Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening.

Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 infection was investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosis and secreting inflammatory factors such as IL-1ß. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing infection time, and USA300 induces mPEOs to undergo pyroptosis and autophagy. In addition, we performed a drug screen for the mPEO infection model and showed that vancomycin restores cell viability and inhibits bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20-50 nm) and M40 (20-50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Accelerated complete human skin architecture restoration after wounding by nanogenerator-driven electrostimulation.

BACKGROUND: Electrostimulation (ES) therapy for wound healing is limited in clinical use due to barriers such as cumbersome equipment and intermittent delivery of therapy. METHODS: We adapted a human skin xenograft model that can be used to directly examine the nanogenerator-driven ES (NG-ES) effects on human skin in vivo-an essential translational step toward clinical application of the NG-ES technique for wound healing. RESULTS: We show that NG-ES leads to rapid wound closure with complete restoration of normal skin architecture within 7 days compared to more than 30 days in the literature. NG-ES accelerates the inflammatory phase of wound healing with more rapid resolution of neutrophils and macrophages and enhances wound bed perfusion with more robust neovascularization. CONCLUSION: Our results support the translational evaluation and optimization of the NG-ES technology to deliver convenient, efficient wound healing therapy for use in human wounds.

A self-powered implantable and bioresorbable electrostimulation device for biofeedback bone fracture healing.

Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have been largely limited by the complexity of equipment operation and stimulation implementation. Here, we present a self-powered implantable and bioresorbable bone fracture electrostimulation device, which consists of a triboelectric nanogenerator for electricity generation and a pair of dressing electrodes for applying electrostimulations directly toward the fracture. The device can be attached to irregular tissue surfaces and provide biphasic electric pulses in response to nearby body movements. We demonstrated the operation of this device on rats and achieved effective bone fracture healing in as short as 6 wk versus the controls for more than 10 wk to reach the same healing result. The optimized electrical field could activate relevant growth factors to regulate bone microenvironment for promoting bone formation and bone remodeling to accelerate bone regeneration and maturation, with statistically significant 27% and 83% improvement over the control groups in mineral density and flexural strength, respectively. This work provided an effective implantable fracture therapy device that is self-responsive, battery free, and requires no surgical removal after fulfilling the biomedical intervention.

Wearable and Implantable Electroceuticals for Therapeutic Electrostimulations.

Wearable and implantable electroceuticals (WIEs) for therapeutic electrostimulation (ES) have become indispensable medical devices in modern healthcare. In addition to functionality, device miniaturization, conformability, biocompatibility, and/or biodegradability are the main engineering targets for the development and clinical translation of WIEs. Recent innovations are mainly focused on wearable/implantable power sources, advanced conformable electrodes, and efficient ES on targeted organs and tissues. Herein, nanogenerators as a hotspot wearable/implantable energy-harvesting technique suitable for powering WIEs are reviewed. Then, electrodes for comfortable attachment and efficient delivery of electrical signals to targeted tissue/organ are introduced and compared. A few promising application directions of ES are discussed, including heart stimulation, nerve modulation, skin regeneration, muscle activation, and assistance to other therapeutic modalities.

[Evaluation of taste changes of Scutellariae Radix before and after wine-frying based on electronic ongue technology and its application in identification of Scutellariae Radix pieces].

