Molecular Mechanism of Salviae Miltiorrhizae Radix et Rhizoma against Bladder Cancer： Based on Network Pharmacology and In Vitro Experiment / 中国实验方剂学杂志

ObjectiveTo predict the potential targets and possible related signaling pathways of Salviae Miltiorrhizae Radix et Rhizoma against bladder cancer （BC） based on network pharmacology and verify the potential molecular mechanism through in vitro cell experiment. MethodActive components of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and BC-related targets were searched from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Via Venny2.1， the potential targets of Salviae Miltiorrhizae Radix et Rhizoma against BC were screened out and the Venn diagram was plotted. Protein-protein interaction （PPI） network was constructed by STRING， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Gnomes （KEGG） pathway enrichment with DAVID. Cell Counting Kit-8 （CCK-8） assay was employed to detect the inhibitory effect of tanshinone ⅡA （Tan ⅡA）， cryptotanshinone （CPT）， and luteolin （LUT） at different concentration （0， 1， 2， 4， 8， 16， 32 μmol·L-1） on the proliferation of BC T24 and 5637 cells， propidium iodide （PI） staining to analyze the apoptosis of 5637 cells induced by Tan ⅡA， CPT， and LUT （0， 4， 8 μmol·L-1）， and Western blotting to detect the regulatory effect of Tan ⅡA （0， 4， 8， 16 μmol·L-1） on the expression of key target proteins. ResultA total of 65 active components and 39 anti-BC targets of Salviae Miltiorrhizae Radix et Rhizoma were screened out. The anti-BC targets were mainly involved in the KEGG pathways of neuron-ligand-receptor interaction， phosphatidylinositol 3-kinases （PI3K）/protein kinase B （Akt） signaling pathway， epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor resistance， and hypoxia inducible factor （HIF）-1 signaling pathway. As for the CCK-8 assay， compared with the blank group， Tan ⅡA， CPT， and LUT significantly inhibited the proliferation of T24 and 5637 cells， particularly the 5637 cells. The half maximal inhibitory concentration （IC50） of Tan ⅡA on 5637 cells was significantly lower than that of CPT and LUT. Moreover， compared with the blank group， Tan ⅡA， CPT， and LUT all induced the apoptosis of 5637 cells， and the effect followed the order of Tan ⅡA>CPT>LUT （P<0.05）. Western blot showed that Tan ⅡA significantly reduced the expression of EGFR， p-PI3K， and p-Akt in 5637 cells in a concentration-dependent manner compared with the blank group （P<0.05）. ConclusionSalviae Miltiorrhizae Radix et Rhizoma exerts therapeutic effect on BC through multiple components， multiple targets， and multiple pathways. The mechanism is the likelihood that it down-regulates the expression of EGFR， p-PI3K， and p-Akt proteins， thus further inhibits cell proliferation， and induces apoptosis.

Monomer Components of Chinese Herbal Medicines Regulate PI3K/Akt Signaling Pathway to Inhibit Bladder Cancer： A Review / 中国实验方剂学杂志

Bladder cancer is the most prevalent malignant tumor in the urinary tract in China. Western medical treatments， including long-term regular endoscopy， intravesical chemotherapy， immunotherapy， and radical cystectomy， are effective， whereas the high recurrence rate still plagues both doctors and patients. Among the classical signaling pathways involved in the formation and progression of bladder cancer， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a key one. Modern pharmacological studies have demonstrated that Chinese herbal medicines and their monomer components can alleviate the discomfort， prolong the survival， and improve the quality of life of the patients undergoing tumor treatment. The relevant literature in the past decade has revealed that flavonoids， terpenoids， polysaccharides， gambogic acids， bibenzyls， and alkaloids from Chinese herbal medicines regulate the PI3K/Akt signaling pathway to play a role in the proliferation， apoptosis， invasion， migration， drug resistance， and autophagy of bladder cancer cells， thereby exerting the activity against bladder cancer. Although some targets and the potential mechanisms of the monomer components in the treatment of bladder cancer have been clarified， the research on the monomer components is limited to in vitro cellular experiments and animal experiments. Researchers face the great challenge in the application of the monomer components from Chinese herbal medicines into clinical practice. We summarized the recent studies about the regulatory effects of monomer components from Chinese herbal medicines on the PI3K/Akt signaling pathway in bladder cancer， aiming to give insights into the research on the drug therapy of bladder cancer and the underlying mechanism.

