Identification of Prognostic Markers of Glioblastoma through Bioinformatics Analysis.

Objective: Glioblastoma is the most common and aggressive type of the central nervous system cancers. Although radiotherapy and chemotherapy are used in the treatment of glioblastoma, survival rates remain unsatisfactory. This study aimed to explore differentially expressed genes (DEGs) based on the survival prognosis of patients with glioblastoma and to establish a model for classifying patients into different risk groups for overall survival. Methods: DEGs from 160 tumor samples from patients with glioblastoma and 5 nontumor samples from other patients in The Cancer Genome Atlas database were identified. Functional enrichment analysis and a protein-protein interaction network were used to analyze the DEGs. The prognostic DEGs were identified by univariate Cox regression analysis. We split patient data from The Cancer Genome Atlas database into a high-risk group and a low-risk group as the training data set. Least absolute shrinkage and selection operator and multiple Cox regression were used to construct a prognostic risk model, which was validated in a test data set from The Cancer Genome Atlas database and was analyzed using external data sets from the Chinese Glioma Genome Atlas database and the GSE74187 and GSE83300 data sets. Furthermore, we constructed and validated a nomogram to predict survival of patients with glioblastoma. Results: A total of 3572 prognostic DEGs were identified. Functional analysis indicated that these DEGs were mainly involved in the cell cycle and focal adhesion. Least absolute shrinkage and selection operator regression identified 3 prognostic DEGs (EFEMP2, PTPRN, and POM121L9P), and we constructed a prognostic risk model. The receiver operating characteristic curve analysis showed that the areas under the curve were 0.83 for the training data set and 0.756 for the test data set. The predictive performance of the prognostic risk model was validated in the 3 external data sets. The nomogram showed that the prognostic risk model was reliable and that the accuracy of predicting survival in each patient was high. Conclusion: The prognostic risk model can effectively classify patients with glioblastoma into high-risk and low-risk groups in terms of overall survival rate, which may help select high-risk patients with glioblastoma for more intensive treatment.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

[Species identification of Ligustrum lucidum].

Ligustrum lucidum is a woody perennial plant of genus Ligustrum in family Oleaceae. Its dried fruit has high medicinal value. In this study, the authors evaluated the variability and species identification efficiency of three specific DAN barcodes(rbcL-accD, ycf1a, ycf1b) and four general DAN barcodes(matK, rbcL, trnH-psbA, ITS2) for a rapid and accurate molecular identification of Ligustrum species. The results revealed that matK, rbcL, trnH-psbA, ITS2 and ycf1a were inefficient for identifying the Ligustrum species, and a large number of insertions and deletions were observed in rbcL-accD sequence, which was thus unsuitable for development as specific barcode. The ycf1b-2 barcode had DNA barcoding gap and high success rate of PCR amplification and DNA sequencing, which was the most suitable DNA barcode for L. lucidum identification and achieved an accurate result. In addition, to optimize the DNA extraction experiment, the authors extracted and analyzed the DNA of the exocarp, mesocarp, endocarp and seed of L. lucidum fruit. It was found that seed was the most effective part for DNA extraction, where DNAs of high concentration and quality were obtained, meeting the needs of species identification. In this study, the experimental method for DNA extraction of L. lucidum was optimized, and the seed was determined as the optimal part for DNA extraction and ycf1b-2 was the specific DNA barcode for L. lucidum identification. This study laid a foundation for the market regulation of L. lucidum.

[Synchronous evaluation of continuous dynamic dissolution and absorption of Compound Danshen Dropping Pills based on cellular bioelectrical effect].