Scutellariae Radix(Huangqin) is a well-known traditional Chinese medicine(TCM) used for the treatment of clearing heat in clinical application. It is bitter-cold by using directly, but the bitter-cold property can be relieved after wine-frying. The study of taste changes before and after wine-frying of Scutellariae Radix is of great significance in identifying Scutellariae Radix and wine-processed Scutellariae Radix and clarifying the traditional theory of wine-processing. In this experiment, 10 batches of Scutellariae Radix and wine-processed Scutellariae Radix were prepared. The contents of 5 flavonoids were determined by high performance liquid chromatography(HPLC), and principal component analysis(PCA) was performed with 5 flavonoids as variables. As a result, the contents were different in different batches of Scutellariae Radix, but Scutellariae Radix and wine-processed Scutellariae Radix could not be distinguished. Five sensory attributes(sour, salty, fresh, sweet, and bitter) were evaluated by artificial tasting, and the response values of 7 sensors(AHS, AHS, PKS, CTS, NMS, CPS, ANS, SCS) representing the taste of pieces were detected by electronic tongue. The correlation between sensory evaluation and response values of the electronic tongue were analyzed, and the results showed that the sensory evaluation of sour, salty, fresh, sweet, bitter and AHS, CTS, NMS, ANS, SCS sensors had different degrees of correlation, indicating that the electronic tongue technology can be used as an alternative to artificial taste and can serve as a means for quantifying the taste, and it can be used to evaluate the taste of TCM pieces. The taste method was used to analyze the response values of the electronic tongue, and the results showed that the bitterness of wine-processed Scutellariae Radix decreased and the salty taste increased. PCA was used to analyze taste changes before and after wine-processed Scutellariae Radix, and the results showed that taste differences between 2 pieces were divided into 2 categories. PCA loading scattering plots showed that response of saltiness and bitterness were the major factors to affect overall taste in Scutellariae Radix and wine-processed Scutellariae Radix. Based on electronic tongue response values, the Fisher discriminant model for Scutellariae Radix and wine-processed Scutellariae Radix was established, which showed that it could effectively discriminate them with a recognition rate of 100%. The experimental results showed that the electronic tongue combined with multivariate statistical analysis can be used to evaluate taste of TCM, at the same time, it could provide a fast and simple method for identifying different processed products.

Respiration-driven triboelectric nanogenerators for biomedical applications.

As a fundamental and ubiquitous body motion, respiration offers a large amount of biomechanical energy with an average power up to the Watt level through movements of multiple muscles. The energy from respiration featured with excellent stability, accessibility and continuality inspires the design and engineering of biomechanical energy harvesting devices, such as triboelectric nanogenerators (TENGs), to realize human-powered electronics. This review article is thus dedicated to the emerging respiration-driven TENG technology, covering fundamentals, applications, and perspectives. Specifically, the human breathing mechanics are first introduced serving as the base for the developments of TENG devices with different configurations. Biomedical applications including electrical energy generation, healthcare monitoring, air filtration, gas sensing, electrostimulation, and powering implantable medical devices are then analyzed focusing on the design-application relationships. At last, current developments are summarized and critical challenges for driving these intriguing developments toward practical applications are discussed together with promising solutions.

Evaluation of taste changes of Scutellariae Radix before and after wine-frying based on electronic ongue technology and its application in identification of Scutellariae Radix pieces / 中国中药杂志

Scutellariae Radix(Huangqin) is a well-known traditional Chinese medicine(TCM) used for the treatment of clearing heat in clinical application. It is bitter-cold by using directly, but the bitter-cold property can be relieved after wine-frying. The study of taste changes before and after wine-frying of Scutellariae Radix is of great significance in identifying Scutellariae Radix and wine-processed Scutellariae Radix and clarifying the traditional theory of wine-processing. In this experiment, 10 batches of Scutellariae Radix and wine-processed Scutellariae Radix were prepared. The contents of 5 flavonoids were determined by high performance liquid chromatography(HPLC), and principal component analysis(PCA) was performed with 5 flavonoids as variables. As a result, the contents were different in different batches of Scutellariae Radix, but Scutellariae Radix and wine-processed Scutellariae Radix could not be distinguished. Five sensory attributes(sour, salty, fresh, sweet, and bitter) were evaluated by artificial tasting, and the response values of 7 sensors(AHS, AHS, PKS, CTS, NMS, CPS, ANS, SCS) representing the taste of pieces were detected by electronic tongue. The correlation between sensory evaluation and response values of the electronic tongue were analyzed, and the results showed that the sensory evaluation of sour, salty, fresh, sweet, bitter and AHS, CTS, NMS, ANS, SCS sensors had different degrees of correlation, indicating that the electronic tongue technology can be used as an alternative to artificial taste and can serve as a means for quantifying the taste, and it can be used to evaluate the taste of TCM pieces. The taste method was used to analyze the response values of the electronic tongue, and the results showed that the bitterness of wine-processed Scutellariae Radix decreased and the salty taste increased. PCA was used to analyze taste changes before and after wine-processed Scutellariae Radix, and the results showed that taste differences between 2 pieces were divided into 2 categories. PCA loading scattering plots showed that response of saltiness and bitterness were the major factors to affect overall taste in Scutellariae Radix and wine-processed Scutellariae Radix. Based on electronic tongue response values, the Fisher discriminant model for Scutellariae Radix and wine-processed Scutellariae Radix was established, which showed that it could effectively discriminate them with a recognition rate of 100%. The experimental results showed that the electronic tongue combined with multivariate statistical analysis can be used to evaluate taste of TCM, at the same time, it could provide a fast and simple method for identifying different processed products.

