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Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

Iron coated carbon nanotube (CNT) nanocomposite absorbents were prepared by a metal organic chemical vapor deposition method using carbonyl iron as the Fe precursor. The microstructures and electromagnetic properties of the composites were characterized by XRD, FESEM, TEM, and a vector network analyzer. Results show that the morphology and microwave absorption properties of these core-shell composites are controlled by changing the deposition temperature. The number of iron nanoparticles deposited on the surface of the CNTs gradually increases with increasing deposition temperature in the range 210–240 oC. Too high a temperature (270 oC) causes agglomeration of the Fe nanoparticles on the surface of the CNTs. When the thickness of the electromagnetic coating is 2.9 mm, the composite prepared at 240 oC has the best microwave absorption, with a maximum absorption bandwidth of 6.1 GHz (10.2-16.3 GHz), a minimum reflectivity of −28.3 dB and an absorption intensity less than −10 dB at 6.1 GHz.

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (β-amino ester) (QPBAE-C

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening peopleapos;s health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.

Celastrol, a natural bioactive ingredient derived from Tripterygium wilfordii Hook F, exhibits significant broad-spectrum anticancer activities for the treatment of a variety of cancers including liver cancer, breast cancer, prostate tumor, multiple myeloma, glioma, etc. However, the poor water stability, low bioavailability, narrow therapeutic window, and undesired side effects greatly limit its clinical application. To address this issue, some strategies were employed to improve the anticancer efficacy and reduce the side-effects of celastrol. The present review comprehensively focuses on the various challenges associated with the anticancer efficiency and drug delivery of celastrol, and the useful approaches including combination therapy, structural derivatives and nano/micro-systems development. The specific advantages for the use of celastrol mediated by these strategies are presented. Moreover, the challenges and future research directions are also discussed. Based on this review, it would provide a reference to develop a natural anticancer compound for cancer treatment.

The aim of this paper was to study the prescription compatibility connotation in the treatment of primary dysmenorrhea(PD) and verify the mechanism as predicted by network pharmacology of Siwu Decoction(SWD). Mice PD model was constructed by using estradiol benzoate-oxytocin. PD mice were randomly divided into 8 groups, namely normal group, model group, positive group, complete formula group, Rehmanniae Radix Praeparata-free group, Paeoniae Radix Alba-free group, volatile oil-free group, Chuan-xiong Rhizoma and Angelicae Sinensis Radix-free group. Latent time, writhing times, inhibition rate, prostaglandin F_2_α(PGF_2_α) and prostaglandin E_2(PGE_2) levels in serum, endothelin-1, Ca~(2+), expression levels of prostaglandin synthase 2 G/H(PTGS2), estrogen receptor(ESR1), glucocorticoid receptor gene(NR3 C1) mRNA and protein expression levels in the uterus homogenate and pathological changes of uterine tissue were index to explore the prescription compatibility connotation and verify the mechanism of SWD in the treatment of PD. Compared with the extraction liquid of the whole recipe, the effect of Rehmanniae Radix Praeparata-free group and Paeoniae Radix Alba-free group with volatile oil were slightly lower, the effect of essential oil-free group was significantly lower, and the effect of Chuanxiong Rhizoma and Angelicae Sinensis Radix-free group was worse than that of the whole recipe. The relative expression levels of PTGS2 protein and mRNA were significantly reduced by the SWD. The relative expressions of protein and mRNA of ESR1, NR3 C1 were significantly increased. SWD treats PD by regulating the expression of key proteins PTGS2, ESR1 and NR3 C1.Its main medicinal herbs were Angelicae Sinensis Radix and Chuanxiong Rhizoma. Active components were mainly in volatile oil, but Paeo-niae Radix Alba and Rehmanniae Radix Praeparata also had some contributions.

Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis. In recent years, it has been demonstrated that NgBR plays an important role in human pathophysiological processes, including lipid metabolism, angiogenesis, N-glycosylation, cell apoptosis, chemoresistance in human hepatocellular carcinoma, and epithelial-mesenchymal transition. The pathophysiologic effects of NgBR have garnered increased attention, and the detection and enhancement of NgBR expression may be a novel approach to monitor the development and to improve the prognosis of relevant human clinical diseases.

