[Association of Geriatric Nutritional Risk Index with Adverse Events and Time to Treatment Failure in Malignant Lymphoma Patients Treated with(R-)EPOCH].

To date, there are no reports that examine the relationship between geriatric nutritional risk index(GNRI)at the start of chemotherapy for malignant lymphoma and adverse effects. In this study, we investigated the relationship between GNRI at the start of chemotherapy and the incidence of side effects and time to treatment failure(TTF)in(R-)EPOCH-treated patients with relapsed or refractory malignant lymphoma. A significant difference in the incidence of Grade 3 or higher thrombocytopenia was observed between high and low GNRI groups(p=0.043). The GNRI may be an indicator of hematologic toxicity in malignant lymphoma patients treated with(R-)EPOCH. There was a statistically significant difference in TTF between the high and low GNRI groups(p=0.025), suggesting that nutritional status at the start of(R-)EPOCH may affect treatment continuation.

Oxocrebanine: A Novel Dual Topoisomerase inhibitor, Suppressed the Proliferation of Breast Cancer Cells MCF-7 by Inducing DNA Damage and Mitotic Arrest.

BACKGROUND: DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong (S. hainanensis), a Li nationality plant that has abundant aporphine alkaloids, can inhibit Topo. PURPOSE: To identify a dual Topo inhibitor, a deep and systematic study of active aporphine alkaloids in S. hainanensis and their mechanisms of inhibiting breast cancer proliferation and Topo activity are essential. STUDY DESIGN: This study aimed to assess the anti-breast cancer and Topo inhibitory activities of oxocrebanine and explore the underlying mechanisms. METHODS: The growth inhibitory activities of 12 compounds in S. hainanensis were screened by MTT assay in MCF-7, SGC-7901, HepG-2 cells, and compared with the effects on human normal mammary epithelial MCF-10A cells as non cancer control cells. The Topo inhibitory activity was assessed by DNA relaxation and unwinding assays, kDNA decatenation assay and western blot. Cell cycle and autophagy analyses were carried out with flow cytometry and staining. Acridine orange staining and α-tubulin morphology were observed by fluorescence microscopy. Western blot was used to examine microtubule assembly dynamics and the expression levels of key proteins associated with DNA damage, autophagy and mitotic arrest. RESULTS: Oxocrebanine was the anti-breast cancer active alkaloid in S. hainanensis. It exhibited the best inhibitory effect on MCF-7 cells with an IC50 of 16.66 µmol/l, and had only weak effect on the proliferation of MCF-10A cells. Oxocrebanine inhibited Topo I and II α in a cell-free system and in MCF-7 cells. The DNA unwinding assay suggested that oxocrebanine intercalated with DNA as a catalytic inhibitor. Oxocrebanine regulated the levels of Topo I and IIα and DNA damage-related proteins. Oxocrebanine led to the mitotic arrest, and these effects occurred through both p53-dependent and p53-independent pathways. Oxocrebanine induced autophagy, abnormal α-tubulin morphology and stimulated enhanced microtubule dynamics. CONCLUSION: Oxocrebanine was the anti-breast cancer active aporphine alkaloid in S. hainanensis. Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator. Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.

Research Progress on G2/M Arrest in Breast Cancer Cells by Active Compounds of Traditional Chinese Medicine / 中国实验方剂学杂志

