrations of Pb varied from 65.44 mg/kg in spring to 106.11 mg/kg in winter. Concentrations in autumn were significantly lower than those in spring and summer and were notably different between A and B Horizons (59.42 and 71.47 mg/kg, respectively). The Pb isotopic compositions show that Pb pollution results from a mixing of geogenic and anthropogenic materials. The ratios of 206Pb/207Pb and 206Pb/208Pb evidenced that coal combustion and vehicle exhaust are the main sources of lead contamination in the two horizons. These results will help in reducing lead contamination in soil by knowing the temporal and spatial variations and sources of lead in Beijing.

The PM removal process of wetland plant leaves with different rainfall intensities and duration.

Today, particulate-matter (PM) pollution has become one of the most severe air-pollution problems. As the most commonly used method in daily life, phytoremediation can use plant organs (such as leaves) as biological filters for pollutants to repair the atmosphere. At the same time, rainfall can remove PM from plant-leaf surfaces and enable them to adsorb PM again. By simulating natural rainfall, the rainfall characteristics are quantified as rainfall intensity and rainfall duration, and we use the washout-weighing method to obtain the amount of PM removed from the leaf surface. Then, use a scanner to scan the leaves after rain to get their images, and use Image J software to process the images to obtain leaf area. Finally, the amount of PM removed by rain per unit leaf area can be calculated. It will be used to explore the impact of different rainfall intensity and duration on the removal of PM from the leaf surface of wetland plants. The results showed that under three rainfall intensities used in this experiment, the removal of PM from plant-leaf surfaces all increased with an increase in rainfall duration. When the particle size is 10-100-µm, and the rainfall intensity is 30 mm/h, the removal amount of plant particles tested in this experiment is the largest. With increased rainfall duration, the removal of PM from plant-leaf surfaces increased sharply at first, then slowly, and finally tended to be stable. The removal efficiency of PM on the blade surface is most apparent at the early stage of rainfall, and then gradually weakens. Among the four wetland plants tested in this experiment, in the range of 10-100-µm, the number of PM on the leaf surface of Scirpus validus is the largest, and the optimum rainfall intensity is 30 mm/h; in the range of 2.5-10-µm, the number of PM on the leaf surface of Typha orientalis is the largest, and the optimal rainfall intensity is 30 mm/h; in the range of 0.45-2.5-µm, the number of PM on the leaf surface of Iris wilsonii is the largest, and the optimal rainfall intensity is 15 mm/h. Wetland species with high particle accumulation capacity can provide references for vegetation restoration of degraded wetland plants and plant cultivation in constructed wetlands. At the same time, the best rainfall intensity and duration for removing particulate matter on the surface of plant leaves were obtained through experiments, which provided a reference for the design of automatic plant irrigation systems and dust removers in different scenarios.

Understanding PM2.5 concentration and removal efficiency variation in urban forest park-Observation at human breathing height.

To increase our knowledge of PM2.5 concentrations near the surface in a forest park in Beijing, an observational study measured the concentration and composition of PM2.5 in Beijing Olympic Forest Park from 2014 to 2015. This study analyzed the meteorological factors and removal efficiency at 1.5 m above the ground (human breathing height) over the day in the forest. The results showed that the average concentrations of PM2.5 near the surface peaked at 07:00-09:30 and reached their lowest at 12:00-15:00. Besides, the results showed that the annual concentration of PM2.5 in the forest was highest during winter, followed by spring and fall, and was lowest during summer. The main chemical components of PM2.5 near the surface in the forest were SO4 2- and NO3 -, which accounted for 68.72% of all water-soluble ions that we observed. The concentration of PM2.5 in the forest had a significant positive correlation with relative humidity and a significant negative correlation with temperature. The removal efficiency near the surface showed no significant variation through the day or year. In the forest, the highest removal efficiency occurred between 07:00 and 09:30 in summer, while the lowest occurred between 09:30 and 12:00 in winter.