The real-time cell-based assay(RTCA) was used to establish the bioelectrical sensing model of Compound Danshen Dripping Pills with rat cardiomyocytes(H9 c2). The time/dose-dependent cell response profiles(TCRPs) of in vitro dissolution and absorption of the pills were determined to establish the continuous dynamic dissolution and absorption kinetic models. Thereby, the cell index(CI)-based dissolution and absorption kinetic curves and kinetic models of Compound Danshen Dripping Pills were obtained. The optimal dissolution kinetic model was Weibull model. The similarity factors f_2 of dissolution curves were greater than 50 and the correlation coefficients of absorption curves were larger than 0.95. With the experiment about the efficacy on mice, percentages of the bleeding time of mice administrated with Compound Danshen Dripping Pills were calculated, and there was a correlation among dissolution, absorption, and efficacy curves(r > 0.9). RTCA is applicable to the study of the dissolution and absorption kinetics of solid compound Chinese medicine preparations. Thus, it is an innovative and feasible method to evaluate the quality and batch consistency of compound Chinese medicine preparations.

Simultaneous Evaluation of Dissolution and Absorption Study of Compound Danshen Tablets and Capsules Based on Cellular Electrical Sensing Model.

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations.

[Complete chloroplast genome of Ligustrum lucidum and highly variable marker identification for Ligustrum].

Ligustri Lucidi Fructus, the sun-dried mature fruit of Ligustrum lucidum, is cool, plain, sweet, and bitter, which can be used as both food and medicine, with the effects of improving vision, blacking hair, and tonifying liver and kidney. It takes effect slowly. However, little is known about the genetic information of the medicinal plant and it is still a challenge to distinguish Ligustrum species. In this study, the complete chloroplast genome of L. lucidum was obtained by genome skimming and then compared with that of five other Ligustrum species, which had been reported. This study aims to evaluate the interspecific variation of chloroplast genome within the genus and develop molecular markers for species identification of the genus. The result showed that the chloroplast genome of L. lucidum was 162 162 bp with a circular quadripartite structure of two single-copy regions separated by a pair of inverted repeats. The Ligustrum chloroplast genomes were conserved with small interspecific difference. Comparative analysis of six Ligustrum chloroplast genomes revealed three variable regions(rbcL-accD, ycf1a, and ycf1b), and ycf1a and ycf1b can be used as the species-specific DNA barcode for Ligustrum. Phylogeny analysis provided the best resolution of Ligustrum and supported that L. lucidum was sister to L. gracile. This study clarified the genetic diversity of L. lucidum from provenance, which can serve as a reference for further analysis of pharmacological differences and breeding of excellent varieties with stable drug effects.

Five-Flavor Sophora flavescens Enteric-Coated Capsules for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the incidence and prevalence of UC have been increasing consistently. Five-flavor Sophora falvescens enteric-coated capsule (FSEC), a licensed Chinese patent medicine, was specifically used to treat UC. This review was aimed to assess the effectiveness and safety of FSEC for the treatment of UC. METHODS: Six electronic databases were searched from inception to March 2021. Randomized clinical trials (RCTs) comparing FSEC or FSEC plus conventional Western medicine with conventional Western medicine in participants with UC were included. Two authors screened all references, assessed the risk of bias, and extracted data independently. Binary data were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and metric data as mean difference (MD) with 95% CI. The overall certainty of the evidence was assessed by GRADE. RESULTS: We included 15 RCTs (1194 participants, 763 in the FSEC group and 431 in the control group). The treatment duration ranged from 42 to 64 days. Twelve trials compared FSEC with conventional Western medicine, and two trials compared FSEC plus conventional medicine with conventional medicine. Another trial compared FSEC plus mesalazine with compound glutamine enteric capsules plus mesalazine. FSEC showed a higher clinical effective rate (improved clinical symptoms, colonoscopy results, and stools) (RR 1.12, 95% CI 1.05 to 1.20; 729 participants; 8 trials; low-quality evidence) as well as the effective rate of traditional Chinese medicine (TCM) syndromes (RR 1.10, 95% CI 1.01 to 1.20; 452 participants; 5 trials; low-quality evidence) compared to mesalazine. There was no significant difference in the adverse events between FSEC and control groups. CONCLUSIONS: FSEC may show effectiveness in UC treatment compared to conventional medicine, and the use of FSEC may not increase the risk of adverse events. Due to the limited number of clinical trials and low methodological quality of the included trials, our findings must be interpreted with discretion.

