A multi-herb-combined remedy to overcome hyper-inflammatory response by reprogramming transcription factor profile and shaping monocyte subsets.

Traditional Chinese multi-herb-combined prescriptions usually show better performance than a single agent since a group of effective compounds interfere multiple disease-relevant targets simultaneously. Huang-Lian-Jie-Du decoction is a remedy made of four herbs that are widely used to treat oral ulcers, gingivitis, and periodontitis. However, the active ingredients and underlying mechanisms are not clear. To address these questions, we prepared a water extract solution of Huang-Lian-Jie-Du decoction (HLJDD), called it as WEH (Water Extract Solution of HLJDD), and used it to treat LPS-induced systemic inflammation in mice. We observed that WEH attenuated inflammatory responses including reducing production of cytokines, chemokines and interferons (IFNs), further attenuating emergency myelopoiesis, and preventing mice septic lethality. Upon LPS stimulation, mice pretreated with WEH increased circulating Ly6C- patrolling and splenic Ly6C+ inflammatory monocytes. The acute myelopoiesis related transcriptional factor profile was rearranged by WEH. Mechanistically we confirmed that WEH interrupted LPS/TLR4/CD14 signaling-mediated downstream signaling pathways through its nine principal ingredients, which blocked LPS stimulated divergent signaling cascades, such as activation of NF-κB, p38 MAPK, and ERK1/2. We conclude that the old remedy blunts LPS-induced "danger" signal recognition and transduction process at multiple sites. To translate our findings into clinical applications, we refined the crude extract into a pure multicomponent drug by directly mixing these nine chemical entities, which completely reproduced the effect of protecting mice from lethal septic shock. Finally, we reduced a large number of compounds within a multi-herb water extract to seven-chemical combination that exhibited superior therapeutic efficacy compared with WEH.

Luteoloside Inhibits Proliferation and Promotes Intrinsic and Extrinsic Pathway-Mediated Apoptosis Involving MAPK and mTOR Signaling Pathways in Human Cervical Cancer Cells.

Cervical cancer is a common gynecological malignancy with high incidence and mortality. Drugs commonly used in chemotherapy are often accompanied by strong side-effects. To find an anti-cervical cancer drug with high effects and low toxicity, luteoloside was used to treat the cervical cancer cell line Hela to investigate its effects on cell morphology, proliferation, apoptosis, and related proteins. The study demonstrated that luteoloside could inhibit proliferation remarkably; promote apoptosis and cytochrome C release; decrease the mitochondrial membrane potential and reactive oxygen species level; upregulate the expression of Fas, Bax, p53, phospho-p38, phospho-JNK, and cleaved PARP; downregulate the expression of Bcl-2 and phospho-mTOR; activate caspase-3 and caspase-8; change the nuclear morphology, and fragmentate DNA in Hela cells. These results strongly suggest that luteoloside can significantly inhibit the proliferation and trigger apoptosis in Hela cells. In contrast, luteoloside had less proliferation inhibiting effects on the normal cell lines HUVEC12 and LO2, and minor apoptosis promoting effects on HUVEC12 cells. Furthermore, the luteoloside-induced apoptosis in Hela cells is mediated by both intrinsic and extrinsic pathways and the effects of luteoloside may be regulated by the mitogen-activated protein kinases and mTOR signaling pathways via p53.

Insight on immune cells in rejection and infection postlung transplant.

OBJECTIVE: The aim of this study is to provide a concise overview of the role of immune cells in rejection and infection after lung transplantation. METHODS: Based on previous clinical and basic studies, the role of various types of immune cells in the development of rejection and infection after lung transplantation is summarized. RESULTS: Immune cell functional status is strongly associated with common complications after lung transplantation, such as primary graft dysfunction, infection and occlusive bronchitis syndrome. Targeted balancing of immune cell tolerance and rejection is an important tool for successful lung transplantation. CONCLUSION: A comprehensive understanding of immune cell function and the mechanisms that balance immune tolerance and immune rejection may be a crucial factor in improving survival after lung transplantation.

Computational fluid dynamics simulation analysis of the effect of curved rice leaves on the deposition behaviour of droplets.

BACKGROUND: Although previous studies on the droplet deposition behaviour of rice leaves have modelled the leaves as flat surface structures, their curved surface structures actually have a significant effect on droplet deposition. RESULTS: In this paper, the statistical distribution of the coordinate parameters of rice leaves at the elongation stage was determined, computational fluid dynamics (CFD) simulation models of droplet impact on rice leaves with different curvature radii were built, and the effect of leaf curvature radius on the deposition behaviour and spreading diameter of droplets on rice leaves was studied using validated simulation models. The results showed that the average relative errors of the CFD simulation models were in the range of 2.23-9.63%. When the droplets struck the rice leaves at a speed of 4 m/s, the 50 µm droplets did not bounce within the curvature radii of 25-120 cm, the maximum spreading diameters of 200 and 500 µm droplets that just adhered to the leaves were 287 and 772 µm, respectively. The maximum spreading diameters of 50, 200, and 500 µm droplets that just split were 168, 636, and 1411 µm, respectively. As the curvature radii of the leaves increased, the maximum spreading diameter of the droplets gradually decreased, and droplet bouncing was more likely to occur. However, a special case in which no significant change in the maximum spreading diameter arose when 50 µm droplets hit a leaf with a curvature radius exceeding 50 cm. CONCLUSION: Splitting generally occurred for large droplets with a small curvature radius and small tilt angle; bouncing generally occurred for large droplets with a large curvature radius and large tilt angle. When the droplet was small, the deposition behaviour was mostly adhesion. The change in spreading diameter after stabilisation was similar to the change in maximum spreading diameter, where the spreading diameter after stabilisation greatly increased after droplet splitting. This paper serves as a reference for the study of pesticide droplet deposition and its application in rice-plant protection.

Immunohistochemistry analysis of Pygo2 expression in central nervous system tumors.

Pygo2 as a Wnt signaling pathway component has been detected in multiple cancer types. In this study, we identified Pygo2 expression features by immunohistochemistry in 73 central nervous system tumor specimens, in comparison with 14 normal brain tissues and surrounding non-tumorous tissues of tumor. Our study indicated that 59% of the patient tumor specimens exhibited positive Pygo2-staining and increases intensity with the grade of malignancy, especially for WHO grade III and IV gliomas, was observed high level expression, compared with normal brain tissues. Five out of nine WHO grade III anaplastic astrocytomas and seven out of nine WHO grade IV glioblastomas showed Pygo2-positive staining. The analysis of Pygo2 gene expression by quantitative real-time PCR of additional ten fresh patient samples yielded similar results. Further studies performed with stable cell lines in vitro demonstrated that Pygo2 render cells higher proliferation rate, migration and anchorage-independent colony-forming ability in soft agar. Taken together, our studies suggest an important role of Pygo2 in brain tumor progression.