Mechanism of Tripterygium hypoglaucum Radix-Leonurus japonicus Herba for Treating Rheumatoid Arthritis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:Computer network pharmacology technology was used to screen the main active ingredients of Tripterygium hypoglaucum radix-Leonurus japonicus herba for the treatment of rheumatoid arthritis(RA), predict the targets of the active ingredients, establish a pharmaceutical ingredient-active ingredient-target network, and further explore the potential mechanism of Tripterygium hypoglaucum radix-Leonurus japonicus herba for the treatment of RA. Method:RA disease targets were collected through DisGeNET, TTD, and Drugbank databases, the potential active components of Tripterygium hypoglaucum radix and Leonurus japonicus herba and their corresponding targets were obtained from the Chinese Medicine System Pharmacology Analysis Platform (TCMSP); common targets for drugs and diseases were screened by using the ImageGP platform; a common target interaction (PPI) network model was constructed by using the String database, a "drug-active ingredient-key target" network was constructed by using Cytoscape software, a protein interaction network was constructed by using the String database, gene function (GO) analysis and pathway enrichment analysis based on the Kyoto Gene and Genomic Encyclopedia (KEGG) were performed by using the ClueGO plug-in. Result:Through screening, 9 active pharmaceutical ingredients were obtained, involving a total of 235 targets, and 7 active ingredients were related to the disease targets. 24 common targets for Tripterygium hypoglaucum radix Leonurus japonicus herba-disease were obtained. The common targets were mainly enriched in 278 biological processes and 141 signaling pathways to play a role in the treatment of RA. Conclusion:The therapeutic effect of Tripterygium hypoglaucum radix Leonurus japonicus herba on RA reflects the characteristics of multi-component-multi-target-multi-channel of traditional Chinese medicine, and provides a scientific basis for explaining its mechanism and clinical application of RA.

Mechanism of Wulingsan in Treatment of Rheumatoid Arthritis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To study the mechanism of Wulingsan (WLS) in the treatment of rheumatoid arthritis (RA) by network pharmacology. Method:The active components of WLS were screened on traditional Chinese medicine systems pharmacology(TCMSP) platform, and the targets were predicted in DragBank database. The "component-target" network was constructed by Cytoscape 3.2.1 software. Disease targets were searched in TTD, DrugBank and DisGenet databases. The Venn diagram was built to extract the target of WLS in the treatment of RA, and the gene oesthetics(GO) function annotation and Kyoto Encyclopedin of Genes and Genomes(KEGG) signal pathway enrichment analysis were performed by cluego plugin. The TCM-component-target-pathway network of WLS was constructed, and the network feature analysis was made by Network Analyzer. Result:Totally 52 components and 297 potential targets in WLS and 1 845 targets relating to RA were excavated, and 49 common targets of WLS-RA were obtained. The common targets were mainly enriched in 322 biological processes and 31 signaling pathways. Conclusion:WLS may regulate targets, such as prostaglandin epoxide synthase 2 (PTGS2), transforming growth factor-β1 (TGF-β1), cysteine aspartate protein-3 (Caspase-3), transcription factor p65 (RELA), progesterone receptor (PGR), and adjust cancer-related pathways, tumor necrosis factor(TNF) signaling pathways, interleukin-17(IL-17) signaling pathways, nuclear factor-κB(NF-κB) signaling pathways, Th17 cell differentiation, so as to inhibit the inflammatory response, regulate immune function and adjust apoptosis to treat rheumatoid arthritis.