Complete chloroplast genome of Ligustrum lucidum and highly variable marker identification for Ligustrum / 中国中药杂志

Ligustri Lucidi Fructus, the sun-dried mature fruit of Ligustrum lucidum, is cool, plain, sweet, and bitter, which can be used as both food and medicine, with the effects of improving vision, blacking hair, and tonifying liver and kidney. It takes effect slowly. However, little is known about the genetic information of the medicinal plant and it is still a challenge to distinguish Ligustrum species. In this study, the complete chloroplast genome of L. lucidum was obtained by genome skimming and then compared with that of five other Ligustrum species, which had been reported. This study aims to evaluate the interspecific variation of chloroplast genome within the genus and develop molecular markers for species identification of the genus. The result showed that the chloroplast genome of L. lucidum was 162 162 bp with a circular quadripartite structure of two single-copy regions separated by a pair of inverted repeats. The Ligustrum chloroplast genomes were conserved with small interspecific difference. Comparative analysis of six Ligustrum chloroplast genomes revealed three variable regions(rbcL-accD, ycf1a, and ycf1b), and ycf1a and ycf1b can be used as the species-specific DNA barcode for Ligustrum. Phylogeny analysis provided the best resolution of Ligustrum and supported that L. lucidum was sister to L. gracile. This study clarified the genetic diversity of L. lucidum from provenance, which can serve as a reference for further analysis of pharmacological differences and breeding of excellent varieties with stable drug effects.

Chinese Patent Medicine as Adjuvant for Mild-to-Moderate Active Ulcerative Colitis: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese patent medicine for mild-to-moderate active ulcerative colitis (UC) using network meta-analysis (NMA). METHODS: We systematically searched PubMed, Cochrane library, Embase, Sino-Med, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journal Database (VIP) databases to October, 2020. We included randomized controlled trials (RCTs) on Chinese patent medicine for mild-to-moderate active UC. The main analysis was complemented by network subanalyses and standard pairwise comparisons. Statistical heterogeneity, inconsistencies, and ranking probability were also evaluated. RESULTS: The databases search identified 3222 citations, of which 33 RCTs involving 2971 patients met the inclusion criteria. A total of 15 Chinese patent medicines were analyzed. The overall quality of the included studies was low. Pairwise meta-analysis showed that Chinese patent medicine was superior to Mesalazine in improving disappearances of clinical symptoms, recurrence rate, and Mayo score. Based on decreases in adverse events, results from NMA showed that Xilei powder plus Mesalazine was more effective than other drugs. Other NMA results indicated that Danshen freeze-dried powder plus Mesalazine (RR: 0.13; 95% CI, 0.02-0.78) and Kangfuxin lotion plus Mesalazine (RR: 0.24; 95% CI, 0.07-0.57) were superior to Mesalazine in decreasing recurrence rate. Another NMA result indicated that Kangfuxin lotion plus Mesalazine (RR: 0.00; 95% CI, 0.00-0.02) and Zhi Kang capsule plus Mesalazine (RR: 0.00; 95% CI, 0.00-0.02) were superior to Mesalazine in increasing the disappearance of tenesmus. CONCLUSION: In the probability sorting, Xilei powder combined with Mesalazine ranked first for having the fewest adverse events, Maintaining Intestines Antidiarrheal Pills combined with Mesalazine ranked first for having the lowest recurrence rate, Xilei powder combined with Mesalazine ranked first for improving disappearance rate of mucopurulent bloody stool/abdominal pain, and Kangfuxin lotion combined with Mesalazine ranked first for improving the disappearance rate of diarrhea/tenesmus. However, there is a lack of direct comparisons among Chinese patent medicines for UC. More multiarm RCTs are needed in the future to provide direct comparative evidence.

Onion extract gel is not better than other topical treatments in scar management: A meta-analysis from randomised controlled trails.

