[Mechanism of bilobalide promoting neuroprotection of macrophages].

This study aims to explore the neuroprotective effect of bilobalide(BB) and the mechanisms such as inhibiting inflammatory response in macrophage/microglia, promoting neurotrophic factor secretion, and interfering with the activation and differentiation of peripheral CD4~+ T cells. BB of different concentration(12.5, 25, 50, 100 µg·mL~(-1)) was used to treat the RAW264.7 and BV2 cells for 24 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and cell counting kit-8(CCK-8) were employed to detect the cytotoxicity of BB and appropriate concentration was selected for further experiment. Lipopolysaccharide(LPS) was applied to elicit inflammation in RAW264.7 and BV2 cells, mouse bone marrow-derived macrophages(BMDMs), and primary microglia, respectively. The effect of BB on cell proliferation and secretion of inflammatory cytokines and neurotrophic factors was detected by enzyme-linked immunosorbent assay(ELISA). Spleen monocytes of C57BL/6 female mice(7-8 weeks old) were isolated, and CD4~+ T cells were separated by magnetic beads under sterile conditions. Th17 cells were induced by CD3/CD28 and the conditioned medium for eliciting the inflammation in BMDMs. The content of IL-17 cytokines in the supernatant was detected by ELISA to determine the effect on the activation and differentiation of CD4~+ T cells. In addition, PC12 cells were incubated with the conditioned medium for eliciting inflammation in BMDMs and primary microglia and the count and morphology of cells were observed. The cytoto-xicity was determined by lactate dehydrogenase(LDH) assay. The result showed that BB with the concentration of 12.5-100 µg·mL~(-1) had no toxicity to RAW264.7 and BV2 cells, and had no significant effect on the activity of cell model with low inflammation. The 50 µg·mL~(-1) BB was selected for further experiment, and the results indicated that BB inhibited LPS-induced secretion of inflammatory cytokines. The experiment on CD4~+ T cells showed that the conditioned medium for LPS-induced inflammation in BMDMs promoted the activation and differentiation of CD4~+ T cells, while the conditioned medium of the experimental group with BB intervention reduced the activation and differentiation of CD4~+ T cells. In addition, BB also enhanced the release of neurotrophic factors from BMDMs and primary microglia. The conditioned medium after BB intervention can significantly reduce the death of PC12 neurons, inhibit neuronal damage, and protect neurons. To sum up, BB plays a neuroprotective role by inhibiting macrophage and microglia-mediated inflammatory response and promoting neurotrophic factors.

Steroidal sapogenins from the aerial parts of Paris polyphylla var. yunnanensis and activity evaluation.

Phytochemical investigation of an extract of the aerial parts of Paris polyphylla var. yunnanensis resulted in the identification of three new steroidal sapogenins, namely as paripolins A-C (1-3). With the aid of comprehensive spectroscopic techniques (NMR, IR, UV, MS), the structures of all isolated compounds were elucidated and subsequently screened for anti-inflammatory activity.

[Expert consensus on human use experience research of traditional Chinese medicine].

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.

Laser-induced breakdown spectroscopy-guided synergistic phototherapy: A theranostic platform mediated by a single laser wavelength.

Currently, cancer theranostic studies have only focused on integrating existing medical imaging techniques with therapeutic modalities. Obviously, this strategy is not a real theranostic method, as diagnosis and therapy are based on different principles and require independent operation. Here, a cancer theranostic method was established by laser-induced breakdown spectroscopy (LIBS)-mediated synergistic photothermal/photodynamic therapy, which was activated by a single 1064-nm light for simultaneous tumor localization and treatment. PEGylated cobalt phosphate (CoP@PEG) nanoparticles (NPs) with strong near-infrared (NIR)-II absorbance, high photothermal conversion efficiency and a reactive oxygen species generation effect were fabricated, and they produced excellent antitumor outcomes under 1064-nm excitation, as evidenced by the substantial increase in HepG2 cell death in vitro and complete tumor elimination in vivo. Meanwhile, the diagnostic method of the LIBS imaging system used in the present study also uses 1064-nm light. The LIBS imaging system can provide fast, real-time analysis and imaging of elements and facilitate the localization of the tumor site by monitoring the distribution of CoP@PEG NPs for precise tumor treatment. We postulate that this theranostic platform will promote the development of further theranostic research.