The size and distribution of tidal creeks affects salt marsh restoration.

Salt marshes are changeable and important ecosystems that currently face various threats, including global climate change and human activities. The influence of these factors can result in the degradation of salt marshes. Tidal creeks, which are an important source of nutrients and other substances for salt marsh vegetation, play an important role in the health of salt marshes. In this study, the morphological characteristics of tidal creeks and the characteristics of two typical plants, Suaeda glauca (SG) and Phragmites communis (PC), in the Yellow River Delta, China were investigated to determine the effect of tidal creeks on these plants. Aerial photography and field measurements of tidal creeks were carried out from May to July 2018 in the study area. At the same time, nine line-intercepts were set in the vertical direction of tidal creeks to investigate plants. The results showed that different grades of tidal creek exerted no significant influence on the growth of either S. glauca or P. communis. However, unlike grade, the size of a creek and the distance from it had marked effects on these plants. The cross-sectional area of a tidal creek had a significant positive impact on the density of S. glauca (r = 0.39, p = 0.02). For P. communis, the depth of a tidal creek had a strong correlation with this species' density (r = 0.51, p = 0.04) and height (r = 0.63, p = 0.01). Meanwhile, there was a negative relationship between the distance from tidal creeks and the height of S. glauca (r = -0.52, p = 0.02). Conversely, the height (r = 0 0.90, p = 0.00) and density (r = 0.62, p = 0.01) of P. communis were positively affected by its vertical distance from tidal creeks. We found that the subtidal zone near a tidal creek was more conducive to the recovery and growth of S. glauca, and that areas further away from a tidal creek, located in the intertidal and subtidal zones, were more conducive to the recovery and growth of P. communis. The parameters associated with tidal creeks in the subtidal zone (cross sectional area 4.55 m2, distance 0-10 m) were beneficial for the growth of S. glauca. For P. communis, relevant features in the intertidal and subtidal zones (depth 0.40-0.45 m, distance 20-60 m) are useful. Our results suggest that attention should be paid to the effects of size and distribution of tidal creeks during the process of salt marsh restoration. This work also provides practical guidance for the restoration of native salt marshes in China.

The blocking effect of atmospheric particles by forest and wetland at different air quality grades in Beijing China.

To understand the effect of forests and wetlands on air quality, the PM10 and PM2.5 concentration and meteorological data were collected in the forest and wetland in the Beijing Olympic Forest Park in China from May 2106 to May 2017. The blocking rates of forest and wetland to PMs were calculated under different air quality grades which were divided into six levels base on a technical regulation. And we have got three main conclusions. (1) The diurnal variations of PMs were different in the forest and wetland. It showed a first decrease and then an increase in the forest; the lowest value (PM10 = 40.00 µg/m3, PM2.5 = 5.37 µg/m3) was at approximately 12:00. In the wetlands, the lowest values were recorded at 16:00 (PM10 = 39.63 µg/m3 and PM2.5 = 15.89 µg/m3). (2) Another result showed that the blocking in the forest were significantly higher than that at the wetlands (P < .05), and the blocking effects were much better under lower air quality grades. The blocking rate of PM10 and PM2.5 was the highest when the air quality is excellent in the forest. When it comes to wetland, the highest blocking rate of PM10 appears at good air quality, and the highest of PM2.5 was at serious polluted. (3) In addition, there was negative correlation between PM concentrations and temperature, whereas the correlation between PM concentrations and relative humidity is positive. However, the correlation between blocking and meteorological parameters is weak.

Assessing the spatiotemporal characteristics of dry deposition flux in forests and wetlands.