To evaluate the efficacy and safety of onion extract (OE) gel on scar management, a systematic review was performed by searching Embase, PubMed, Medline, and the Cochrane Library databases, and a meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. Finally, 13 randomised controlled trails were enrolled for meta-analysis. OE gel increased the total improvement scores assessed by investigators (P < .00001) and patients (P < .00001) than no treatment, but no differences were detected between OE gel and other commonly used topical treatments assessed by investigators (P = .56) and patients (P = .39). Moreover, OE in silicone gel increased the total improvement scores assessed by investigators (P < .00001) and patients (P = .0007) than other treatments. OE gel increased the incidence of total adverse effects compared with no treatment (P < .0001) and other treatments (P = .008) by a fixed-effects model, and increased the incidence of dropping out caused by intolerance of treatments (P = .0002). OE gel not only has no superiority to commonly used topical treatments, but also has the potential to increase the incidence of adverse effects on scar management; OE in silicone gel might be the optimal topical choice for scar treatment; however, more evidences are needed to strength these conclusions.

[Comparison between charged aerosol detector and evaporative light scattering detector for analysis of sugar in Zhusheyong Yiqi Fumai and study on accuracy of methods].

Evaporative light scattering detector(ELSD) and charged aerosol detector(CAD) methods were established in this study for the content determination of four kinds of sugars in Zhusheyong Yiqi Fumai(YQFM), and the factors affecting the accuracy of CAD methods were discussed. HPLC-ELSD chromatographic separation was performed on a Shodex Asahipak NH2 P-50 column with acetonitrile-water(75∶25)as the mobile phase, with a flow rate of 0.8 mL·min~(-1), drift tube temperature of 80 ℃. The analysis by HPLC-CAD was performed on the same column with acetonitrile-water as mobile phase for gradient elution, with a flow rate of 0.8 mL·min~(-1), a neb temperature of 45 ℃, and power function(PF) of 1.3. The samples of YQFM were detected by ELSD and CAD respectively. It was found that YQFM was composed of fructose, glucose, sucrose and maltose. The linear relationship of the two methods was good, and the recoveries, reproducibility and stability of these four kinds of sugars measured by the two methods satisfied the requirements of methodology. Both CAD and ELSD detectors were accurate and reliable in detecting saccharides components in YQFM. In addition, it was revealed in this study for the first time that the PF parameter of CAD had an important influence on the accuracy of sugar determination and acted as the key parameter of CAD method. It was also found that for CAD, a non-linear detector, there was no significant difference between the results of linear regression and logarithmic regression.

Successive mineral nitrogen or phosphorus fertilization alone significantly altered bacterial community rather than bacterial biomass in plantation soil.

Bacteria play determining roles in forest soil environment and contribute to essential functions in the cycling of nitrogen (N) and phosphorus (P). Understanding the effects of different fertilizer applications, especially successive fertilization, on soil properties and bacterial community could reveal the impacts of fertilization on forest soil ecology and shed light on the nutrient cycling in forest system. This study aimed to evaluate the impacts of successive mineral N (NH4NO3) and P (NaH2PO4) fertilization at different rates, alone or together, on soil bacterial biomass and communities at 0-5, 5-10, and 10-20 cm. Compared with the control, N fertilization decreased soil pH, but P alone or with N fertilization had negligibly negative impacts on soil pH. Different mineral fertilizer applications, alone or together, showed no significant effects on soil organic matter contents, relative to the control treatment. Bacterial biomass remained stable to different fertilizations but decreased with sampling depths. Sole N or P fertilization, rather than combined fertilizations, significantly changed soil bacterial community structures. Our results demonstrated that mineral N or P fertilization alone significantly affected bacterial community structures rather than biomass in the plantation soils. KEY POINTS: • Impacts of successive mineral fertilization on soil bacteria were determined. • Mineral fertilization showed negligible impacts on bacterial biomass. • N additions stimulated Chloroflexi relative abundances. • Mineral N or P fertilization significantly altered bacterial community structure.