[Consensus on collaborative ethical review of multi-center clinical trials of new drugs of traditional Chinese medicine (version 1.0)].

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.

Two pairs of bisabolane sesquiterpenoid stereoisomers, bisacurone D-G, from the rhizome of Curcuma longa L.

Phytochemical investigation of an extract of the rhizome of Curcuma longa L., resulted in the identification of four undescribed bisabolane sesquiterpenoids, namely as bisacurone D-G (1-4). With the aid of comprehensive spectroscopic techniques (NMR, IR, UV, MS), the structures of all isolated compounds were elucidated and subsequently screened for both anti-inflammatory and cytotoxic biological activities, Compounds 1 and 2 showed moderate inhibitory activity toward LPS-induced NO production on RAW 264.7 macrophages.

Dendrobium candidum aqueous extract attenuates isoproterenol-induced cardiac hypertrophy through the ERK signalling pathway.

CONTEXT: The pharmacological functions of Dendrobium candidum Wall. ex Lindl. (Orchidaceae) in cardiac hypertrophy remains unclear. OBJECTIVE: To evaluate whether D. candidum aqueous extract (DCAE) can attenuate experimental cardiac hypertrophy. MATERIALS AND METHODS: Cardiac hypertrophy in SD rats was induced by subcutaneously injection of isoproterenol (2 mg/kg), once a day for ten days. Rats were gavaged with DCAE (0.13 and 0.78 g/kg) daily for one month. At the end of treatment, measurement of left ventricular systolic pressure (LVSP), heart-to-body weight ratio (HW/BW), left ventricular/tibia length (LV/TL), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) levels, haematoxylin-eosin staining, and Masson's trichrome staining were conducted. In cultured H9c2 cells, DCAE (2 mg/mL) and U0126 (10 µM) were added 2 h before the isoproterenol (10 µM) stimulus. Phalloidin staining was used to evaluate cellular hypertrophy. The mRNA expression of ANP and BNP was measured by qRT-PCR. The expression of p-ERK was determined by immunoblotting. RESULTS: DCAE treatment significantly reduced the following indicators in vivo: (1) the LVSP (16%); (2) HW/BW (13%); (3) LV/TL (6%); (4) ANP (39%); (5) BNP (32%). In cultured H9c2 cells, phalloidin staining showed that DCAE relieved cellular hypertrophy (53% reduction). Furthermore, immunoblotting showed that DCAE can significantly inhibit p-ERK protein expression in vivo and in vitro (39% and 27% reduction, respectively). DISCUSSION AND CONCLUSIONS: DCAE prevents cardiac hypertrophy via ERK signalling pathway and has the potential for treatment of cardiac hypertrophy.

General versus local anesthesia for percutaneous radiofrequency ablation of hepatocellular carcinoma at unusual regions.

AIMS: The aim of this study is to compare the efficacy and safety of percutaneous radiofrequency ablation (RFA) under general anesthesia or local anesthesia plus intraoperative analgesia in the treatment of hepatocellular carcinoma (HCC) at unusual regions. SUBJECTS AND METHODS: From July 2012 to October 2019, 83 consecutive patients with 107 HCC lesions were treated with interventional radiology therapy. The lesions were located at some unusual regions such as diaphragmatic surface, hepatic hilum, hepatic subcapsular region, tissues near inferior vena cava, and tissues near the colon. General anesthesia was applied in 57 cases (general anesthesia group) and local anesthesia plus intraoperative analgesia was used in 26 cases (local anesthesia group). All patients were treated with transcatheter arterial chemoembolization, followed immediately by RFA. The rate of tumor inactivation, time used for placing RF needles to the scheduled sites, pain score, and complications were analyzed. STATISTICAL ANALYSIS USED: All continuous variables were tested for the normal/nonnormal distribution by Kolmogorov-Smirnov test. The t-test was used to analyze the normal distribution variables; the Mann-Whitney U-test was used to measure nonnormal distribution variables; and the Chi-square test for categorical variables. P < 0.05 was considered statistically significant. RESULTS: The treatments were successful in all patients, including 51 cases of complete response (CR) and 6 cases of partial response (PR) in the general anesthesia group and 18 cases of CR and 8 cases of PR in the local anesthesia group (P = 0.049). The time used for placing the needles to the scheduled sites was 1-5 min (mean 2 min) in the general anesthesia group and 2-9 min (mean 4 min) in the local analgesia group (P < 0.001). The pain scores ranged from 0 to 2 points (mean 1 point) in the general anesthesia group and 2-9 points (mean 5 points) in the local anesthesia group (P < 0.001). With regard to complications, seven cases had pneumothorax and four cases had slight hepatic subcapsular hemorrhage in the general anesthesia group and four cases of pneumothorax and three cases of slight hepatic subcapsular hemorrhage in the local anesthesia group, and the difference was not statistically significant between the two groups (P = 0.715). CONCLUSIONS: For HCC located at unusual regions, general anesthesia is superior to local anesthesia plus intraoperative analgesia in percutaneous RFA in reducing the difficulty of the procedure and improving the safety of RFA.

