Preparation and characterization of biomimetic liposomes coated with erythrocyte membrane co-loading triptolide and celastrol / 药学学报

Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.

Mechanisms and application of triptolide against breast cancer / 中国中药杂志

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people'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.

Diverse Roles of Inhibitor of Differentiation in Immune Cell Development and Hematologic Malignancies / 中国生物化学与分子生物学报

Inhibitor of differentiation (Id) is a member of the helix-loop-helix protein family and exerts negative transcriptional regulation by forming heterodimers with other HLH proteins to inhibit gene expression. Id can promote cell proliferation and inhibit cell differentiation. Especially, Id plays an essential role in the development and differentiation of various immune cells. This review mainly introduces the latest research progress in how members of the Id family regulate the generation and fate determination of multiple cell lineages in the innate and adaptive immune systems. By interacting with different transcription factors such as E protein, Id has a variety of functions in the differentiation process of natural killer cells, innate lymphoid cells, T cells, and B cells, etc., ensuring the well-coordinated development of immune cells in various immune organs. On the other hand, the abnormal expression and functional deficiency of the Id gene are closely related to the occurrence and progression of hematologic malignancies. In different hematologic malignancies ranging from leukemia to malignant lymphoma, Id plays diverse roles as a cancer-promoting or tumor suppressor factor. Therefore, Id can be used as a marker for the diagnosis and prognosis of hematologic malignancies and has the potential to become an important target for cancer therapy.

Preparation of Periplaneta americana Thermosensitive Hydrogel and Investigation of Its Wound Healing Effect on Diabetic Rats / 中国实验方剂学杂志

Objective:To prepare Periplaneta americana thermosensitive hydrogel and investigate its effect on wound healing in diabetic rats. Method:Taking N-isopropylacrylamide (NIPAM) and acrylic acid (AAc) as monomers, thermosensitive poly(NIPAM-co-AAc) [P(NIPAM-co-AAc)] polymeric material was prepared by free radical polymerization, then thermoresponsive copolymer P(NIPAM-co-AAc)-g-HA was synthesized by conjugating P(NIPAM-co-AAc) to hyaluronic acid (HA). The structure and lower critical solution temperature (LCST) of the graft copolymer were characterized by proton nuclear magnetic resonance spectroscopy (1H-NMR) and ultraviolet spectrophotometry (UV). P. americana thermosensitive hydrogel was prepared by dialysis method, and it was characterized by scanning electron microscope (SEM), rotation rheometer and thermogravimetric analyzer to observe section structure, rheological properties and thermal stability. Differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy were employed to identify the inclusion of P(NIPAM-co-AAc)-g-HA temperature sensitive material for P. americana extract, and to investigate the effect of P. americana thermosensitive hydrogel on wound healing in diabetic rats, and the rate of wound healing was calculated by Image-Pro Plus 6.0 software. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes of the wounds of rats in each group. Result:P(NIPAM-co-AAc)-g-HA temperature sensitive material was successfully synthesized, its LCST was between 29 ℃ and 31 ℃, it had a dense and uniform porous structure and could uniformly include P. americana extract. Pharmacodynamic studies showed that P. americana thermosensitive hydrogel group had the best effect on promoting wound healing, its infiltration degree of inflammatory cells was significantly reduced, collagen and fibroblasts arranged neatly and compactly, and the density of neovascularization was significantly increased by comparing with the model group. Conclusion:P. americana thermosensitive hydrogel can effectively promote wound healing of diabetic rats and overcome the shortage of marketed P. americana liquid preparations, this paper can provide a reference for the development of P. americana extract preparations to promote wound healing in diabetic patients.