Influence of rainfall intensity and slope on suspended solids and phosphorus losses in runoff.

Suspended solids (SS) and phosphorus (P) losses in rainfall generated runoff can lead to the deterioration of surface water quality. Simulated rainfall experiments were conducted to investigate the effects of rainfall intensity (30, 50, 65, and 100 mm h-1) and land slope (0°, 5°, and 10°) on SS and P losses in runoff from experimental rigs containing bare land soil and soil planted with grass (tall fescue). In addition, total phosphorus (TP), particulate phosphorus (PP), and dissolved phosphorus (DP) losses in runoff were also measured. Results showed that tall fescue could reduce loads of SS by 86-99.5%, PP by 92-98.5%, and TP by 55-89.8% in runoff compared with losses from bare soil; this is due to a combination reduced raindrop kinetic energy at the soil surface, reduced soil erodibility in the presence of plant roots and shoots, and an increase in roughness and consequently reduced overland flow velocity resulting in the trapping of particles. Linear relationships between losses of SS and TP and between TP and PP in runoff were significant (R2 > 0.93) in both bare soil and grass. In addition, SS and TP losses increased greatly significantly with rainfall intensity and slope. The influence of rainfall intensity on SS and P losses was greater than the influence of slope. Simple linear regressions were constructed between losses of SS and P, the rainfall intensity (30 to 100 mm h-1), and land slope (0° to 10°). The multiple regression equations of SS and P losses in runoff established in this study can provide a simple predicting approach for estimating the non-point source pollution load of SS and P arising from rainfall.

Enhancement of phytochemical bioaccessibility from plant-based foods using excipient emulsions: impact of lipid type on carotenoid solubilization from spinach.

Effects of lipid type in excipient emulsions on the bioaccessibility of carotenoids (lutein and ß-carotene) in spinach were studied using a simulated gastrointestinal tract (GIT). Results showed that the lipid type only had a minor impact on the physical and structural characteristics of the spinach/emulsion mixtures as they passed through simulated mouth, stomach, and small intestine phases. However, a significant effect was observed on lipid digestion, mixed micelle formation, and carotenoid bioaccessibility. Excipient emulsions containing mainly medium chain triacylglycerols (MCTs) (MCT and coconut oils) had faster initial lipid digestion rates, higher overall digestibility, smaller mixed micelle sizes, and higher lutein bioaccessibilities than those containing mainly long chain triacylglycerols (LCTs) (corn, olive, and fish oils). Excipient emulsions rich in long chain monounsaturated fatty acids (MUFAs) (corn and olive oils) formed larger mixed micelles and gave higher ß-carotene bioaccessibilities than those rich in either medium chain saturated fatty acids (SFAs) (MCT and coconut oils) or long chain polyunsaturated fatty acids (PUFAs) (fish oil). These differences in bioaccessibility were attributed to differences in micelle size and solubilization capacity, as well as carotenoid dimensions. Finally, emulsions containing a mixed oil phase (MCT oil : corn oil = 1 : 1, w/w) appreciably increased both lutein (from 21% to 42%) and ß-carotene (from 6.8% to 25%) bioaccessibility from spinach compared to a control (no oil). These results suggest that mixed LCT-MCT oil phases may be useful for the design of excipient emulsions for improving the bioaccessibility of various hydrophobic nutraceuticals.

Molecular identification and functional analysis of Ctrp9 in Epinephelus coioides.