Larger regional volume of the thalamus in diarrhea-predominant irritable bowel syndrome: a cross-sectional study.

As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction in patients with irritable bowel syndrome (IBS). However, the regional morphological alterations of the thalamus in IBS are not well defined. We acquired structural magnetic resonance data from 34 patients with IBS and 34 demographically similar healthy subjects. Data processing was performed using FMRIB's Integrated Registration and Segmentation Tool (FIRST). Volumetric analysis and surface-based vertex analysis were both carried out to characterize the morphology of the thalamus and other subcortical structures. Our results suggested that the majority (31 cases) of the patients with IBS had diarrhea-predominant symptoms. Volumetric analysis revealed a larger normalized volume of the right thalamus and left caudate nucleus in patients with IBS than in healthy controls. Surface analysis indicated that the difference arose mainly from the laterodorsal nucleus of the right thalamus, and the body of the left caudate nucleus. In addition, patients with IBS had different hemispheric asymmetries of the thalamus (rightward) and caudate nucleus (leftward) from controls (leftward for the thalamus and rightward for the caudate nucleus). In general, our results indicated that patients with diarrhea-predominant IBS had enlarged thalamus and caudate nucleus volumes, as well as altered hemispheric asymmetries of these two structures, compared with healthy controls. The neuroimaging evidence of these structural alterations helps clarify the underlying pathophysiology of diarrhea-predominant IBS.

Individualized prevention against hypertension based on Traditional Chinese Medicine Constitution Theory: A large community-based retrospective, STROBE-compliant study among Chinese population.

Traditional Chinese Medicine Constitution (TCMC) theory states that individuals with a biased TCMC are more likely to suffer from specific diseases. However, little is known regarding the influence of TCMC on susceptibility to hypertension. The aim of this study is to examine the possible relationship between TCMC and hypertension. Retrospective evaluation and observation were performed using the STROBE guidelines checklist. A large community-based cross-sectional study was conducted between 2009 and 2013 in Changsha, China. TCMC was assessed using a questionnaire that included 68 items. TCMC distributions and the associations of different TCMCs with hypertension risk were analyzed. In total, 144,439 subjects underwent evaluations of TCMC and blood pressure (BP). There were significant differences in the hypertension prevalence among the various TCMC groups (P < .01). An adjusted logistic regression model indicated that those with phlegm wetness, yin deficiency, blood stasis, or qi deficiency were more likely to have hypertension. Analysis of the clinical characteristics related to TCMC indicated that different TCMCs corresponded to different hypertension classifications using Western medicine criteria; for example, phlegm wetness with hypertension was similar to obesity-related hypertension. Our results suggest that phlegm wetness, yin deficiency, blood stasis, and qi deficiency have different effects on the prevalence of hypertension. More attention should be paid to TCMCs associated with susceptibility to hypertension, and corresponding preventive and therapeutic treatments should be developed according to different TCMCs.

The Protective Effect of Aucubin from Eucommia ulmoides Against Status Epilepticus by Inducing Autophagy and Inhibiting Necroptosis.