The Sertoli cell, which is the supporting cell of spermatogenesis, has an important role in the endocrine and paracrine control of spermatogenesis. Functionally, it provides the cells of the seminiferous epithelium with nutrition, conveys mature spermatids to the lumen of seminiferous tubules, secretes androgen‑binding protein and interacts with endocrine Leydig cells. In addition, the levels of cholesterol, as well as its intermediates, vary greatly between nongonadal tissues and the male reproductive system. Throughout spermatogenesis, a dynamic and constant alteration in the membrane lipid composition of Sertoli cells occurs. In several mammalian species, testis meiosis‑activating sterol and desmosterol, as well as other cholesterol precursors, accumulate in the testes and spermatozoa. In addition, certain cholesterogenic genes exhibit stage‑specific expression patterns during spermatogenesis, including the cytochrome P450 enzyme lanosterol 14α‑demethylase. Inconsistency in the patterns of gene expression during spermatogenesis indicates a cell‑type specific and complex temporary modulation of lipids and cholesterol, which also implicates the dynamic interactions between Sertoli cells and germ cells. Furthermore, in the female reproductive tract and during epididymal transit, which is a prerequisite for valid fertilization, the modulation of cholesterol occurring in spermatozoal membranes further indicates the functional importance of sterol compounds in spermatogenesis. However, the exact role of cholesterol metabolism in Sertoli cells in sperm production is unknown. The present review article describes the progress made in the research regarding the characteristics of the Sertoli cell, particularly the regulation of its cholesterol metabolism during spermatogenesis.

To evaluate the pharmacodynamic effect of Siwu Decoction in treating blood deficiency in mice under multidimensional pharmacodynamic indexes by factor analysis. The mouse blood deficiency model was established with cyclophosphamide combined with acetophenone; and mouse organ index,white blood cells,red blood cell,hemoglobin,platelet counts in whole blood,serum granulocyte-macrophage colony-stimulating factor,macrophagecolony-stimulating factor,promotion erythropoietin,interleukin-3 and interleukin-6 were used as indicators to characterize the blood-enriching effect of Siwu Decoction; the pharmacodynamic effect of Siwu Decoction on blood deficiency model was evaluated comprehensively by factor analysis. Four common factors were extracted from 14 pharmacodynamics indexes through the factor analysis,namely blood phase factor,viscera index,hematopoietic regulatory factor 1-spleen index and hematopoietic regulatory factor 2-viscera index. The cumulative contribution rate of variance reached 86. 581%. The comprehensive score of factor analysis showed that Siwu Decoction had the best effect on blood replenishment,and it is significant compared with the model group( P0. 01). The effect of alcohol precipitation of Siwu Decoction was slightly decreased. The study showed that Siwu Decoction has the best blood-enriching effect,followed by water decoction and traditional decoction. Alcohol precipitation had the worst effect. Factor analysis can be used for the comprehensive evaluation of blood deficiency mice model,and is a suitable evaluation method for animal model for multi-dimensional multistage complex data analysis. It provides a new model to evaluate the efficacy of multidimensional data in the future.

Nowadays,the advantages of traditional Chinese medicine(TCM) for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity. Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body. Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning. It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors. Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs. In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.

This paper aimed to predict and explore the mechanism of multiple components, targets and pathways of Siwu decoction for treatment of primary dysmenorrhea, and to establish a network pharmacological model of "compound-target-pathway-disease". According to the active ingredients in Siwu Decoction, Swiss Target Prediction server was used to predict the active component targets based on the reverse pharmacodynamic group matching method, and the primary dysmenorrhea targets approved by FDA were selected by database including DrugBank, OMIM and TTD. According to the enrichment analysis of the target pathways by using KEGG, the Cytoscape software was used to construct the network of "compound-target-pathway-disease" of Siwu Decoction. Network analysis showed that there were 20 active components involved in 114 pathways. And 16 components, 16 target proteins and 24 pathways were related to primary dysmenorrhea. Siwu Decoction may play a role in treating primary dysmenorrhea by acting on protein targets and pathways related to hormone regulation, central analgesia, spasmolysis,inflammation and immunity. This study revealed the potential active compounds and possible mechanism of Siwu Decoction for treatment of primary dysmenorrhea, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Siwu Decoction.