The global incidence of breast cancer has increased year by year. Breast cancer has the highest mortality rate in female patients with malignant tumors. Traditional Chinese medicine（TCM） has made great contribution to health of human being， improving the overall curative effect， reducing the patients' pain， improving the quality of life and alleviating adverse reactions in patients. TCM and its active compounds can inhibit the proliferation of breast cancer cells by inducing cell cycle arrest， invasion， metastasis and reversing multidrug resistance. The effect of the compounds in TCM is obvious on inducing the arrest of the breast cancer cells cycle. It′s a novel method to fight against breast cancer by influencing the progress of the breast cancer cell cycle and inducing the cell cycle arrest in breast cancer cells. Lots of studies have shown that the G2/M phase checkpoint which transition from gap-phase （G2 phase） to mitotic phase （M phase） in the cell cycle is the key point for cell survival or death. Many antitumor drugs can inhibit the proliferation of tumor cells through the cell cycle arrest. We summarized the domestic and foreign literatures in recent years， and comprehensively explained the research progress on the related regulatory molecules in G2/M arrest. In addition， we summarized and sorted out the researches on the methods and ways of alkaloids， polysaccharides， terpenes， flavonoids， saponins and other active compounds of TCM in inducing the G2/M arrest of human breast cancer cells. By summarizing the active compounds of various Chinese medicines in inducing G2/M arrest of breast cancer cells， and reviewing the research progress on mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells， we will， in this paper， investigate the mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells through inducing G2/M arrest of human breast cancer cells， so as to provide a scientific basis for in-depth research on the anti-breast cancer mechanism of the active compounds in TCM.

TMF, a natural dihydroflavonoid isolated from Scutellaria javanica Jungh, stimulates anticancer activity of s180 cancer-bearing mice, induces apoptosis, inhibits invasion and migration on HepG-2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: 5-hydroxy-7,8,2',6'-tetramethoxy flavanone (TMF) is a dihydroflavonoid extracted from Scutellaria javanica Jungh. It is a species of genus Scutellaria, and a representative southern herb and Li nationality medicine. The plant has been used as an ethnic medicine in treating cancer and the main components are dihydroflavonoids. However, the underlying mechanisms are yet to be elucidated. AIM OF THE STUDY: The present study aimed at investigating the efficacy of TMF in cancer and the underlying mechanisms. MATERIALS AND METHODS: The s180 cancer-bearing mice experiment in vivo was designed to study the tumor growth inhibition of TMF. Also, we investigated the latent mechanism of TMF induced apoptosis and the inhibitory action of TMF on the metastasis and proliferation in HepG-2 cells. The in vitro experimental groups were treated with TMF or hydroxycamptothecine (HCPT) for 24 h. Apoptosis was detected by flow cytometry. Caspase-3 activity was detected by ELISA. The expressions of PCNA, Bcl-2, Bax, p53, E-Cadherin, MMP-9, MMP-2, STAT3, p-STAT3, JAK2, p-JAK2, AKT, p-AKT, ERK1/2 and p-ERK1/2 were examined by Western blot. RESULTS: After oral administration of TMF in s180 cancer-bearing mice, tumor growth in vivo was suppressed significantly. The MTT assay result and the reduction of PCAN proved that TMF could inhibit HepG-2 cells proliferation. TMF also caused dose-dependent apoptosis on HepG-2 cells. The experimental results showed that the expression of Bcl-2 was reduced, and the expressions of caspase-3, Bax and p53 were increased. Therefore, we speculated that TMF-induced apoptosis might be achieved by regulating the p53-Bcl-2/Bax-caspase-3 pathways. Transwell cell migration and invasion assay showed that treatment with TMF inhibited the invasion and migration in HepG-2 cells. The expressions of MMP-9 and MMP-2 were decreased while that of E-cadherin was enhanced significantly by TMF. Additionally, the expressions of p-JAK2, p-STAT3, p-AKT and p-ERK1/2 were decreased, but those of JAK2, STAT3, AKT and ERK1/2 remained unchanged. Thus, it is indicated that TMF induced apoptosis and inhibited proliferation and metastasis on HepG-2 cells via JAK2/STAT3, MAPK/ERK and PI3K/AKT pathways. CONCLUSION: The present results demonstrated that TMF could stimulate anticancer activity of s180 cancer-bearing mice, induce apoptosis, and inhibit invasion and migration on HepG-2 cells. Our findings displayed a systematic insight into the mechanisms underlying anticancer action of TMF, and provided a better understanding of its use for cancer.

[Clinical effect of Liyan Tongqiao acupuncture in treatment of post-stroke dysphagia: an analysis based on diffusion tensor imaging].