CTRP9 is a member of the C1q/TNF-related protein (CTRP) superfamily and has been studied in mammals, whereas the comparative studies of CTRP9 in non-mammalian species are still absent. In this study, ctrp9 was isolated and characterized from the orange-spotted grouper (Epinephelus coioides). The full-length cDNA of ctrp9 was 1378 bp in size with an ORF (open reading frame) of 1020 bp that encodes a 339 amino acid pre-pro hormone. The mRNA expression of ctrp9 showed a rather high level in the kidney and brain, but a low level in other tissues. Furthermore, the mRNA expression of ctrp9 decreased significantly in the liver after fasting for 7 days and restored to the normal levels after refeeding. In contrast, the ctrp9 mRNA level increased in the hypothalamus after fasting. The recombinant gCtrp9 (globular Ctrp9) was prepared using the Pichia pastoris expression system and was verified by Western blot as well as mass spectrometry assays. In the primary hepatocytes culture, the recombinant gCtrp9 could inhibit the glucose production after 12-h treatment. After i.p. (intraperitoneal) injection with recombinant gCtrp9, in hypothalamus, mRNA expression levels of npy and orexin (orexigenic factors) decreased, whereas the expression levels of crh and pomc (anorexigenic factors) increased. Moreover, i.p. injection with the recombinant gCtrp9 could reduce the serum concentrations of glucose, TG and low-density lipoprotein cholesterol but increase the content of high-density lipoprotein cholesterol. Our studies for the first time unveil the structure of Ctrp9 and its potential role as a regulatory factor of metabolism and food intake in teleost.

A Selenium-Enriched Ziyang Green Tea Polysaccharide Induces Bax-Dependent Mitochondrial Apoptosis and Inhibits TGF-ß1-Stimulated Collagen Expression in Human Keloid Fibroblasts via NG2 Inactivation.

Keloids are fibroproliferative disorders characterized by the overabundant deposition of extracellular matrix (ECM), especially collagen and overgrowth of scar tissue in response to cutaneous injury. In this study, we isolated a selenium (Se)-containing polysaccharide (Se-ZGTP-I) from Ziyang green tea and explored its potential therapeutic effects on keloid fibroblasts formation. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that Se-ZGTP-I or neuron-glia 2 (NG2) short hairpin RNA (shRNA) significantly inhibited proliferation of human keloid fibroblasts via induction of apoptosis. Besides, the activation of caspase-3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP) were observed in keloid fibroblasts following Se-ZGTP-I (200 and 400 µg/ml) or NG2 shRNA treatment. Moreover, Western blotting analysis showed that treatment of keloid fibroblasts with Se-ZGTP-I (200 and 400 µg/ml) or NG2 shRNA resulted in an increase of pro-apoptotic protein Bax expression and a decrease in expression levels of anti-apoptotic protein Bcl-2 and NG2. In addition, type I collagen biosynthesis and protein expression in keloid fibroblasts following TGF-ß1 stimulation were decreased by Se-ZGTP-I (200 and 400 µg/ml) or NG2 shRNA management. Current findings imply that Se-ZGTP-I has a therapeutic potential to intervene and prevent keloid formation and other fibrotic diseases.

Pharmacodynamic study on insomnia-curing effects of Shuangxia Decoction in Drosophila melanogaster / 中国天然药物

The present study aimed to establish a pharmacodynamic method using the pySolo software to explore the influence of freeze-dried powders of Shuangxia Decoction (SXD) on the sleep of normal Drosophila melanogaster and the Drosophila melanogaster whose sleep was divested by light. The dose-effect and the time-effect relationships of SXD on sleep were examined. The effect-onset concentration of SXD was 0.25%, the plateau appeared at the concentration of 2.5% and the total sleep time showed a downtrend when the concentration was greater than 2.5%. The sleep time was the longest on the fourth day after SXD was given. The fruit fly sleep deprivation model was repeated by light stimulation at night. The middle dosage group (2.5%) had the best insomnia-curing effect. In conclusion, using the pySolo software, an approach for the pharmacodynamics study was established with Drosophila melanogaster as a model organism to determine the insomnia-curing effects of the traditional Chinese medicine (TCM). Our results demonstrated the reliability of this method. The freeze-dried powders of SXD could effectively improve the sleep quality of Drosophila melanogaster.

Hydrogen peroxide-mediated oxidative stress and collagen synthesis in cardiac fibroblasts: blockade by tanshinone IIA.