Background Fuzi-Lizhong pill (FZLZP), which was first recorded in the Classic–“Taiping Huimin Heji Ju Fang” of the Song Dynasty, has been widely used to treat gastrointestinal disease in clinic for thousands of years in China. However, an in-depth understanding of the chemical constituents of FZLZP and its potential bioactive constituents is lacking. Methods A simple, sensitive and selective method of high-performance liquid chromatography coupled with quadrupole-time-of-flight high-definition mass spectrometry (HPLC-Q-TOF/MS) and automated data analysis (Agilent MassHunter Qualitative Analysis B.06.00 Workstation Software) was developed to simultaneously identify the chemical constituents of FZLZP and the absorbed prototypes as well as the metabolites in rat serum after the oral administration of FZLZP. Results Sixty-seven compounds, including alkaloids, flavonoids, triterpenes, gingerols, phenylpropanoids and volatile oil, in the FZLZP extract were tentatively characterized by comparing the retention time and mass spectrometry data and retrieving the reference literatures. Additionally, 23 prototype compounds and 3 metabolites in the rat serum samples were identified after oral administration of FZLZP, which might be the potential active components in vivo. In addition, the absorption of alkaloids decreased when Aconitum carmichaeli Debx. was in the form of combined application as a prescription compared to when it was in the form of herb powder. Conclusions Herein, the chemical constituent in vitro and the absorbed compounds in the serum of a traditional Chinese formula, Fuzi-Lizhong pill, were fully characterized using a rapid and comprehensive analysis approach based on high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry coupled to MassHunter Qualitative Analysis software data processing approach. The results provide helpful chemical information on FZLZP for further pharmacology and active mechanism research. In view of the bioactive constitutes that basically were derived from these absorbed compounds in vivo, this work could provide a useful strategy to explore the bioactive substances of traditional Chinese medicine. Electronic supplementary material The online version of this article (10.1186/s13020-019-0227-z) contains supplementary material, which is available to authorized users.

Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in anti-UC.

Apolipoprotein M (apoM) is a relatively novel apolipoprotein that plays pivotal roles in many dyslipidemia-associated diseases; however, its regulatory mechanisms are poorly understood. Many cytokines have been identified that down-regulate apoM expression in HepG2 cells, among which transforming growth factor-β (TGF-β) exerts the most potent effects. In addition, c-Jun, a member of the activated protein 1 (AP-1) family whose activity is modulated by c-Jun N-terminal kinase (JNK), decreases apoM expression at the transcriptional level by binding to the regulatory element in the proximal apoM promoter. In this study, we investigated the molecular mechanisms through which TGF-β decreases the apoM level in HepG2 cells. The results revealed that TGF-β inhibited apoM expression at both the mRNA and protein levels in a dose- and time-dependent manner and that it suppressed apoM secretion. These effects were attenuated by treatment of cells with either SP600125 (JNK inhibitor) or c-Jun siRNA. 5Z-7-oxozeaenol [(a TGF-β-activated kinase 1 (TAK-1) inhibitor)] also attenuated the TGF-β-mediated inhibition of apoM expression and suppressed the activation of JNK and c-Jun. These results have demonstrated that TGF-β suppresses apoM expression through the TAK-1-JNK-c-Jun pathway in HepG2 cells.

