Z-guggulsterone induces PD-L1 upregulation partly mediated by FXR, Akt and Erk1/2 signaling pathways in non-small cell lung cancer.

Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule, that is overexpressed in non-small cell lung cancer (NSCLC) and has been associated with the response to anti-PD-1/PD-L1 immunotherapy. Z-guggulsterone (Z-GS), an active compound extracted from the gumresin of the Commiphora mukul tree, has been shown to have anti-tumor effects in NSCLC in our previous study. However, whether Z-GS could affect PD-L1 expression levels in tumor cells remains unknown. In this study, we verified the inhibitory effects of Z-GS on NSCLC cell viability and cell cycle progression in vitro, and mouse Lewis lung carcinoma (LLC) tumor growth in vivo. Notably, Z-GS treatment increased PD-L1 surface and mRNA expression levels, and gene transcription in NSCLC cells, in a dose- and time-dependent manner. Mechanistic experiments showed that the upregulation of PD-L1 was mediated, partly by farnesoid X receptor inhibition, and partly by the activation of the Akt and Erk1/2 signaling pathways in Z-GS-treated NSCLC cells. In vivo, Z-GS treatment dose-dependently increased PD-L1 expression levels in mouse LLC tumor models. Overall, our findings demonstrated a promoting role for Z-GS in PD-L1 expression in NSCLC and provided mechanistic insights, that may be used for further investigation into synergistic combined therapies.

[Screening of reference genes based on real-time quantitative PCR analysis in Monochasma savatieri].

Monochasma savatieri belongs to Scrophulariaceae family. It is a facultative parasitic plant distributed in southern China that has been found in Jiangxi, Guangdong, and Fujian provinces. Previous studies on this plant have focused on its chemical constituents and pharmacological effects. The research foundation of molecular biology and functional genomics is still very in-depth, and there is no report on the reference genes. In this study, 6 reference gene(UBQ, GAPDH, AP-2, ACT, TUB and CYP) from transcriptome database, were selected and analyzed in M. savatieri.The experiment mainly involve two variables, soil moisture content and arbuscular mycorrhizal symbiosis(Rhizophagus irregularis). And the different combination of the factors result in a total of 6 treatments.Statistical tools, including GeNorm, NormFinder and Bestkeeper were utilized to assess the suitability of reference genes based on their stability rankings for different treatment. The result showed that the stability of 6 reference genes were significantly different. TUB and GAPDH were the most stable gene, while ACT was the most instable one. The results would provide reliable and optional available reference genes in gene expression analysis of M. savatieri, which has important application value.

Study on Depression Diagnosis Based on TCM Four Diagnostic and Auxiliary Diagnosis ;System / 中国中医药信息杂志

Objective Base on the theory of traditional Chinese medicine (TCM), obtained human diagnostic information available for joint syndrome differentiation is integrated based on subjective and objective combined syndrome differentiation, in the form of data expression of TCM four diagnosis, forms multiple information fusion of open platform for TCM diagnosis and treatment, and provides some revelation for promoting the development of depression and treatment technology. Methods Totally 30 depression patients and 30 normal people were selected according to the inclusion criteria. TCM four diagnostic and auxiliary diagnosis instrument was used to collect information of four diagnosis, and the statistical software was used for the analysis on pulse diagnosis, and information features of digitalized tongue and listening diagnosis of patients in depression group and normal group were studied. Results Compared with depression group, pulse frequency, fluency, and heart rate of normal group were a bit higher than depression group, without statistical significance (P>0.05);There was statistical significance among pulse frequency, strength, tightness, and pulse wave velocity between the normal group and depression group (P<0.05). 30 patients had 6 depression syndrome types:heart-gallbladder qi deficiency (8 cases), phlegm-heat attacking internally (6 cases), fire excess from yin deficiency (6 cases), liver depression forming fire (6 cases), intense heart fire (3 cases), and heart-spleen deficiency (3 cases). Conclusion The results of differences in pulse diagram parameters were consistent with the theory of classical TCM pulse theory. The results of differences in pulse wave velocity conform to the modern medical research conclusion. TCM four diagnostic auxiliary diagnosis and treatment technology can realize the dynamic detection of depression patients with four diagnostic information, and establish diagnostic methods for depression based on digitalized four diagnostic auxiliary diagnosis.

Pollen developmental defects in ZD-CMS rice line explored by cytological, molecular and proteomic approaches.

Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line. BIOLOGICAL SIGNIFICANCE: MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free sterile line Yunnan ZidaoA. In this study, the cytological, molecular and proteomic approaches were used to study the characteristics of this new CMS line. Cytological study indicates the CMS line is aborted at the early uninucleate stage. A potential sterile gene ZD352 is identified in MxA, the protein product of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic analysis is performed to study the relevant proteins involved in the CMS occurance, 45 proteins are found to be significant differentially expressed and these proteins are involved in many cellular processes such as carbohydrate metabolism, stress response, protein synthesis. To our knowledge, this is the first report using the iTRAQ-labeled quantitative proteomic to study the protein expression variation during the abortion processes between a CMS line and its maintainer line. These results provide new insights on the CMS mechanisms of ZD-CMS rice line.

Alterations of mitochondrial protein assembly and jasmonic acid biosynthesis pathway in Honglian (HL)-type cytoplasmic male sterility rice.

It has been suggested that the mitochondrial chimeric gene orfH79 is the cause for abortion of microspores in Honglian cytoplasmic male sterile rice, yet little is known regarding its mechanism of action. In this study, we used a mass spectrometry-based quantitative proteomics strategy to compare the mitochondrial proteome between the sterile line Yuetai A and its fertile near-isogenic line Yuetai B. We discovered a reduced quantity of specific proteins in mitochondrial complexes in Yuetai A compared with Yuetai B, indicating a defect in mitochondrial complex assembly in the sterile line. Western blotting showed that ORFH79 protein and ATP1 protein, an F(1) sector component of complex V, are both associated with large protein complexes of similar size. Respiratory complex activity assays and transmission electron microscopy revealed functional and morphological defects in the mitochondria of Yuetai A when compared with Yuetai B. In addition, we identified one sex determination TASSELSEED2-like protein increased in Yuetai A, leading to the discovery of an aberrant variation of the jasmonic acid pathway during the development of microspores.

[Effects of various planting densities on dynamic growth rhythm and root yield of Isatis indigotica].

OBJECTIVE: To study the effects of various planting densities on dynamic growth and root yield of Isatis indigotica. METHOD: The planting samples were collected to measure the growth period of each organ. RESULT AND CONCLUSION: Under different planting densities, both main root length and breadth exhibited a trend of "fast-slow" by stages. However, the number of individual plant leaves were showed a trend of "slow-fast" on growth period. Meanwhile, the leaf length and breadth were exhibited a trend of "increase-decrease". The increase of dry leaf, dry root and whole plant dry matter was faster during the period of 65-76 days after seeding. The differences of root and leaf yields under various densities were significant. Planting densities has a great effect on yield of root. It must be shown that there was a positive development between the individual plant and colony. According to the dry matter of root and leaf, treatment B (i.e., 7 cm x 25 cm) was good choice.