Forests and wetlands, as two important ecosystems, play a crucial role in reducing the concentration of particulate matters. The main purpose of this study is to reveal the contribution of forest and wetland ecosystems to the reduction of particulate matter. We collected the concentration and meteorological data during the daytime in a forest and a wetland in the Olympic Park in Beijing. The main results are as follows: daily variation in the PM10 and PM2.5 concentration had the similar trend with the lowest value at midday and relatively high values in the morning and at nightfall. In the forest ecosystem, the trend of PM10 concentration at three heights followed the order: 6 m > 10 m > 1.5 m, while that of the PM2.5 followed the order 1.5 m > 10 m > 6 m. In the wetland, PM10 and PM2.5 concentrations at the three heights exhibited the same trend: 10 m > 1.5 m > 6 m. It is a comprehensive impact on concentration which may include vegetation collection rate, meteorological conditions and some kind of human activities. The PM deposition velocity of wetland was higher than that of forest, and showed the highest values in winter both in PM2.5 and PM10. The PM deposition flux in wetland was lower than forest only in autumn, and the value of deposition flux was higher than forest in other seasons. PM concentrations was positively correlated with relative humidity but negatively correlated with temperature and wind velocity.

Effect of the wetland environment on particulate matter and dry deposition.

In Beijing, particulate matter (PM) in the atmosphere, especially PM2.5 and PM10, have attracted public attention because of its adverse effects. A series of studies have investigated the sources and spatial-temporal variation of PM. Wetland has been reported to own the capacity of resolving air problem. To examine the characteristics of the particulate matter in wetlands, the diurnal variation of PM2.5 and PM10 concentrations with respect to two heights (i.e. 1.5 and 10 m, respectively) and three meteorological factors (i.e. wind speed, temperature, and relative humidity, respectively) was monitored in the Cuihu National Wetland Park in Beijing, and the dry deposition velocity and flux were analysed using the above-mentioned data. Results indicated that (1) As for diurnal variation, the PM concentration constantly decreased at 07:00-16:00 and gradually increased at 16:00-18:00. The maximum instantaneous concentration was observed at 07:00-10:00, while the minimum instantaneous concentration was observed at 13:00-16:00. (2) The annual concentration variation of PM followed the order of dry period > wet period > normal period. (3) The particulate concentrations at 10 m were always greater than those at 1.5 m. (4) The PM concentration was positively correlated to the relative humidity and negatively correlated to the temperature. Wind speed exhibited a complex effect on PM concentration. (5) The regulation of dry deposition efficiency followed the order of spring > winter > summer. (6) Wind speed strongly and positively affected the dry deposition velocity of PM10. The effects of temperature and relative humidity on dry deposition were uncertain.

Lead isotope trends and sources in the atmosphere at the artificial wetland.

With the rapid development of industry, studies on lead pollution in total suspended particulate matter (TSP) have received extensive attention. This paper analyzed the concentration and pollution sources of lead in the Cuihu Wetland in Beijing during the period of 2016-2017. The results show that the lead contents in TSP in the Cuihu Wetland were approximately equal in summer and spring, greater in winter, and greatest in autumn. The corresponding lead concentrations were 0.052, 0.053, 0.101, and 0.115 ng/m3, respectively. We compared the 206Pb/207Pb data with other materials to further understand the potential sources of atmospheric lead. The mean values of 206Pb/207Pb from spring to winter were 1.082, 1.098, 1.092, and 1.078, respectively. We found that the lead sources may be associated with coal burning, brake and tire wear, and vehicle exhaust emissions. We also calculated the enrichment factor values for the four seasons, and the values were all much greater than 10, indicating that the lead pollution is closely related to human activities.

Particle removal in polluted cities: Insights from the wash-off process dynamics for different wetland plants.