Background Therapeutic regimens of breast cancer treatment are increasingly inclined to adopt combination strategy based on the broad spectrum antitumor effect of doxorubicin (Dox). Currently, combination therapy comprises of conventional anti-cancer drugs and angiogenesis inhibitors have been corroborated as an effective approach in cancer treatment. Purpose We explored the ability of a natural anti-angiogenic compound glycyrrhetinic acid (GA), derived from an edible-medicinal herb licorice, to enhance the breast cancer suppression effect of Dox. Study design The drug ratio of GA and Dox with synergistic anticancer effect against MCF-7 cells was optimized by combination index (CI) value in vitro, followed by evaluation of the improved anticancer effects and reduced side-effects of this combination in vitro and in vivo. Methods Cell viability was measured by MTT assay. Analyses of mitochondrial membrane potential and cell apoptosis on MCF-7 cells were performed by JC-1 dye and Annexin V-FITC/PI assays. The cellular accumulation of Dox when combined with GA was evaluated. Levels of apoptosis-related proteins in MCF-7 cells were measured by Western blot analysis. Synergistic anti-angiogenic effects on HUVECs were evaluated. A breast cancer mouse model was established to investigate the anti-tumor effects in vivo. Results Based on the optimization by CI value, Dox and GA at 1:20 molar ratio was chosen as the optimal combination drug ratio that exhibited synergistic effect against MCF-7 breast cancer cells. In addition, the combination of GA and Dox exhibited significantly enhanced cytotoxicity, apoptosis, and loss of mitochondrial membrane potential via the upregulation of a mitochondrial-dependent apoptosis pathway against MCF-7 cells. Interestingly, the addition of GA increased the intracellular accumulation of Dox in MCF-7 cells. Moreover, VEGF-induced HUVECs proliferation, migration, and tube formation were strongly inhibited by Dox when used with GA via the significant down-regulation of VEGFR2-mediated pathway, indicating that the combination of Dox and GA could exhibit ideal synergistic anti-angiogenesis effect. Expectedly, the enhanced anti-tumor efficacy of Dox and reduced Dox-induced cardiotoxicity when used in combination with GA were evident in a mouse breast tumor model. Conclusions These findings support that the combination of Dox with GA is a novel and promising therapeutic strategy for the treatment of breast cancer.

Background: Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment. Methods: We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger's and Begg's tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0. Results: Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25–1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13–1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08–1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24–0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66–1.28). Conclusion: Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.

Curcumin (CUR) is a promising edible phytochemical compound with ideal ulcerative colitis (UC) treatment activity; however, it is characteristically instable in the digestive tract and has a short retention time in colon. Therefore, we designed and fabricated an oral food-grade nanocarrier composed of tannic acid (TA)-coated, Genipin (Gnp)-crosslinked human serum albumin (HSA) to encapsulate CUR (TA/CUR-NPs). The resulting CUR nanoparticles (NPs) were about 220 nm and −28.8 mV. With the assistance of TA layer and Gnp-crosslinking, the entire nano-scaled system effectively delayed CUR release in simulated gastric fluid, prolonged its colon adhesion and increased its uptake in Caco-2 cells. As expected, TA/CUR-NPs oral administration significantly alleviated colitis symptoms in DSS-treated mice when compared with controls by inhibiting the TLR4-linked NF-κB signaling pathway. Collectively, this study indicates that we have developed a convenient, eco-friendly, nano-scaled vehicle for oral delivery of CUR with anti-UC benefit.

Bletilla striata has been largely used in traditional folk medicine in China as a wound healing agent and to treat gastritis and several other health problems. Some studies have shown that plant polysaccharides may have the ability to promote wound healing. The aim of this work was to evaluate the wound healing activity of the polysaccharide extracted from Bletilla striata. Firstly, a Bletilla striata polysaccharide was extracted by water extraction and alcohol precipitation and characterized by Fourier transform infrared spectroscopy. The Bletilla striata polysaccharide was then tested for cell migration and proliferation using the mouse fibroblast cell line. Then, the Bletilla striata hydrogel was fabricated for acute wound health care of the mouse full-thickness excision. The results showed that the BSP enhanced the proliferation and migration of L929 cells. The superior wound healing capacity of the BSP hydrogel was demonstrated that it significantly accelerated the wound healing process in vivo in full-thickness skin defect wounded models. Compared to the saline group, the BSP hydrogel could accelerate wound healing and promote re-epithelialization and collagen deposition by means of TGF-β/Smad signal pathway activation. Taken together, BSP hydrogel would be a useful pharmaceutic candidate for acute cutaneous wound health care.