Monomer Components of Chinese Herbal Medicines Regulate PI3K/Akt Signaling Pathway to Inhibit Bladder Cancer： A Review / 中国实验方剂学杂志

Bladder cancer is the most prevalent malignant tumor in the urinary tract in China. Western medical treatments， including long-term regular endoscopy， intravesical chemotherapy， immunotherapy， and radical cystectomy， are effective， whereas the high recurrence rate still plagues both doctors and patients. Among the classical signaling pathways involved in the formation and progression of bladder cancer， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a key one. Modern pharmacological studies have demonstrated that Chinese herbal medicines and their monomer components can alleviate the discomfort， prolong the survival， and improve the quality of life of the patients undergoing tumor treatment. The relevant literature in the past decade has revealed that flavonoids， terpenoids， polysaccharides， gambogic acids， bibenzyls， and alkaloids from Chinese herbal medicines regulate the PI3K/Akt signaling pathway to play a role in the proliferation， apoptosis， invasion， migration， drug resistance， and autophagy of bladder cancer cells， thereby exerting the activity against bladder cancer. Although some targets and the potential mechanisms of the monomer components in the treatment of bladder cancer have been clarified， the research on the monomer components is limited to in vitro cellular experiments and animal experiments. Researchers face the great challenge in the application of the monomer components from Chinese herbal medicines into clinical practice. We summarized the recent studies about the regulatory effects of monomer components from Chinese herbal medicines on the PI3K/Akt signaling pathway in bladder cancer， aiming to give insights into the research on the drug therapy of bladder cancer and the underlying mechanism.

Regulatory function of Shen-reinforcing and qi-supplementing drugs on hypothalamic-pituitary-adrenal axis and interleukin-6 dysfunction in asthmatic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Shen-reinforcing and qi-supplementing (SRQS) drugs on some ingredients of neuro-endocrine-immune (NEI) network in asthma rat model.</p><p><b>METHODS</b>Asthma model was established by ovalbumin sensitization and long-term excitation. Forty healthy Brown Norway rats of clean grade were randomly divided into 4 groups by randomized digital table, the normal control group and the three treated groups treated by low, moderate and high dose of SRQS drugs respectively. Blood content of adrenocorticotrophic hormone (ACTH) was detected by RIA; interleukin-6 (IL-6) and corticosterone were determined by ELISA; and the mRNA expresion of corticosteroid release hormone (CRH) in hypothalamus was tested by Realtime-PCR.</p><p><b>RESULTS</b>Eosinophile inflammation was shown in the pathology of asthma model rats, and also shown a multiple level hypothalamic-pituitary-adrenal axis (HPA axis) disorder at the repeated attack of asthma. After treatment, levels of ACTH and CRH mRNA expression in the treated groups were significantly higher than those in the control group (P <0.05), but the corticosterone only showed a rising tendency. Level of IL-6 increased during the episode, showing a significant negative correlation with ACTH (r = - 0.325, P = 0.043), and had somewhat reduction after SRQS treatment.</p><p><b>CONCLUSION</b>SRQS drugs could improve the function of HPH axis independent of IL-6, suggesting that the action is possibly targeted on the neuro-endocrine axis, which might be the hypothalamus.</p>