Research progress of photothermal therapy combined with chemotherapy based on nano co-delivery strategy / 药学学报

In recent years, multi-modal combined anti-tumor has become an effective strategy for clinical tumor treatment. Photothermal therapy with its characteristics of minimally invasive, controllable, high efficiency, and strong specificity, can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. The research shows that the combination of photothermal therapy and chemotherapy has better synergistic antitumor effect. However, chemotherapeutic drugs and photothermal agents may have different pharmacokinetic behaviors in vivo, so it is difficult to ensure their effective transmission in tumor site, and the free form is easy to be metabolized and degraded in vivo. How to deliver the two therapeutic modes of drugs / photothermal reagents to tumor tissues in a specific, efficient and synchronous manner to achieve the best combined antitumor effect is an important problem to be solved in the combined antitumor application. The development of nano-drug delivery technology provides a new idea for the application of tumor treatment. In this paper, combined with the latest research progress in this field, the anti-tumor mechanism of photothermal therapy combined with chemotherapy, the advantages of nano drug delivery, the types and characteristics of commonly used nano materials and the principle of drug delivery are reviewed in order to provide a reference for the further development of multi-mode combined treatment of tumor.

Prescription compatibility connotation and action mechanism of Siwu Decoction in treating primary dysmenorrhea / 中国中药杂志

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.

Pharmacodynamics of Siwu Decoction on blood supply based on factor analysis / 中国中药杂志

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( P<0. 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.

Research progress on triptolide functionalized nanoparticulate drug delivery systems for tumor treatment / 中国中药杂志

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.

Research progress on anti-tumor effects and mechanisms of triptolide and its combined application / 中国中药杂志

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.

Network pharmacology-based study on mechanism of Siwu Decoction in treatment of primary dysmenorrhea / 中国中药杂志

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.

Antitumor status analysis on the co-delivery systems regarding the active ingredients of Chinese herbs combined with chemotherapeutic drugs / 药学学报

Anti-tumor intervention using a combination of drugs shows unique advantages in research and clinical practice. Active ingredients of Chinese herbal medicines can offer many advantages, such as high efficiency, low toxicity, wide effect and multiple targets. At present, the combination active ingredients of Chinese herbal and chemotherapy drugs have attracted increased attention. Nano-drug delivery system provides a good carrier platform for anti-tumor drugs. Nano-carrier-mediated drug combination is a promising strategy. In this paper, we review the mechanisms of the anti-tumor effects of active ingredients of traditional Chinese medicine combined with chemotherapeutic drugs and consider the advantages of drug-loaded nanoparticles, the types and characteristics of carriers. The aim is to provide a reference for the research of effective regimen for anti-tumor therapy.

Dissolution behavior of Fuzi Lizhong pill based on simultaneous determination of two components in Glycyrrhizae Radix et Rhizoma / 中国中药杂志

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for dissolution behavior by determining the dissolution rate of liquiritin and glycyrrhizic acid. High-performance liquid chromatography (HPLC) method for simultaneous content determination of the two active ingredients of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was established; The dissolution amount of these two active ingredients in fifteen batches of Fuzi Lizhong pill from five manufacturers was obtained at different time points, and then the cumulative dissolution rate was calculated and cumulative dissolution curve was drawn. The similarity of cumulative dissolution curve of different batches was evaluated based on the same factory, and the similarity of cumulative dissolution curve of different factories was evaluated based on the same active ingredients. The dissolution model of Fuzi Lizhong pill based on two kinds of active ingredients was established by fitting with the dissolution data. The best dissolution medium was 0.25% sodium lauryl sulfate. The dissolution behavior of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was basically the same and sustained release in 48 h. Three batches of the factories (factory 2, factory 3, factory 4 and factory 5) appeared to be similar in dissolution behavior, indicating similarity in dissolution behavior in most factories. Two of the three batches from factory 1 appeared to be not similar in dissolution behavior of liquiritin and glycyrrhizic acid. The dissolution data of the effective ingredients from different factories were same in fitting, and Weibull model was the best model in these batches. Fuzi Lizhong pill in 15 batches from 5 factories showed sustained release in 48 h, proving obviously slow releasing characteristics "pill is lenitive and keeps a long-time efficacy". The generally good dissolution behavior also suggested that quality of different batches from most factories was stable. The dissolution behavior of liquiritin and glycyrrhizic acid in different factories was different, suggesting that the source of medicinal materials and preparation technology parameters in five factories were different.