Mechanism of Duanteng Yimutang in Treating Rheumatoid Arthritis Based on Network Pharmacology Approach / 中国实验方剂学杂志

Objective:Duanteng Yimutang(DTYMT) has a significant effect in treating rheumatoid arthritis, but its composition is complex and its mechanism is not clear. It is worthwhile to use network pharmacology approach to find active components, therapeutic targets and signal pathways of DTYMT. Method:The drug composition was selected according to the pharmacokinetic parameters in the pharmacology database, the analysis platform (TCMSP) and the TCM integrated database (TCMID) of the Traditional Chinese Medicine System. The drug and disease targets were excavated in the Drugbank database and the Therapeutic Target Database (TTD), and the drug-target-pathway network was constructed by network pharmacology tool Cytoscap, in order to explore the mechanism of the action of the components in the DTYMT. Result:It was found that 11 effective components of DTYMT could target 42 proteins in rheumatoid arthritis, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), cyclooxygenase-2 (COX2), matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3), and inducible nitric oxide synthase (NOS2). Various pathways, including tumor necrosis factor (TNF) signaling pathway, interleukin-17 (IL-17) pathway, helper T cell 17 (Th17) differentiation pathway, rheumatic arthritis pathway, nuclear factor κB (NF-κB) pathway, osteoclast differentiation pathway, and ovarian steroid production pathway, were involved. Conclusion:DTYMT may be used to regulate inflammatory cytokines mainly through multiple inflammatory-related signal pathways, so as to play anti-inflammatory and immunoregulatory roles in the treatment of rheumatoid arthritis.

Detecting violation in abstract pitch patterns with mismatch negativity.

The human brain automatically extracts regularities embedded in environmental auditory events. This study investigated the extraction of abstract patterns by measuring mismatch negativity (MMN). Participants watched a silent subtitled movie and ignored a sequence of auditory events comprising frequent standards and rare deviants presented in the background. Tone triplets with varying pitch (first-order property) served as the auditory events. The pitch intervals (interval 1 and interval 2) between the tones in a triplet and the ratio of interval 1 and 2 were considered second- and third-order properties, respectively. Both second- and third-order properties of the standards were kept constant in the mixed patterns block, while only the third-order property was kept constant in the ratio pattern block. Four sets of tone triplets violating the interval and ratio patterns with different deviance levels were presented as deviants in both blocks, and subtracted with physically identical stimuli in a control block to isolate the MMNs. Interval and ratio pattern deviants elicited MMNs in the mixed patterns block while only ratio pattern deviants elicited MMNs in the ratio pattern block. Larger MMNs were elicited by large deviants as compared to small deviants. These results suggest that the change detection system is sensitive to the violation of both second- and third-order abstract patterns. In addition to regularities in the abstract properties of auditory events, regularities in the relationships between abstract properties can also be extracted. This ability plays an important role in music and language perception.

YY1-C/EBPα-miR34a regulatory circuitry is involved in renal cell carcinoma progression.