OBJECTIVE: To investigate the clinical change of post-stroke dysphagia after the intervention of Liyan Tongqiao （relieving sore-throat and dredging orifices）acupuncture using cranial diffusion tensor imaging (DTI). METHODS: A total of 60 patients with post-stroke dysphagia were enrolled and randomly divided into Liyan Tongqiao acupuncture group and neurology treatment group, with 30 patients in each group. The patients in the neurology treatment group were given routine neurology treatment and swallowing rehabilitation training, and those in the Liyan Tongqiao acupuncture group received acupuncture at Sishencong (EX-HN1), Baihui (GV20), bilateral Tai-yang (EX-HN5), and bilateral Fengchi (GB20) and tongue triple acupuncture, with an electroacupuncture apparatus for EX-HN1, bilateral GB20, and tongue triple acupuncture, for a needle retaining time of 30 minutes each time, once a day and 5 times a week, in addition to the treatment in the neurology treatment group. Each course of treatment was 3 weeks, and both groups were treated for 2 courses. Swallowing function assessment and cranial DTI were performed after treatment. RESULTS: After 6 weeks of treatment, both groups had a marked improvement in swallowing function, a significantly greater change in video fluoroscopic swallowing study (VFSS) score and a higher mean FA value (P<0.05). Compared with the neurology treatment group, the Liyan Tongqiao acupuncture group had a marked improvement in swallowing function, a significantly greater change in VFSS score in the pharyngeal phase and a higher mean FA value (P<0.05). CONCLUSION: Liyan Tongqiao acupuncture can improve dysphagia and swallowing function in the pharyngeal phase in VFSS, possibly by promoting the remodeling of cerebral cortex and increasing the FA value of infarct zone through the stimulation of related acupoint signals.

Indigo Naturalis Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating the Intestinal Microbiota Community.

Indigo naturalis (IN) is a traditional Chinese medicine, named Qing-Dai, which is extracted from indigo plants and has been used to treat patients with inflammatory bowel disease (IBD) in China and Japan. Though there are notable effects of IN on colitis, the mechanisms remain elusive. Regarding the significance of alterations of intestinal flora related to IBD and the poor water solubility of the blue IN powder, we predicted that the protective action of IN on colitis may occur through modifying gut microbiota. To investigate the relationships of IN, colitis, and gut microbiomes, a dextran sulfate sodium (DSS)-induced mice colitis model was tested to explore the protective effects of IN on macroscopic colitis symptoms, the histopathological structure, inflammation cytokines, and gut microbiota, and their potential functions. Sulfasalazine (SASP) was used as the positive control. Firstly, because it was a mixture, the main chemical compositions of indigo and indirubin in IN were detected by ultra-performance liquid chromatography (UPLC). The clinical activity score (CAS), hematoxylin and eosin (H&E) staining results, and enzyme-linked immunosorbent assay (ELISA) results in this study showed that IN greatly improved the health conditions of the tested colitis mice, ameliorated the histopathological structure of the colon tissue, down-regulated pro-inflammatory cytokines, and up-regulated anti-inflammatory cytokines. The results of 16S rDNA sequences analysis with the Illumina MiSeq platform showed that IN could modulate the balance of gut microbiota, especially by down-regulating the relative quantity of Turicibacter and up-regulating the relative quantity of Peptococcus. The therapeutic effect of IN may be closely related to the anaerobic gram-positive bacteria of Turicibacter and Peptococcus. The inferred metagenomes from 16S data using PICRUSt demonstrated that decreased metabolic genes, such as through biosynthesis of siderophore group nonribosomal peptides, non-homologous end-joining, and glycosphingolipid biosynthesis of lacto and neolacto series, may maintain microbiota homeostasis during inflammation from IN treatment in DSS-induced colitis.

An integrative urinary metabolomic study of the therapeutic effect of Guizhi Fuling capsule on primary dysmenorrheal rats based 1H NMR and UPLC-MS.