ETHNOPHARMACOLOGICAL RELEVANCE: We have recently reported that tanshinone IIA attenuated cardiac fibrosis in two-kidney, two-clip renovascular hypertensive rats via inhibiting NAD(P)H oxidase. However, little is known about the cellular and molecular mechanisms of tanshinone IIA mediated anti-fibrotic effects in cardiac fibroblasts after H(2)O(2) stimulation. The present study was performed to investigate whether H(2)O(2) may increase collagen synthesis in cardiac fibroblasts by affecting the expression and activity of NAD(P)H oxidase and whether the effects of H(2)O(2) on cardiac fibroblasts can be blocked by treatment of tanshinone IIA. MATERIALS AND METHODS: Cardiac fibroblasts were treated with H(2)O(2) (100 µmol/L) in the presence or absence of tanshinone IIA (1 µmol/L), NAD(P)H oxidase inhibitors diphenyleneiodonium (10 µmol/L), siRNA-p47phox, siRNA-Nox2 and siRNA-Nox4. Collagen synthesis was measured by [(3)H]proline incorporation, O(2)(-) production were determined by flow cytometry and DHE fluorescence microscopy. NAD(P)H oxidase activity was measured by lucigenin-enhanced chemiluminescence. RESULTS: H(2)O(2) induced the activity of NAD(P)H oxidase, O(2)(-) production, collagen synthesis and fibronectin expression in cardiac fibroblasts, and DPI abolished this induction. Exposure of adult rat cardiac fibroblasts to H(2)O(2) had time-dependent increase in the expression of p47phox, Nox2 and Nox4 oxidases. In addition, tanshinone IIA significantly inhibited H(2)O(2)-induced collagen synthesis via attenuation of O(2)(-) generation and NAD(P)H oxidase activity. Moreover, siRNA-mediated knockdown of p47phox, Nox2 and Nox4 inhibited H(2)O(2)-induced NADPH oxidase activity. H(2)O(2)-induced collagen synthesis and fibronectin expression were also inhibited by p47phox, Nox2 and Nox4 knock down. CONCLUSIONS: Our data show that NAD(P)H oxidase plays a significant role in regulating collagen synthesis in H(2)O(2)-stimulated cardiac fibroblasts. Inhibition of NAD(P)H oxidase with tanshinone IIA completely blocked the H(2)O(2)-stimulated collagen production, which will raise the experimental basis for using tanshinone IIA to cardiac fibrosis in clinic.

Effect of Qingre Quyu Granule (清热祛瘀颗粒) on stabilizing plaques in the brachiocephalic artery of apolipoprotein E deficient mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Qingre Quyu Granule (清热祛瘀颗粒, QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) deficient mice.</p><p><b>METHODS</b>Seventy-two male ApoE deficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method.</p><p><b>RESULTS</b>The plaque cross-sectional area in the brachiocephalic artery (23.7%, P<0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried fibrotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P<0.01); furthermore, the thickness of the fibrotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 μg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response.</p>

[Effects of selenium and/or iodine deficiency on chondrocyte apoptosis in rats].

OBJECTIVE: To explore the effects of selenium and/or iodine deficiency on chondrocyte apoptosis in articular cartilage in rats. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into selenium deficiency group, iodine deficiency group, combined selenium and iodine deficiency group, and control group. Chondrocyte apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and Bcl-2 and Bax in articular cartilage were stained by immunohistochemistry in F3 generation of rats. RESULTS: In articular cartilage, the positive rate of apoptotic chondrocytes stained by TUNEL in the upper and middle zones in selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05) were significantly higher than that in control group. The apoptotic chondrocytes were prominent in the middle zone. The positive percentage of chondrocytes apoptosis was not significantly different among these three groups (P > 0.05). Compared with the control group, the expressions of both Bcl-2 and Bax were significantly higher in the upper and middle zone in the selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05); however, the expressions of Bcl-2 and Bax were not significantly different among these three groups (P > 0.05). CONCLUSION: Selenium and/or iodine deficiency may induce chondrocyte apoptosis.