Particulate matter (PM) in the atmosphere is a threat to human health. Wetland plants were confirmed to accumulate particles on the leaf surface; at the same time, rainfall could wash-off particles and accelerate the whole removal process, however, the dynamic processes occurring during rainfall events on wetland plants remain unclear. In order to provide sustainable strategies for authorities to take measures, we need to figure out how to reduce PM on leave surface by artificial rainfall efficiently. Four wetland species (Scirpus validus, Typha orientalis, Phragmites australis, and Iris wilsonii) were selected to examine for leave surface accumulation and simulate the experiment. We estimated the wash-off ability of rainfalls with three different intensities (15, 30, and 60 mm h-1) and determined the proportions of different PM size-fractions washed by the rains. The results showed that particles accumulated on the surface could be washed off efficiently (78% ∼ 89%) by the simulated rainfalls. The removal rates were high in the first 30 min and large particles comprised a large proportion of the removed particles. The rainfall with the intensity of 30 mm h-1 removed the most particles among three different rainfall intensities. When the rainfall intensity increased, fine particles (PM2.5) could be washed off more easily. Moreover, with a thinner wax layer, fine particles on wetland plants' leaf surfaces might be more easily removed by the rains. While wash off the plants, spraying rains with the intensity of 30 mm h-1 for about 30 min every time (high intensity with shorter time) may be particle removal efficiency.

Influence of fungi and bag mesh size on litter decomposition and water quality.

Litter decomposition is a complex process that is influenced by many different physical, chemical, and biological processes. Environmental variables and leaf litter quality (e.g., nutrient content) are important factors that play a significant role in regulating litter decomposition. In this study, the effects of adding fungi and using different mesh size litter bags on litter (Populus tomentosa Carr. and Salix matsudana Koidz.) decomposition rates and water quality were investigated, and investigate the combination of these factors influences leaf litter decomposition. Dissolved oxygen (DO), chemical oxygen demand (COD), total phosphorus (TP), and ammonia-nitrogen (NH3-N) were measured during the 112-day experiment. The salix leaf litter (k = 0.045) displayed faster decomposition rates than those of populous leaf litter (k = 0.026). Litter decomposition was initially slow and then accelerated; and by the end of the experiment, the decomposition rate was significantly higher (p = 0.012, p < 0.05) when fungi were added to the treatment process compared to the blank, and litter bags with different mesh sizes did not influence the decomposition rate. The variations in the decomposition rates and nutrient content were influenced by litter quality and a number of environmental factors. The decomposition rate was most influenced by internal factors related to litter quality, including the N/P and C/P ratios of the litter. By quantifying the interact effect of environment and litter nutrient dynamic, to figure out the revetment plant litter decomposition process in a wetland system in biological physical and chemical aspects, which can help us in making the variables that determine decomposition rates important for assessing wetland function.

Tumor-derived extracellular vesicles inhibit osteogenesis and exacerbate myeloma bone disease.

Background: As a hallmark driver of multiple myeloma (MM), MM bone disease (MBD) is unique in that it is characterized by severely impaired osteoblast activity resulting from blocked osteogenesis in bone marrow-derived mesenchymal stem cells (BM-MSCs). The mechanisms underlying this preferential blockade are incompletely understood. Methods: miRNA expression of MM cell-derived extracellular vesicles (MM-EVs) was detected by RNA sequencing. MM-EVs impaired osteogenesis and exacerbated MBD were in vitro and in vivo validated by histochemical staining, qPCR and micro-CT. We additionally examined the correlation between CD138+ circulating EVs (cirEVs) count and bone lesion in de novo MM patients. Results: Here, by sequencing and bioinformatics analysis, we found that MM-EVs were enriched in various molecules negatively regulating osteogenesis. We experimentally verified that MM-EVs inhibited BM-MSC osteogenesis, induced elevated expression of miR-103a-3p inhibiting osteogenesis in BM-MSCs, and increased cell viability and interleukin-6 secretion in MM cells. In a mouse model, MM-EVs that were injected into the marrow space of the left tibia led to impaired osteogenesis and exacerbated MBD and MM progression. Furthermore, the levels of CD138+ cirEVs in the peripheral blood were positively correlated with the number of MM bone lesions in MM patients. Conclusions: These findings suggest that MM-EVs play a pivotal role in the development of severely impaired osteoblast activity, which represents a novel biomarker for the precise diagnosis of MBD and a compelling rationale for exploring MM-EVs as a therapeutic target.