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for

Traditional Chinese medicine(TCM) pill, the most representative and successive dosage form, is called as one of the four classical TCM dosage forms. "Pills could keep the lasting and lenitive therapeutic efficacy for a long period" is the most classical dosage form theory, showing a guidance significance in making recipe, preparations and clinic application. In this article, we would elucidate the inheritance and development significance of TCM pills in three key points, including dosage form theory, pharmaceutical preparation technology and clinic usage based on the pharmaceutics connotation of this theory. From this, it can provide the basis for researches on pills mechanism, material basis and mode of action in clinical application.

In this article we proposed an improved Super-SBM model dealing with undesirable outputs under the weak disposability assumption of undesirable outputs. Energy efficiencies of various industrial sectors in China from 2001 to 2010 are measured based on this model, and the influencing factors for energy efficiency are explored by Tobit regression model. Empirical results show that, during “The Eleventh Five-year Plan”, energy efficiency of each industrial sector and category has been improved to various extents, but overall efficiency variations among industries have not taken on a convergence trend. Light industry has achieved the highest energy efficiency, followed by heavy industry; while the energy efficiency of the latter has a faster growth rate compared with that of light industry; the gap between these two industries' energy efficiency has been reduced. Energy efficiency variation presents an obvious feature of industrial economy transformation. The analysis of influencing factors show that enterprise scale, industry concentration, industrial property rights structure, and government regulation all affect energy efficiency apparently, but their effects vary across industries. Lastly, based on research results, this paper gives some policy recommendations on improving energy efficiency of the industrial sectors in China.

To investigate the effect and mechanism of serum amyloid A (SAA) on the expression of scavenger receptor class B type I (SR-BI) and inflammatory response in THP-1 macrophages, the human THP-1 cells were treated with SAA and p38-MAPK agonist (anisomycin) or p38-MAPK inhibitor (SB203580). Then, the expressions of SR-BI, phosphorylated p38-MAPK and inflammatory factors (MCP-1, TNF-α, IL-1β) were examined by real-time quantitative PCR, Western blotting and ELISA, respectively. The results showed that, compared with control group, SAA increased the levels of inflammatory factors (MCP-1, TNF-α, IL-1β), down-regulated the expressions of SR-BI, and up-regulated the expression of phosphorylated p38-MAPK protein in a concentration- and time-dependent manner in THP-1 cells (P0.05). After treatment with SAA and p38-MAPK agonist (anisomycin) in THP-1 cells, the expression of SR-BI was down-regulated, and the levels of inflammatory factors and phosphorylated p38-MAPK protein expression were increased, compared with the group only treated by SAA (P0.05). In contrast, the SR-BI expression was up-regulated, whereas inflammatory factors and phosphorylated p38-MAPK protein expressions were decreased after the cells were treated with SAA and p38-MAPK inhibitor (SB203580) (P0.05). The results suggest that SAA-promoted inflammatory response in THP-1 macrophages may be through the phosphorylation of p38-MAPK and inhibition of SR-BI expression.

Dihydrodipicolinate synthase (DHDPS) is the main enzyme of a specific branch of the aspartate pathway leading to lysine biosynthesis in higher plants. We have cloned and characterized the DHDPS gene from Zizania latifolia Griseb, which was named ZlDHDPS. Sequence analysis indicates that it contains an ORF of 954 bp interrupted by two exons and one intron encoding a polypeptide of 317 amino acids lacking a plastid transit peptide and a stop codon. The sequence of ZlDHDPS has high identity with known plant DHDPS in GenBank. Southern blotting analysis indicates that there are two copies of Z. latifolia DHDPS (ZlDHDPS) gene in the Z. latifolia nuclear genome. RT-PCR analysis shows the expression of ZlDHDPS is tissue specific and high level expression is present in fast-growing tissue and reproductive tissue. The 5′-regulatory sequence of ZlDHDPS contains a GT-1 box and a (CA)n element, which may play a role in regulating the expression of ZlDHDPS. The fusion construct of the ZlDHDPS sequence with the reporter gene GUS was transiently expressed in the onion epidermal cells by particle gun-mediated bombardment suggesting that ZlDHDPS was located in the cytoplasm, different from DHDPS gene of other species. Functional complementary analysis showed that ZlDHDPS can recover the DHDPS-deleted mutant of Escherichia coli.