Eucommia ulmoides Oliv. is a famous traditional Chinese medicine which exhibits anti-oxidative stress ability and neuro-protective effects. Aucubin is the predominant component of Eucommia ulmoides Oliv. Our present study is intended to investigate aucubin's potential protective effects on neurons against epilepsy in the hippocampus by establishing the lithium-pilocarpine induced status epilepticus (SE) rat model in vivo. Aucubin (at a low dose and a high dose of 5[Formula: see text]mg/kg and 10[Formula: see text]mg/kg, respectively) was administered through gavage for two weeks before lithium-pilocarpine injection. Rats were sacrificed at 4, 24 and 72[Formula: see text]h after SE induction. Pretreatment with both low-dose and high-dose aucubin significantly reduced the number of death neurons ([Formula: see text]) and increased the number of surviving neurons ([Formula: see text]) in DG, Hilus, CA1 and CA3 hippocampal regions post SE. Meanwhile, it significantly inhibited necroptosis proteins (MLKL and RIP-1) ([Formula: see text] or [Formula: see text]) and enhanced autophagy protein (Beclin-1 and LC3BII/LC3BI) prevalence in the hippocampus ([Formula: see text] or [Formula: see text]). In conclusion, aucubin appeared to ameliorate damages in lithium-pilocarpine induced SE in hippocampus, reduce the number of apoptotic neurons, and increased the number of survival neurons by inducing autophagy and inhibiting necroptosis. These original findings might provide an important basis for the further investigation of the therapeutic role of aucubin in treatment or prevention of epilepsy-related neuronal damages.

Aucubin and its hydrolytic derivative attenuate activation of hepatic stellate cells via modulation of TGF-ß stimulation.

Eucommia ulmoides is an important traditional Chinese medicine and has been used as a tonic with a long history. Aucubin is an active component extracted from Eucommia ulmoides, which has liver-protection effects. However the mechanisms are still unclear. To investigate the inhibitory effects and the underlying mechanisms of aucubin on TGF-ß1-induced activation of hepatic stellate cells and ECM deposition, Human hepatic stellate cells (LX-2 cells) were incubated with TGF-ß1 to evaluate the anti-fibrotic effect of aucubin. Western blot was used to investigate the expression of α-SMA, Col I, Col III, MMP-2 and TIMP-1. ROS production was monitored using DCFH-DA probe, and NOX4 expression was detected by Real-time PCR. Results indicated that TGF-ß1 stimulated the activation and ECM deposition of LX-2 cells. Compared with the control group, aucubin and aucubigenin both reduced the protein expression of α-SMA, Col I, Col III and MMP-2 in LX-2 cells. Aucubin and aucubigenin also suppressed the generation of ROS and down-regulated the NOX4 mRNA expression. Taken together, aucubin and aucubigenin both inhibit the activation and ECM deposition of LX-2 cells activated by TGF-ß1. Aucubin and aucubigenin are potential therapeutic candidate drugs for liver fibrosis.

[Meta-analysis of supplemented Zhenwu decoction for treating congestive heart-failure].

The paper was to systematically evaluate the clinical efficacy of supplemented Zhenwu decoction for treating congestive heart-failure. Three foreign language databases including the Cochrane Library, PubMed, EMbase and four Chinese databases including CBM, CNKI, VIP and Wanfang Database were retrieved from their establishment to July 2016 for all randomized control trials(RCTs) on supplemented Zhenwu decoction in treatment of congestive heart-failure. The references in the included RCTs were also traced. Literature selection and information extraction was completed and screened by two independent reviewers, and Meta-analysis was performed by using RevMan 5.3 software. Totally 13 clinical RCTs were included in this study, involving 982 patients. Meta-analysis results showed that as compared with western medicine alone, the total effective rate of heart function could be improved by applying supplemented Zhenwu decoction based on the western medicine[RR=1.16, 95%CI (1.10, 1.22)], with increased ejection fraction[MD=7.12, 95%CI= (3.98,10.27)], increased cardiac activity index[MD=6.92, 95%CI (5.21, 8.62)], increased stroke volume [MD=11.18, 95%CI (6.04, 16.33)], and increased heart index[MD=0.50, 95%CI (-0.29, 1.30)]. Supplemented Zhenwu decoction combined with routine treatment could improve the clinical symptoms of congestive heart-failure. However, due to the low quality in methodology and reports as well as small sample size of included RCTs in this study, more randomized double-blind trials with a large sample size are still required to verify the efficiency of supplemented Zhenwu decoction for treating congestive heart-failure.