Renal cell carcinoma (RCC) is a common urological malignancy. It remains unclear, however, whether Yin Yang 1 (YY1) plays a functional role in the development of human RCC. In the present study, we demonstrated that levels of YY1 were significantly increased in primary RCC tissues when compared to these levels in the matched healthy tissues. YY1 knockdown inhibited cell growth, migration and invasion of RCC cells. Additionally, we highlighted a positive feedback-loop pathway resulting in YY1 upregulation. We observed that overexpression of YY1 caused repression of C/EBPα and the inhibition of C/EBPα led to the suppression of miR-34a. Since YY1 is a direct target of miR-34a, the low level of miR-34a increased the expression of YY1, promoting the aggressiveness of RCC cells. Furthermore, this feedforward mechanism was found in RCC tissues. We observed that miR-34a was downregulated in the pools of cancer tissues when compared to that of the normal tissues. The expression of miR-34a displayed an inverse correlation with YY1, but a positive correlation with C/EBPα. In conclusion, our study highlights the importance of a novel regulatory circuitry for YY1 activation in maintaining the aggressive phenotypes of RCC.

Wuziyanzong compound relieves oxidative stress injury and inhibits the apoptosis of Sertoli cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Wuziyanzong Compound on oxidative stress injury and the apoptosis of Sertoli cells.</p><p><b>METHODS</b>We added H2O2 (100 mmol/L) and Wuziyanzong extract to the culture solution of TM4 cells, which were divided into a control, a model and three Wuziyanzong groups (low dose: 0.2 mg/ml, medium dose: 1 mg/ml, and high dose: 5 mg/ml). After 24 hours of intervention, we detected the absorbance value by MTT assay, measured the SOD activity and MDA content using the xanthine oxidase and thiobarbituric acid method respectively, and determined the apoptosis and survival rate of the cells by flow cytometry and the expression of caspase-3 mRNA by real time PCR.</p><p><b>RESULTS</b>After treated with low-, medium- and high-dose Wuziyanzong Compound, the absorbance value of the TM4 cells was increased from 0.23 +/- 0.01 in the model group to 0.27 +/- 0.02, 0.30 +/- 0.01 and 0.35 +/- 0.01, the SOD activity increased from (8.32 +/- 0.62) U/ml to (9.69 +/- 0.59), (10.47 +/- 0.74) and (12.28 +/- 0.38) U/ ml, the MDA content decreased from (6.99 +/- 0.74) mol/L to (5.78 +/- 0.28), (4.19 +/- 0.43) and (3.42 +/- 0.51) mol/L, the cell apoptosis rate decreased from (21.63 +/- 1.38)% to (17.87 +/- 0.75), (14.10 +/- 0.50) and (9.53 +/- 1.34)%, the cell survival rate increased from (65.67 +/- 7.48)% to (70.37 +/- 1.12), (72.57 +/- 1.95) and (81.60 +/- 2.46)%, and the relative expression of caspase-3 mRNA decreased from 2.69 +/- 0.16 to 2.47 +/- 0.12, 2.38 +/- 0.16 and 1.96 +/- 0.11, respectively.</p><p><b>CONCLUSION</b>Wuziyanzong Compound can relieve oxidative stress injury and inhibit the apoptosis of TM4 cells.</p>

Ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys induced transdifferentiation of BMSCs in mice: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe and evaluate the effect of transdifferentiation of bone marrow derived stroma cells (BMSCs) into nerve cells by ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys.</p><p><b>METHODS</b>The BMSCs in vitro cultured after treated by ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys were divided into 5 groups, i.e., the blank group, the low dose group (6 g/L mixture), the high dose group (12 g/L mixture), the combination group (3 g/L mixture + 0.5 mmol/Lbeta-mercaptoethanol), and the positive control group (13-mercaptoethanol). The effects of transdifferentiation of nerve cells were observed using toluidine blue staining in each group. The differences of 5 specific neuroproteins, i.e. neuron-specific enolase (NSE), nestin, neurofilament protein (NFP), microtubule associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP) were detected using immunohistochemical technique and immunofluorescent technique respectively. The changes of the cell cycle were detected using flow cytometry (FCM).</p><p><b>RESULTS</b>After induction BMSCs changed morphologically. The morphological features were weaker in the high and low dose groups than in the combination group and the positive group. Except the blank group, the aforesaid 5 proteins expressed positively in the rest groups. Their expression levels were highest in the positive control group (P <0.05), followed by the combination group (P <0.05). As for the cell proliferation rate detected by FCM, it was the lowest in the positive control group, followed by high dose group, low dose group, and then the combination group (all P <0.05).</p><p><b>CONCLUSIONS</b>The ultrafiltration membrane extract mixture from Angelica sinensis and Hedysarum polybotrys could effectively induce the transdifferentiation of BMSCs into nerve cells. Its inducing capacities were weaker in the positive control group, but it showed marked proliferation effects on differentiated cells. Therefore, the mixture might be a more ideal medication pathway for effectively inducing BMSCs' transdifferentiation into nerve cells, which might have higher proliferation and be used for clinical research.</p>

Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid.

Ulcerative colitis involves complicated etiology and presents diverse symptoms including intestine inflammation, bowel pain and diarrhea. Anti-inflammatory drugs are the mainstay in patient care, accompanied with antidiarrhea and analgesic agents used as symptomatic treatment. A classic traditional Chinese medicine formula, Fructus Mume pill (FMP), showed remarkable therapeutic efficacy in treating ulcerative colitis. However, since it contains many herbs and countless chemicals, the underlying mechanism is not clear. In this study, we selected three alkaloids from FMP, namely, berberine, hypaconitine and skimmianine to study the individual drug effect and compare these results with the BHS combination on: 1) The recovery of ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. 2) Mice with xylene-induced acute exudative edema and acetic acid-induced writhing. 3) Gastrointestinal transit inhibition, and 4) the response of HT29 cells after treatment with lipopolysaccharide. We found that the compound hypaconitine showed a potent analgesic effect, while skimmianine acted as an antidiarrhea agent and the component berberine was the key agent exerting anti-inflammatory effect. However, since berberine killed the commensal bacteria and induced lipopolysaccharide release, it could at the same time aggravate colon inflammation. The three-alkaloid combination BHS produced complementary and synergistic effects in colon inflammation recovery, relieving acetic acid-induced bowel pain and xylene-induced acute exudative edema. BHS also decreased lipopolysaccharide production and enhanced the therapeutic efficacy. It is hoped that this study will lay the foundation to further dissect and understand the FMP formula to improve the treatment with simplified and well defined drug combinations for this dreadful disease.

Chemical constituents from Solanum lyratum Thunb / 军事医学科学院院刊

Objective To investigate the chemical constituents of the 60% alcohol extract of Solanum lyratum Thunb..Method The compounds were isolated by column chromatography over silica gel and Sephadex LH-20 and preparative TLC.Their structures were elucidated on the basis of physicochemical property and spectral data.Resulut Eleven compounds were isolated and identified as:ononin(1), genistin(2), 5-hydroxyl ononin(3), formononetin(4), daidzein(5), daidzin(6), 4-hydroxy-benzaldehyde(7),vanillic acid(8), protocatechuic acid(9),ethyl-α-D-arabinofuranoside(10) and ursolic acid(11).Conclusion Compounds 1,2,3,10 and 11 are isolated from S.lyratum for the first time.

Immunomodulation of Rheum tanguticum polysaccharide (RTP) on the immunosuppressive effects of dexamethasone (DEX) on the treatment of colitis in rats induced by 2,4,6-trinitrobenzene sulfonic acid.