Clinical study on preventive effect of fuzheng quxie granule on respiratory viral infection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Fuzheng Quxie granule (FQG) on immune cells and cytokines of populations susceptible to respiratory viral infection.</p><p><b>METHODS</b>One thousand four hundred and two subjects selected from 25 hospitals in Shanghai between May and June in 2003, were divided into the FQG group treated with FQG and the control group treated with placebo. Serum levels of interleukin 2 (IL-2), interleukin 4 (IL-4), gamma-interferon (gamma-IFN), blood lymphocyte subsets (CD3+ , CD4+, CD8+), B-cell count and natural killer cell (NK) percent ratio were measured in 130 of the FQG group and 120 of the control group before treatment, by the end of the 2nd week and two weeks after treatment.</p><p><b>RESULTS</b>By the end of the 2nd week of treatment, as compared with before treatment, the levels of IL-2, gamma-IFN, and NK percent in the FQG group increased significantly (P < 0.05), while IL-4 and CD3+, CD4+, CD8+ and B-cell count were unchanged. Besides, levels of Th1/Th2 ratio markedly increased at the end of the 2nd week and two weeks after treatment, in comparing with that before treatment and in the control group (P<0.05).</p><p><b>CONCLUSION</b>FQG could improve immune function of population susceptible to respiratory viral infection certain extent.</p>

Effects on herba epimedii and radix Astragali on tumor necrosis factor-alpha and nuclear factor-kappa B in asthmatic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Herba Epimedii and Radix Astragali, the two Chinese herbs for replenishing Shen and strengthening qi, on tumor necrosis factor-alpha (TNF-alpha, one of the pro-inflammatory factors) and nuclear factor-kappa B (NF-kappa B) in asthmatic rats.</p><p><b>METHODS</b>Rats were randomly divided into five groups: the normal saline control group, the asthma model group and the three treated groups treated with high, medium and low dose of the Chinese herbs. Serum TNF-alpha and NF-kappa B activity in pulmonary tissue were detected with enzyme-linked immunosorbent assay and immunohistochemistry respectively.</p><p><b>RESULTS</b>Herba Epimedii and Radix Astragali could effectively reduce the production of TNF-alpha and inhibit NF-kappa B activity, and the efficacies in the three treated group were similar, showing insignificant difference among them.</p><p><b>CONCLUSION</b>Application of Herba Epimedii and Radix Astragali in the attack or remission stage of asthma could restrain the development of inflammation by reducing the production of TNF-alpha and inhibiting NF-kappa B activity.</p>

Effects of fuzheng quxie granule on immune cells and cytokines in populations with respiratory viral infection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of fuzheng quxie granule (FQG) on immune cells and cytokines in populations with respiratory viral infection.</p><p><b>METHODS</b>Fifty-nine patients were randomly divided into 3 groups, that is, 19 patients treated with conventional western medicine (WM) plus FQG in the treated group, 19 patients treated with conventional western medicine alone in the WM group, and 21 patients treated with FQG alone in the TCM group. The levels of T lymphocyte subsets, interleukine-2,4,6,10 (IL-2, IL-4, IL-6, IL-10), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma) and Th1/Th2 were determined before treatment, and at the end of 1st and 2nd week of treatment respectively.</p><p><b>RESULTS</b>Before treatment, levels of TNF-alpha, IL-2, IL-6, IL-10 and INF-gamma in all patients were significantly higher than normal range (P < 0.05). After being treated for 1 week, the levels of serum TNF-alpha, IL-6, and IL-10 were significantly decreased in all groups (P < 0.05), serum IL-2 and INF-gamma decreased to the normal level in the WM group, but in the treated and the FQG group by the end of the 2nd week, the two indexes still remained at the rather higher level (P < 0.05). The ratio of Th1 and Th2 in the treated group and the FQG group increased significantly by the end of 2nd week, reached the level higher than that in the WM group and that before treatment (P < 0.05). No significant difference in, T lymphocytes subsets (CD3+ , CD4+ , CD8+) and percentage of B and NK cells before and after treatment was found in all the 3 groups.</p><p><b>CONCLUSION</b>FQG can positively regulate the immune function of patients with respiratory tract viral infection in certain degree.</p>