The Effects of Phellinus linteus Polysaccharide Extracts on Cholesterol Efflux in Oxidized Low-Density Lipoprotein-Loaded THP-1 Macrophages.

The removal of excess cellular cholesterol is critical for maintaining cellular cholesterol homeostasis. Phellinus linteus polysaccharide extracts (PLPEs) is an immunomudulatory agent with a molecular weight of 153 kd. Here, we analyzed the effects of PLPEs on cholesterol efflux in oxidized low-density lipoprotein (ox-LDL)-loaded THP-1 (human acute monocytic leukemia cell line) macrophages. Various concentrations of PLPEs (5, 10, 20, and 100 µg/mL) were used to treat cells. Cholesterol efflux analysis was performed to analyze the cholesterol efflux ratio in PLPE-treated cells. Semiquantitative reverse transcription-polymerase chain reaction and Western blot analysis were conducted to assess the expression of target genes. Low dose of PLPEs (5-20 µg/mL) dose dependently enhanced cholesterol efflux to apolipoprotein A-I (ApoA-I), evidenced by promoting the expression of adenosine 5'-triphosphate (ATP)-binding cassette A1, ATP-binding cassette G1, and peroxisome proliferation-activated receptor γ, key regulators for cholesterol efflux. Moreover, GW9662, a potent antagonist of peroxisome proliferation-activated receptor γ, inhibited PLPE (20 µg/mL)-promoted cholesterol efflux to ApoA-I in a dose-dependent fashion. However, high dose of PLPEs (100 µg/mL) inhibited cholesterol efflux to ApoA-I from ox-LDL-loaded THP-1 macrophages, enhanced the production of superoxide anion, decreased mitochondrial membrane potential and ATP levels, and raised nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate oxidase subunits. Thus, these results indicate that low and high doses of PLPEs exhibit opposite effects on cholesterol efflux from ox-LDL-loaded THP-1 cells.

[Effect and Mechanism of Litchi Semen Effective Constituents on Insulin Resistance in Rats with Type 2 Diabetes Mellitus].

OBJECTIVE: To observe the effect of Litchi Semen Effective Constituents (LSEC) on insulin resistance (IR) in rats with Type 2 Diabetes Mellitus(T2DM), and to explore its mechanism. METHOD: T2DM models in rats with IR were induced by high-fat feeding combined with streptozocin, then the rats were randomly divided into four groups: model group, LSEC high-dose group (1. 87 g/kg), LSEC low-dose group(0. 47 g/kg) and rosiglitazone group(3. 87 x 10(-3) g/kg), blank group was established as control. After medication for four weeks, effects of LSEC on glucose or lipid metabolism and insulin resistance were investigated, histopathology and ultrastructure changes of pancreatic tissues were observed,Stem-loop Real-time fluorescence quantitative RT-PCR was used for evaluation of GRP78 mRNA and CHOP mRNA levels in pancreatic tissue of rats. RESULT: LSEC of high-dose group obviously improved fasting blood glucose, serum TG level and glucose tolerance in T2DM rats (P <0. 05 or P <0. 01). ISI was increased, HOMA-IR index was decreased, histopathology change of pancreatic tissue were alleviated, damaged organelle, such as endoplasmic reticulum and mitochondria were repaired in both groups of LSEC. Expression levels of GRP78 mRNA of both groups of LSEC and CHOP mRNA of high-dose group in pancreatic tissue were obviously lower than those of model group (P <0. 01). CONCLUSION: LSEC can improve glycolipid metabolism and IR, increase insulin sensitivity to cure T2DM, its effects may be attributed, at least in part, to inhibit the expression of GRP78 mRNA and CHOP mRNA.

Tomato WRKY transcriptional factor SlDRW1 is required for disease resistance against Botrytis cinerea and tolerance to oxidative stress.

