Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

[Relationship between urban atmospheric environment and surrounding two-dimensional and three-dimensional landscape pattern in China.] / æˆ‘å›½åŸŽå¸‚å¤§æ°”çŽ¯å¢ƒä¸Žå‘¨è¾¹åŒºåŸŸäºŒç»´å’Œä¸‰ç»´æ™¯è§‚æ ¼å±€å ³ç³».

Atmospheric environment in urban built-up area is severely influenced by the surrounding landscape pattern. Understanding the relationship between air pollution and surrounding landscape pattern at small scale has great significance for mitigating air pollution from the perspective of urban construction. The annual average concentrations of NO2, SO2, PM2.5 and PM10 from 266 air pollution monitoring stations in 30 provincial capitals of China in 2017 were chosen as dependent variables. Ten two-dimensional and three-dimensional landscape pattern indices (number of buildings, building aggregation, building density, impervious water ratio, quantitative density of catering, building footprint area, high building ratio, floor area ratio, total building area and building type Shannon diversity index) within the 3 km area around the monitoring stations were used as independent variables. The effects of landscape pattern on the concentration of four air pollutants were analyzed using the boosted regression trees model. The results showed that the concentration of four air pollutants in the central and northern cities were significantly higher than that in the southeast coastal cities and southwest cities. The most important factor affecting the concentrations of NO2, SO2, PM2.5 and PM10 was the impervious ratio, with relative contribution rates of 40.7%, 36.3%, 51.0% and 51.8% respectively. The results of sub-region analysis showed that the most important influencing factor differed in different regions, including the impervious ratio in the East and Central China; the number and density of buildings in South China; the impervious ratio and diversity of building types in North China; the impervious ratio and the number of buildings in Northeast China, the density of buildings in Northwest China. Such differences were mainly caused by climate, topography, urban planning, and other factors.

Prevention of infectious diseases through microecology modulation techniques / 华西口腔医学杂志

The microbe is small in volume, but large in quantity and species. The symbiotic microbe, which is far more than human cells, code millions times of genes than human being. Somatic cells and these symbiotic microbe distributing in human body skin, respiratory tract, oral cavity and gastrointestinal tract, urinary tract and other parts form a complex ecosystem whose dynamic balance is highly related to body health. With the successful implementation of Human Microbiome Project, more attentions have been paid to the next generation microbiome technologies. New tools and methods for ecological regulation of human microbiome are emerging. The way we improve the world of human microbiology will be more convenient. This paper will make a review on the modulation techniques of human microbiome.

[Construction of a low-pH-sensing system in Streptococcus mutans].

OBJECTIVE: To construct a low-pH-sensing system in Streptococcus mutans (S. mutans) and to visually detect the pH in situ. METHODS: Promoter of ureaseⅠ(PureⅠ) and green fluorescence protein (gfp) DNA fragments were amplified by polymerase chain reaction (PCR) from the genome of Streptococcus salivarius 57.I and S. mutans containing the gfp fragment. The two amplified DNA fragments were ligated together and further integrated into pDL278 to construct the recombinant plasmid pDL278-pureⅠ-gfp. This recombinant plasmid was then transformed into S. mutans UA159 cells. Subsequently, the intensity of the optical density per unit area of the low-pH-sensing system was measured and compared under different pH conditions and different processing times. RESULTS: PureⅠ and gfp DNA fragments were amplified successfully with the correct molecule sizes (450 and 717 bp, respectively). The recombinant plasmid pDL278-pureⅠ-gfp was constructed and further verified by PCR and sequencing. The intensity of the optical density per unit area of the low-pH-sensing system increased with decreasing pH and increasing processing time. CONCLUSIONS: A low-pH-sensing system was constructed successfully in S. mutans. Our research verified that pureⅠ of Streptococcus salivarius can function well in S. mutans as an acid induced promoter, and provided a new method of detecting the pH of plaque biofilms in situ.