Guizhi Fuling capsule (GFC) was an important traditional Chinese herbal medicine used for the treatment of primary dysmenorrheal (PD). The aim of this study was to evaluate the anti-dysmenorrheal effect of GFC on dysmenorrheal rats induced by oxytocin and to investigate its mechanism of action. An integrative urinary metabolomic study based on 1H NMR and UPLC-MS was used to investigate the therapeutic effect of GFC on PD rats. In addition, in order to obtain more potential biomarkers and to investigate the global urine metabolic profile associated with PD, we combined the characteristics of RP-UPLC-MS with HILIC-UPLC-MS on metabolomic platform to find non-polar and polar metabolites. Finally, a total of 36 potential biomarkers were identified as being primarily involved in the TCA cycle, gluconeogenesis, glycolysis, pentose phosphate pathway, lipid metabolism, energy metabolism, amino acid metabolism and intestinal flora metabolism, and PD could influence the balance of many of these metabolic pathways in vivo. Furthermore, these results also suggested that the GFC had therapeutic effects on PD rats via the regulation of multiple metabolic pathways. In conclusion, the variations in potential biomarkers revealed the therapeutic mechanism of GFC, and these potential biomarkers were both significant for early diagnosis and predicting PD.

Intergrated metabonomic study of the effects of Guizhi Fuling capsule intervention on primary dysmenorrheal using RP-UPLC-MS complementary with HILIC-UPLC-MS technique.

Guizhi Fuling capsule (GFC), developed from the traditional Chinese prescription of Guizhi Fuling Wan, has been commonly used for the treatment of primary dysmenorrhea (PD). However, the intervention effective mechanism in vivo has not been well elucidated. In this study, an integrated plasma metabonomic strategy based on RP-UPLC-MS coupled with HILIC-UPLC-MS technique has been developed to investigate the global therapeutic effects and intervention mechanisms of GFC on dysmenorrhea rats induced by oxytocin. The 20 potential biomarkers were identified and primarily related to sphingolipid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, amino acid metabolism, lipid metabolism and energy metabolism. The results showed that the GFC has therapeutic effects on rats with dysmenorrhea via the regulation of multiple metabolic pathways. Some new potential biomarkers associated with primary dysmenorrhea such as phenylalanine, tryptophan, taurine, carnitine, betaine, creatine and creatinine have been discovered in this study for the first time. This study provides a metabonomic platform based on RP-UPLC-MS complementary to HILIC-UPLC-MS technique to investigate both nonpolar and polar compounds, so as to get a more comprehensive metabolite information to yield insight into the pathophysiology of PD and assessing the efficacy of GFC on PD rats.

Tissue metabolomic profiling to reveal the therapeutic mechanism of reduning injection on LPS-induced acute lung injury rats.

Acute lung injury (ALI) is a severe respiratory disease. To date, no medical interventions have been proven effective in improving the outcome. Reduning injection (RDN) showed a potential effect in the therapy of ALI. However, seldom does research concern the holistic pharmacological mechanisms of RDN on ALI. A metabolomic strategy, based on two consecutive extractions of the lung tissue, has been developed to investigate therapeutic mechanisms of RDN on ALI model rat. The extraction procedure was an aqueous extraction with methanol-water followed by organic extraction with dichloromethane-methanol. According to the lipophilicity of extracts, aqueous extracts were analyzed on the T3 column and organic extracts on the C18 column. Partial least-squares discriminant analysis was utilized to identify differences in metabolic profiles of rats. A total of 14 potential biomarkers in lung tissue were identified, which mainly related to phospholipid metabolism, sphingolipid metabolism, nucleotide metabolism and energy metabolism. The combined analytical method provides complementary metabolomics information for exploring the action mechanism of RDN against ALI. And the obtained results indicate metabolomics is a promising tool for understanding the holism and synergism of traditional Chinese medicine.

The usage of electronic resources to carry out the service of Traditional Chinese Medical knowledge / 国际中医中药杂志

The article introduces the character and the electronic resource of Library of China Academy of Chinese Medical Sciences's collection,mainly expatiates how to develop the knowledge service from three aspects:electronic resources serve evidence-based medicine,the frontier of traditional Chinese medicine and the knowledge of TCM found and utilization.

Optimization of synthesis, characterization and cytotoxic activity of Seleno-Capparis spionosa L. polysaccharide.