Omission factors in detecting early stage prostate cancer by TRUS needle biopsy / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze and reduce the omission factors in detecting early stage prostate cancer by TRUS needle biopsy, and to improve the diagnosis of the disease.</p><p><b>METHODS</b>A total of 80 benign prostatic hyperplasia patients suspected of prostatic carcinoma underwent TRUS sextant biopsies. The pathological results being negative, the patients received transurethral resection of the prostate (TURP).</p><p><b>RESULTS</b>After TURP, 25 cases were pathologically diagnosed as prostate cancer, with an omission rate of 31.25% (25/80). Of the diagnosed cancer patients, 10 were treated by radical perineum prostatectomy, 8 by surgical castration, and 7 by medical castration.</p><p><b>CONCLUSION</b>Some tumors may fail to be detected by TRUS needle biopsy. Serial or multi-core needle biopsies can decrease the omission rate in the diagnosis of organ confined cancer.</p>

Experimental study on prevention and treatment of bronchial asthma by compound Chinese herbal monomer recipe / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of compound Chinese herbal monomer (CHM) recipe, consisted of ligustrazin (3.75 mg/kg x d), baicalin (7.5 mg/kg x d) and ginkgolide (2 mg/kg x d), on airway atopic inflammation and hyper-responsiveness in asthma.</p><p><b>METHODS</b>Model guinea pigs of asthma were randomly divided into three groups, the model group, the CHM group and the cromlyn sodium (CS) group, they were treated by atomizing inhalation with normal saline, CHM and CS respectively. The eosinophil count and eosinophil cation protein (ECP) in blood and bronchial alveolar lavage fluid (BALF), and total cell count in BALF were measured and compared. And the effect of treatment on the airway hyperresponsiveness and pathology among groups were compared.</p><p><b>RESULTS</b>CHM showed significant inhibition on blood eosinophil count and BALF and total cell count in BALF, showing significant difference (P < 0.05 or P < 0.01) as compared with those in the model group. The level of ECP was not different in the various groups. Airway responsiveness determination showed that CHM has significant inhibitory action on it. And the pathology of airway inflammation in the CHM group was significantly milder than that in the model group.</p><p><b>CONCLUSION</b>The compound inhalation liquid consisted of ligustrazin, baicalin and ginkgolide, has the anti-asthmatic airway atopic inflammation and depression on airway hyper-responsiveness, suggesting that components of compound CHM recipe could inhibit the multiple pathogenetic asthmatic inflammation from different angles and on multiple targets, so as to cure asthma effectively.</p>

Melatonin in in vitro apoptosis of H22 hepatocarcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of melatonin (MLT) in in vitro apoptosis of hepatocarcinoma cells and its mechanism.</p><p><b>METHODS</b>The apoptotic cells, bcl-2 and bax were detected through immunocytochemical method (ICC) and Tolt-mediated x-duTP nick end labeling (TUNEL). Computer image analysis system was used to quantify the expression of bcl-2 and bax by detecting the absorbance value of positive products. Apoptosis index (AI) was used to quantify the number of apoptotic cells.</p><p><b>RESULTS</b>In vitro, AI increase was both concentration- and time-dependent through TUNEL. During the same duration, AI of medium dose group was higher than that of low dose and control group (P < 0.05); AI of high dose, medium dose and 5-Fu group were higher than those of low dose and control group (P < 0.01), however, there was no significant difference between the low dose and control group (P > 0.05). At the same dose, in high dose, medium dose and 5-Fu group, the change of AI showed significant difference from 24 to 36 hours (P < 0.05). The expression of bcl-2 was down-regulated as the MLT increased, and there was significant difference between the low dose and control group (P < 0.01). But, the expression of bax was up-regulated as the dose of MLT increased, showing significant difference between the high dose and control groups (P < 0.01). As time went on, the expression of bcl-2 was decreased and in every group, with the change in absorbance value of bcl-2 significantly different from 24 to 36 hours (P < 0.05), whereas that of bax remained almost unchanged. The ratio of bax/bcl-2 was increased with the increase in the concentration of MLT.</p><p><b>CONCLUSION</b>Melatonin may induce apoptosis in the hepatocarcinoma cells which is concentration- and time-dependent, in which bcl-2 and bax are involved.</p>