Wetlands with greater degree of urbanization improve PM2.5 removal efficiency.

In recent decades, China has experienced both rapid urbanization and heavy air pollution and the rapid urbanization trend would be continue in the next decade. Wetlands have been shown to be efficient in particle removal, primarily through dry deposition and leaf accumulation. Thus, a more comprehensive understanding of PM2.5 removal by wetlands during urbanization processes could inform urban planning. In the current study, three wetland plots, Cuihu Lake Park (CL), Summer Palace (SP), and Olympic Park (OP), were selected as low, medium, and highly degrees of urbanization site respectively based on the proportions of building and traffic district areas to compare the removal efficiencies. Results show the average dry deposition velocity in OP was significantly higher than CL and SP. Dry deposition is mainly influenced by meteorological conditions. Buildings and other infrastructure make the meteorological conditions conducive to deposition, resulting in higher wind velocity, higher temperature, and more intense turbulence between buildings. Variation in leaf accumulation was not statistically significant between the three plots, and plant species was the major factor affecting the amount of accumulation. The dry deposition contribution to particle removal increases with degree of urbanization. The average dry deposition accounted for 39.74%, 52.55%, and 62.75% at low, middle and high level respectively. Therefore, Wetlands with greater degree of urbanization improve PM2.5 removal efficiency primarily by accelerating the dry deposition process. The result emphasizes the importance of wetlands in particle removal in highly urbanized areas and thus more wetlands should be preserved and/or created during urban expansion.

Multi-scale comparison of the fine particle removal capacity of urban forests and wetlands.

As fine particle (FP) pollution is harmful to humans, previous studies have focused on the mechanisms of FP removal by forests. The current study aims to compare the FP removal capacities of urban forests and wetlands on the leaf, canopy, and landscape scales. Water washing and scanning electron microscopy are used to calculate particle accumulation on leaves, and models are used to estimate vegetation collection, sedimentation, and dry deposition. Results showed that, on the leaf scale, forest species are able to accumulate more FP on their leaf surface than aquatic species in wetlands. On the canopy scale, horizontal vegetation collection is the major process involved in FP removal, and the contribution of vertical sedimentation/emission can be ignored. Coniferous tree species also showed stronger FP collection ability than broadleaf species. In the landscape scale, deposition on the forest occurs to a greater extent than that on wetlands, and dry deposition is the major process of FP removal on rain-free days. In conclusion, when planning an urban green system, planting an urban forest should be the first option for FP mitigation.

Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition but Apoptosis in Human Proximal Tubular (HK-2) Cells: Implications for Renal Impairment in Multiple Myeloma.

Renal impairment (RI) is one of the hallmarks of multiple myeloma (MM) and carries a poor prognosis. Microvesicles (MVs) are membrane vesicles and play an important role in disease progression. Here, we investigated the role of MVs derived from MM cells (MM-MVs) in RI of MM. We found that MM-MVs significantly inhibited viability and induced apoptosis, but not epithelial-mesenchymal transition in human kidney-2 (HK-2), a human renal tubular epithelial cell line. The protein levels of cleaved caspase-3, 8, and 9, and E-cadherin, were increased, but vementin levels were decreased in the HK-2 cells treated with MM-MVs. Through a comparative sequencing and analysis of RNA content between the MVs from RPMI8226 MM cells (RPMI8226-MVs) and K562 leukemia cells, RPMI8226-MVs were enriched with more renal-pathogenic miRNAs, in which the selective miRNAs may participate in the up-regulation of the levels of cleaved caspase-3. Furthermore, the levels of CD138+ circulating MVs (cirMVs) in the peripheral blood were positively correlated with the severity of RI in newly-diagnosed MM. Our study supports MM-MVs representing a previously undescribed factor and playing a potential role in the development of RI of MM patients, and sheds light on the potential application of CD138+ cirMV counts in precise diagnosis of RI in MM and exploring MM-MVs as a therapeutic target.