In this study, an experiment was designed to optimize the synthesis of seleno-Capparis spionosa L. polysaccharide (Se-CSPS) by response surface methodology. Three independent variables (reaction time, reaction temperature and ratio of Na(2)SeO(3) to CSPS) were tested. Furthermore, the thermal stability, particle size, shape and cytotoxic activity of Se-CSPS in vitro were investigated. The optimum reaction conditions were obtained shown as follows: reaction time 7.5 h, reaction temperature 71 °C, and ratio of Na(2)SeO(3) to CSPS 0.9 g/g. Under these conditions, the Se content in Se-CSPS reached 5.547 mg/g, which was close to the predicted value (5.518 mg/g) by the model. The thermal stability, particle size and shape of Se-CSPS were significantly different from those of CSPS. Additionally, a MTT assay indicated that the Se-CSPS could inhibit the proliferation of human gastric cancer SGC-7901 cells in a dose-dependent manner.

[Study on apoptosis effect induced by isothiocyanates in broccoli on HepG-2 cells and its mechanism].

OBJECTIVE: To investigate the apoptosis effect of isothiocyanates (ITCS) on human liver cancer cells HepG-2, and its mechanism. METHOD: HepG-2 cells were treated with different concentrations of ITCS. MTT assay was used to evaluate the influence of ITCS on cell proliferation. Flow cytometry was used to test ROS levels, intracellular mitochondrial transmembrane potential (deltapsim) , and hypodiploid apoptosis peak in HepG-2 cells. RESULT: ITCS obviously inhibited proliferation of HepG-2 cells. When treated with 15, 30, 60, 120, 240 microg x mL(-1) of ITCS for 24 h, ROS levels were (23.1+/-1. 8)%, (53.3+/-3.3)%, (57.9+/-2.0)%, (79.9+/-3.4)%, (93.4+/-2. 6)% respectively; and deltapsim were (94.8+/-5.5)%, (91.8+/-5.4)%, (66.0+/-5.6)%, (65. 5+/-6.6)% and (44.3+/-2.7)% respectively; when treated with 60, 120, 240 microg x mL(-1) of ITCS for 48 h, cell apoptotic rates were (16.6+/-2.8)%, (21.9+/-4.4) % and (70.2+/-5.3) % respectively. CONCLUSION: ITCS generates ROS in gastric cancer HepG-2 cells, which causes mitochondrial membrane permeabilization and deltapsim decrease, therefore, leads to apoptosis of HepG-2 cells.

Study on apoptosis effect induced by isothiocyanates in broccoli on HepG-2 cells and its mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the apoptosis effect of isothiocyanates (ITCS) on human liver cancer cells HepG-2, and its mechanism.</p><p><b>METHOD</b>HepG-2 cells were treated with different concentrations of ITCS. MTT assay was used to evaluate the influence of ITCS on cell proliferation. Flow cytometry was used to test ROS levels, intracellular mitochondrial transmembrane potential (deltapsim) , and hypodiploid apoptosis peak in HepG-2 cells.</p><p><b>RESULT</b>ITCS obviously inhibited proliferation of HepG-2 cells. When treated with 15, 30, 60, 120, 240 microg x mL(-1) of ITCS for 24 h, ROS levels were (23.1+/-1. 8)%, (53.3+/-3.3)%, (57.9+/-2.0)%, (79.9+/-3.4)%, (93.4+/-2. 6)% respectively; and deltapsim were (94.8+/-5.5)%, (91.8+/-5.4)%, (66.0+/-5.6)%, (65. 5+/-6.6)% and (44.3+/-2.7)% respectively; when treated with 60, 120, 240 microg x mL(-1) of ITCS for 48 h, cell apoptotic rates were (16.6+/-2.8)%, (21.9+/-4.4) % and (70.2+/-5.3) % respectively.</p><p><b>CONCLUSION</b>ITCS generates ROS in gastric cancer HepG-2 cells, which causes mitochondrial membrane permeabilization and deltapsim decrease, therefore, leads to apoptosis of HepG-2 cells.</p>