Construction of a low-pH-sensing system in Streptococcus mutans / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To construct a low-pH-sensing system in Streptococcus mutans (S. mutans) and to visually detect the pH in situ.</p><p><b>METHODS</b>Promoter of ureaseⅠ(PureⅠ) and green fluorescence protein (gfp) DNA fragments were amplified by polymerase chain reaction (PCR) from the genome of Streptococcus salivarius 57.I and S. mutans containing the gfp fragment. The two amplified DNA fragments were ligated together and further integrated into pDL278 to construct the recombinant plasmid pDL278-pureⅠ-gfp. This recombinant plasmid was then transformed into S. mutans UA159 cells. Subsequently, the intensity of the optical density per unit area of the low-pH-sensing system was measured and compared under different pH conditions and different processing times.</p><p><b>RESULTS</b>PureⅠ and gfp DNA fragments were amplified successfully with the correct molecule sizes (450 and 717 bp, respectively). The recombinant plasmid pDL278-pureⅠ-gfp was constructed and further verified by PCR and sequencing. The intensity of the optical density per unit area of the low-pH-sensing system increased with decreasing pH and increasing processing time.</p><p><b>CONCLUSIONS</b>A low-pH-sensing system was constructed successfully in S. mutans. Our research verified that pureⅠ of Streptococcus salivarius can function well in S. mutans as an acid induced promoter, and provided a new method of detecting the pH of plaque biofilms in situ.</p>

Comparative analysis of clinical research resources between China and the United States / 军事医学

As an important resource for a country to participate in international high-tech competition in the bio-pharma-ceutical field, clinical research resources play a key role in the multi-center clinical research and the translation from basic research to clinical practice.China has a large population and diverse diseases, but chinical disease research relevant policies and regulations are imperfect.In contrast, the United States has perfect laws and regulations related to clinical research.By comparatively analyzing the disease resource, platform support and regulatory environment between China and the U.S., this article offers suggestions on the development of clinical research resources so as to facilitate the clinical research in China.

An analysis of the New Strategy for American Innovation in health care domains / 军事医学

In October 2015 ,the White House issued a New Strategy for American Innovation which was also concerned with precision medicine initiative , BRAIN initiative and health care .This paper introduces the background , main content and developments of this new strategy ,hoping to facilitate the development of healthcare in China .

Large-scale RNA-Seq Transcriptome Analysis of 4043 Cancers and 548 Normal Tissue Controls across 12 TCGA Cancer Types.

The Cancer Genome Atlas (TCGA) has accrued RNA-Seq-based transcriptome data for more than 4000 cancer tissue samples across 12 cancer types, translating these data into biological insights remains a major challenge. We analyzed and compared the transcriptomes of 4043 cancer and 548 normal tissue samples from 21 TCGA cancer types, and created a comprehensive catalog of gene expression alterations for each cancer type. By clustering genes into co-regulated gene sets, we identified seven cross-cancer gene signatures altered across a diverse panel of primary human cancer samples. A 14-gene signature extracted from these seven cross-cancer gene signatures precisely differentiated between cancerous and normal samples, the predictive accuracy of leave-one-out cross-validation (LOOCV) were 92.04%, 96.23%, 91.76%, 90.05%, 88.17%, 94.29%, and 99.10% for BLCA, BRCA, COAD, HNSC, LIHC, LUAD, and LUSC, respectively. A lung cancer-specific gene signature, containing SFTPA1 and SFTPA2 genes, accurately distinguished lung cancer from other cancer samples, the predictive accuracy of LOOCV for TCGA and GSE5364 data were 95.68% and 100%, respectively. These gene signatures provide rich insights into the transcriptional programs that trigger tumorigenesis and metastasis, and many genes in the signature gene panels may be of significant value to the diagnosis and treatment of cancer.

Land use change influences soil C, N, and P stoichiometry under 'Grain-to-Green Program' in China.

Changes in land use might affect the combined C, N and P stoichiometry in soil. The Grain-to-Green Program (GTGP), which converts low-yield croplands or abandoned lands into forest, shrub, and/or grassland, was the largest land reforestation project in China. This study collected the reported C, N and P contents of soil in GTGP zones to achieve the factors driving the changes in the C:N, C:P, and N:P values. The results showed that the annual average precipitation exerted significant effects on the C:P value, and on the N:P value became significant 20 years after the change in land use. The annual average temperature was the main factor affecting the C:N value during the first 10 years, while the annual average precipitation strongly affected this value afterwards. In addition, "Redfield-like" interactions between C, N, and P in the soil may exist. A linear regression revealed significant positive correlations between the C:N, C:P, and N:P values and the restoration age, temperature, and precipitation after a change in land use. Therefore large-scale changes in land use under the 'GTGP' program might significantly affect the C:N, C:P and N:P ratios in soil.