[Effects of RhoA gene silencing by RNA interference on invasion of tongue carcinoma].

OBJECTIVE: To study the effects of RhoA down-regulation by RNA interference on the invasion of tongue carcinoma Tca8113 and SCC-4. METHODS: Determination of the human RhoA sequence as well as the design and constructionof a short specific small interfering RNAs (siRNA) were performed. The siRNA of RhoA gene was transfected into humantongue squamous cell carcinoma Tca8113 and SCC-4 cells line by Lipofectamine 2000. Quantitative real-time polymerasechain reaction was used to examine the mRNA expressionlevels of RhoA. Protein expressions of mRNA, galectin-3,and matrix metalloproteinase (MMP)-9 were evaluated byWestern blot. Transwell invasion assay was performed toassess the invasion ability of tongue carcinoma. RESULTS: RhoA expressions in Tca8113 and SCC-4 cells were reducedsignificantly after transfection of RhoA-siRNA. Protein levels f galectin-3 and MVP-9 were also down-regulated significantly. Invasion ability was inhibited as well. CONCLUSION: RhoA-siRNA can effectively inhibit RhoA expression in Tca8113 and SCC-4 cells. The invasion ability of tongue carcinoma cells decreased with down-regulation of the protein expressions of galectin-3 and MMP-9, indicating that RhoA-siRNA can inhibit invasion of tongue carcinoma. Results show that RhoA may play an important role in the processes of invasion and metastasis of tongue carcinoma.

Siomycin A Induces Apoptosis in Human Lung Adenocarcinoma A549 Cells by Suppressing the Expression of FoxM1.

Forkhead box M1 (FoxM1), a transcription factor of the Forkhead family, is demonstrated to be critical for proliferation, apoptosis, migration and invasion of lung cancer. In this study, we extensively investigated the anticancer effect of siomycin A, which was identified as an inhibitor of FoxM1 transcriptional activity, on human lung adenocarcinoma A549 cells. Our study indicated that treatment with siomycin A resulted in the suppression of FoxM1 expression, which consequently contributed to its effect of cell growth inhibition and cell apoptosis induction in A549 cells. Then the molecular mechanism of siomycin A's apoptotic action on A549 cells was further investigated. The results revealed that siomycin A induced apoptosis by influencing the downstream events of FoxM1, including inhibiting the expression of Bcl-2 and Mcl-1, as well as leading to caspase-3 cleavage. Taken together, our findings may be useful for understanding the mechanism of action of siomycin A on lung cancer cells and provide new insights into the possible application of such a compound in lung cancer therapy in the future.

Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6.

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.

Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway.

Phosphodiesterase 4D (PDE4D) is a subtype of metallohydrolases, and it has been reported that PDE4D functions as a proliferation promoting factor in certain types of cancer, including head and neck cancer. The present study first investigated the function of PDE4D in nasopharyngeal carcinoma (NPC). Western blot analysis was applied to detect PDE4D expression in NPC samples and cells. A lentiviral infection technique was used to stabilize the knockdown of PDE4D, which was subsequently examined in vitro and in vivo. The results showed that PDE4D was overexpressed in the NPC tissues and cells. Knockdown of PDE4D inhibited the growth of CNE2 and 5-8F, inducing cell cycle arrest in the G0/G1 phase in CNE2. These effects could be reversed by epidermal growth factor (EGF) stimulation. Furthermore, knockdown of PDE4D significantly inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and AKT. The results were further validated in an NPC xenograft in nude mice. In conclusion, this study demonstrated that PDE4D may function as a proliferation promoting factor in NPC, by affecting the EGFR/PI3K/AKT signaling pathway. Therefore, the targeting of PDE4D may be a rational strategy in the treatment of NPC.