WRKY proteins comprise a large family of transcription factors that play important roles in plant responses to biotic and abiotic stresses; however, only a few of tomato WRKYs have been studied for their biological functions. In the present study, we identified a Botrytis cinerea-responsive WRKY gene SlDRW1 (Solanum lycopersicumdefense-related WRKY1) from tomato. SlDRW1 is a nucleus localized protein with transactivation activity in yeast. Expression of SlDRW1 was significantly induced by B. cinerea, leading to 10-13 folds of increase than that in the mock-inoculated plants but not by Pseudomonas syringae pv. tomato (Pst) DC3000. Silencing of SlDRW1 resulted in increased severity of disease caused by B. cinerea, but did not affect the phenotype of disease caused by Pst DC3000. In addition, silencing of SlDRW1 also resulted in decreased tolerance against oxidative stress but did not affect drought stress tolerance. Furthermore, silencing of SlDRW1 attenuated defense response such as expression of defense-related genes after infection by B. cinerea. Our results demonstrate that SlDRW1 is a positive regulator of defense response in tomato against B. cinerea and oxidative stress.

Involvement of glutamate-cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury.

Large-dose or long-term use of aspirin tends to cause gastric mucosa injury, which is recognized as the major side effect of aspirin. It has been demonstrated that glutamate exerts a protective effect on stomach, and the level of glutamate is critically controlled by cystine/glutamate transporter (Xc(-)). In the present study, we investigated the role of glutamate-cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury in vitro and in vivo. Results showed that in human gastric epithelial cells, aspirin incubation increased the activity of LDH and the number of apoptotic cells, meanwhile down-regulated the mRNA expression of Xc(-) accompanied with decreased glutamate release. Similar results were seen in a rat model. In addition, exogenous l-glutamate attenuated the gastric mucosa injury and cell damage induced by aspirin both in vitro and in vivo. Taken together, our results demonstrated that acute gastric mucosa injury induced by aspirin is related to reduction of glutamate-cystine/glutamate transporter system activity.

Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer cells.

Spiramine C-D, the atisine-type diterpenoid alkaloids isolated from the Chinese herbal medicine Spiraea japonica complex, are shown to have anti-inflammatory effects in vitro. In this study, we report that spiramine derivatives of spiramine C-D bearing α,ß-unsaturated ketone induce apoptosis of Bax(-/-)/Bak(-/-) MEFs cell, which is positively corresponding their cytotoxicity of tumor cell lines including multidrug resistance MCF-7/ADR. The results indicated that oxazolidine ring is necessary, and derivatives bearing double 'Michael reaction acceptor' group would significantly increased activities both of inducing apoptosis of Bax(-/-)/Bak(-/-) cells and cytotoxicity of tumor cells. The result indicated that spiramine derivative with α,ß-unsaturated ketone group is a new anti-cancer agent with a capability of inducing apoptosis of cancer cells in Bax/Bak-independent manner.

Investigation into the toxicity of traditional Uyghur medicine Quercus infectoria galls water extract.

OBJECTIVE: Quercus infectoria galls (QIG) is being widely used in Traditional Uyghur Medicine. To gather preclinical safety information for the aqueous extract of QIG, a toxicity study was performed. METHODS: Subject animals were randomized, and divided into exposure and control groups. In the acute toxicity phase, three different doses--5, 7.5, and 10 g/kg, respectively--were administered via enema to imprinting control region (ICR) mice. An experiment using the maximum tolerance dose (MTD) i.e.10 g/kg was also performed. Data were gathered for 14 days, and study parameters were clinical signs, body weight, general behavior, adverse effects and mortality. At the day 14, major organs of the subjects were examined histologically. Chronic toxicity was also evaluated in Wistar rats for over 180 consecutive days. The rats were divided into three groups with different doses of 0.2 g/kg, 0.8 g/kg, and 2 g/kg, QIG. Furthermore, observations were carried out in rabbits to investigate if there were signs of irritation. RESULTS: In comparison to control group, acute, chronic toxicity and mortality were not significantly increased in exposure group. CONCLUSION: Study result suggests that the aqueous extract of QIG is unlikely to have significant toxicity and that clinical trials may proceed safely.