Dexamethasone (DEX) is still the main choice for colitis, although the immunosuppressive side effects are still the troublesome problems to overcome. In our previous study, Rheum tanguticum polysaccharide (RTP), extracted from traditional Chinese medicine rhubarb, targeted mannose receptor, showed immunoregulatory effect on the balance of Th1 and Th2 polarization in colitis rats. For the present study, we hypothesized that RTP could regulate the immunosuppressive effects of DEX. Taking advantage of the colon delivery ability of the polysaccharide, we prepared the double emulsion of RTP microsphere containing DEX to investigate the potential immunoregulatory effects of RTP on DEX immunosuppression in TNBS-induced colitis in rats. As expected, DEX-RTP microsphere showed not only significant immunomodulatory effects, but also strong anti-inflammation. The microsphere balanced enteric bacteria disorder, decreased TLR4 activation and promoted the balance of Th1 and Th2 polarization, inhibited NF-kappaB activity. Especially, DEX-RTP showed significant colon injury reparation. DEX alone exhibited a strong anti-inflammatory effect by suppressing MPO activity, down-regulate NF-kappaB activity and Th1 cytokines production. However, DEX showed severe immunosuppressive effects. It aggravated the intestinal commensal bacteria disorder, induced thymus atrophy and the further imbalance of Th1/Th1 cytokine polarization. RTP showed significant immunoregulatory effects. A significant protection on the intestinal bacterial balance, TLR4 and NF-kappaB activation decreased, and Th1/Th2 cytokine production balance were showed in RTP. In conclusion, DEX-RTP microsphere delivered DEX directly to the colon avoiding the absorption at the upper intestinal tract and showed synergistic effects on colitis both from the strong anti-inflammatory effects of DEX and from the immunoregulation of RTP.

The possible mechanisms of Fructus Mume pill in the treatment of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Mume pill (FMP) has been used as a folk remedy for gastrointestinal diseases in China over thousands of years. FMP was approved for the treatment of gastrointestinal diseases in 2001 by the State Food and Drug Administration (SFDA) of China. Although FMP had significant efficacy for treatment of the patients with inflammatory bowel disease (IBD) in the clinic, the mechanism of action is still unclear. AIM OF THE STUDY: In the present study, the effects and possible mechanism of FMP on colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) were investigated. MATERIALS AND METHODS: Fifty-four SD rats were divided into six groups. Nine rats for each group from three independent experiments were investigated for the effects of FMP. RESULTS: FMP protected against diarrhea, colon weight increase, colonic accretion, ulceration and myeloperoxidase (MPO) activity elevation. The effects of FMP on recovery of colonic damage and restoration of the normal structures of colorectums were superior to dexamethasone (DEX). FMP promoted the restoration of abnormal cytokine secretion after TNBS treatment. FMP was effective in restoring the balance of intestinal bacteria population from the imbalance of G(+)/G(-) in rats with colitis. CONCLUSIONS: The results indicated that FMP is effective in treatment of colitis in an experimental rat model. The possible mechanisms may be through down-regulation of Th1-polarized immune response and opsonic effect of intestinal commensal bacteria in this model system.

[Atomic absorption fingerprint and identification studies of Da Huo Luo pill. I. Exploration of inorganic elements fingerprint for establishment of industrial standard].

The fingerprints for most of Chinese medicines based on their organic compositions have been well established. Nevertheless, there are very few known fingerprints which are based on inorganic elements. In order to identify the Da Huo Luo Dan and its efficiency from other Chinese medicines, the authors attempted to set up a fingerprint which could be determined by the measurement of inorganic elements in Da Huo Luo Dan and other Chinese medicines. In the present study, the authors first employed 28 batches of Da Huo Luo Dan produced by Zhang-Shu Pharmatheutical Company in Jiang Xi Province to screen 12 kinds of inorganic elements measured by atomic absorption spectrophotometer and established the atomic absorption fingerprints. Secondly, the authors tried to identify Da Huo Luo Dan and other Chinese medicines by using the similarly analysis of vectors and the statistical analysis of compositional data. The result showed that the methods the authors used here were predictable to tell the efficiency of Da Huo Luo Dan from others. The authors' study also proves that establishment of standard for quality control by analysis of inorganic elements in Chinese medicines is feasible. The present study provides a new idea and a new technique that serve for the establishment of industrial standards for analysis of inorganic elements fingerprint to explore the effects of Chinese medicines.