With the unceasing appearance and widespread application of new surveying technology, the present age mining survey has meet huge change. However, lots of problems occurred while using the new techniques since the number of mine is large in China and condition of the mine district is complex, it in some sense influenced the mine exploitation and management of China. Summarized the present situation of new technical application in mining survey, including the advanced instrumentation equipment, the “3S” technology, the information and the network technology and the information fusion technology and so on, and analyzed the problems which exists in the current mining survey, it also provided new ways to present age mining survey from the sustainable development angle.

Atherosclerosis is a major cause of coronary artery disease, which is characterized by cellular lipid accumulation. Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism. Studies have shown that macrophage-derived LPL exhibits proatherogenic properties, and plays a major role in lipid accumulation in macrophages. Evidence suggests that oxidative stress can effectively enhance macrophage LPL production. Betulinic acid (BA) is a pentacyclic lupane triterpene with a potent antioxidant activity. In this study, we investigated whether BA affects the expression of macrophage LPL and how it regulates cellular lipid accumulation.We revealed that BA downregulated H2O2-simulated macrophage LPL protein, mRNA levels and its activity in both concentration- and time-dependent manners. Furthermore, BA decreased LPL-involved total cholesterol and triglyceride levels in macrophages. In addition, cellular lipid staining by Oil Red O showed that BA decreased cellular lipid droplet deposition. Next, we confirmed that pretreatment with BA decreased H2O2-induced production of intracellular reactive oxygen species in a concentration-dependent manner. Further studies demonstrated that BA inhibited H2O2-induced membrane translocation of PKC, phosphorylation of ERK1/2 and c-Fos. Finally, the induction of LPL production and activity by H2O2 was abolished by BA, inhibition of PKC or ERK or depletion c-Fos, respectively.BA, through its role of antioxidant activity, attenuated macrophage-derived LPL expression and activity induced by oxidative stress, and effectively reduced cellular lipid accumulation, likely through inhibition of the pathways involving PKC, ERK and c-Fos. These effects of BA may contribute to its mitigation of atherosclerosis and help develop BA as a therapeutic compound in treatment of atherosclerosis.

Objectives ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. This study was to determine the effects and potential mechanisms of Chlamydia pneumoniae ( C. pneumoniae ) on ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells. Methods and results C. pneumoniae significantly decreased the expression of ABCA1 and reduced cholesterol efflux. Furthermore, we found that C. pneumoniae suppressed ABCA1 expression via up-regulation of miR-33s. The inhibition of C. pneumoniae -induced NF-κB activation decreased miR-33s expression and enhanced ABCA1 expression. In addition, C. pneumoniae increased Toll-like receptor 2 (TLR2) expressions, inhibition of which by siRNA could also block NF-κB activation and miR-33s expression, and promot the expression of ABCA1. Conclusion Taken together, these results reveal that C. pneumoniae may negatively regulate ABCA1 expression via TLR2-NF-κB and miR-33 pathways in THP-1 macrophage-derived foam cells, which may provide new insights for understanding the effects of C. pneumoniae on the pathogenesis of atherosclerosis.

ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.

beta-1,3-glucanase(BG2) is one of the pathogensis-related-proteins(PR). Study of these proteins and their related genes is one of the hot points in plant genetic engineering of disease resistance for a long time. In this research, specific primers were designed with the enzyme cleavage site of Spe I in its forward one and Not I site in the backward according to the BG2 gene sequence. Using this pair of primers, BG2 gene, which was contained in the plasmid of pRTL2, was amplified and confirmed by sequencing the amplified fragment inserted into T-easy vector. The positive clone containing BG2 gene was digested with the enzymes of Spe I/Not I and then BG2 gene was inserted into the Xba I/Not I sites of super expression binary vector pATC940. The reconstructed expression vector named as pATCBG2 was introduced into the wheat of Longfumai10 and Longfumai3 (Triticum aestivum L. em. Thell) through the particle gun transformation method. The Kanamysin resistant (Km') transformants were obtained. PCR, Dot-blotting and PCR-Southern hybridization analysis showed that the BG2 gene was integrated into the genome of wheat. Result of pathogen inoculation assay on the transgenic plants showed that the transgenic plants had a higher resistant disease score of 1-2 grade than the control.