Analysis on dosage form theory and current application situation of traditional Chinese medicine pill / 中国中药杂志

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.

Serum amyloid A promotes the inflammatory response via p38-MAPK/SR-BI pathway in THP-1 macrophages / 生理学报

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 (P < 0.05). 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 (P < 0.05). 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) (P < 0.05). 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.

Protective effect of musk extract on rat's cerebral cortical neurons with inflammatory injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of musk extract (ME) and its possible mechanism on rat's cerebral cortical neurons with inflammatory injury induced by lipopolysaccharide (LPS).</p><p><b>METHODS</b>Neurons and astrocytes from newborn rat cerebral cortex were cultured in vitro respectively, and the astrocyte conditioned medium (ACM), obtained by treating astrocytes with 10 mg/L LPS and different concentrations of ME for 24 h, was added in the culture fluid of neurons. The survival rate and apoptotic rate of neurons were measured by MTT method and AO/EB stain; and the changes of inflammatory factors in the ACM were determined by ELISA.</p><p><b>RESULTS</b>The survival rate (%) of neurons treated by ACM with ME in concentrations of 18 mg/L, 36 mg/L, 72 mg/L and 144 mg/L was 52.55 +/- 3.52, 55.77 +/- 2.36, 64.89 +/- 3.45 and 73.67 +/- 1.80, respectively, significantly higher than that in the model neurons (43.62 +/- 4. 51, P < 0.05), while the apoptotic rate (%) in them, 68.11 +/- 2.16, 44.27 +/- 3.68, 32.56 +/- 2.14 and 21.89 +/- 2.46, respectively, was significantly lower than that in model neurons (71.33 +/- 3.25, P < 0.05 or P < 0.01). Level of IL-6 was decreasing along with the raising of ME concentration in the ACM, showing a concentration-dependent state.</p><p><b>CONCLUSION</b>ME shows apparent protective effect on neurons against inflammatory injury, especially in a high concentration (144 mg/L), which may be associated with the reduction of IL-6 secreted by astrocytes.</p>

Anatomic structural study of cerebellopontine angle via endoscope / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Minimally invasive surgery in skull base relying on searching for possible anatomic basis for endoscopic technology is controversial. The objective of this study was to observe the spatial relationships between main blood vessels and nerves in the cerebellopontine angle area and provide anatomic basis for lateral and posterior skull base minimally invasive surgery via endoscopic retrosigmoid keyhole approach.</p><p><b>METHODS</b>This study was conducted on thirty dried adult skulls to measure the spatial relationships among the surface bony marks of posterior cranial fossa, and to locate the most appropriate drilling area for retrosigmoid keyhole approach. In addition, we used 10 formaldehyde-fixed adult cadaver specimens for simulating endoscopic retrosigmoid approach to determine the visible scope.</p><p><b>RESULTS</b>The midpoint between the mastoid tip and the asterion was the best drilling point for retrosigmoid approach. A hole centered on this point with the 2.0 cm in diameter was suitable for exposing the related structures in the cerebellopontine angle. Retrosigmoid keyhole approach can decrease the pressure on the cerebellum and expose the related structures effectively which include facial nerve, vestibulocochlear nerve, trigeminal nerve, glossopharyngeal nerve, vagus nerve, accessory nerve, hypoglossal nerve, anterior inferior cerebellar artery, posterior inferior cerebellar artery and labyrinthine artery, etc.</p><p><b>CONCLUSIONS</b>Exact location on endoscope retrosigmoid approach can avoid dragging cerebellum during the minimally invasive surgery. The application of retrosigmoid keyhole approach will extend the application of endoscopic technology.</p>