Research progress in anti-colorectal cancer mechanism of berberine / 药学学报

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

Ursolic acid ameliorates azoxymethane/dextran sulfate sodium-caused colorectal cancer by inhibition of Wnt signaling cascade / 中国药理学与毒理学杂志

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

Scutellarin induces apoptosis of colorectal cancer HCT116 cells via Hippo signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro. METHODS MTT colorimetric method was used to detect the influence of scutellar?in on the survival rate of HCT116 cells. And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy. Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells. Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells. Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signal?ing pathway-related proteins Mst1, Lats1, YAP1, p-YAP(Ser127), TAZ, and its downstream effector proteins c-Myc and cyclin D1, as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells. RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells. Hoechst33342/PI double stain?ing showed that scutellarin effectively induced the apoptosis of HCT116 cells. Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1, Lats1, YAP1, TAZ and its downstream effector pro?teins c-Myc, cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin, and the expression of p-YAP (ser127) was up-regulated. Moreover, scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2, and promoted the protein level of Bax. CONCLUSION Scutellarin may inhibit the proliferation and migra?tion of HCT116 cells, while induce its apoptosis, potentially by activation of Hippo signaling pathway.

Inhibitory action of berberine on colorectal cancer HCT116 cells by regulation of Hedgehog signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigate the inhibition and mechanism of berberine on human colorectal cancer HCT116 cells through canonical Hedgehog signaling pathway. METHODS The effect of berberine on cell morphology was observed by microscopy. MTT colorimetric assay, cell scratch experiment, colony formation assay and Hoechest/PI staining were utilized to detect the activities of berberine on cell viability, cell migration and cell apoptosis. Flow cytome?try was applied to examine the cell apoptosis. The effects of berberine on caspase-3 and caspase-9 were detected by caspase activity detection kit. The expressions of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related proteins Bax and Bcl-2 as well as cell cycle-related proteins cyclin D1 were detected by Western blotting. Additionally, quantitative real time RT-PCR was employed to assess the mRNA expression levels of Hedgehog signaling pathway-related genes SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related genes Bax and Bcl-2 as well as cell cycle-related genes cyclin D1. RESULTS Berberine sharply altered the morphology of human colorectal cancer HCT116 cells, demonstrated by that migration ability of HCT116 cells was reduced significantly and the nuclei were densely stained. Berberine could induce apoptosis in a dose-dependent manner. The activities of caspase-3 and caspase-9 were increased prominently. The expression levels of Hedgehog signaling pathway-related protein SUFU and apoptosis-related protein Bax were augmented substantially. The expression levels of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, apoptosis-related protein Bcl-2 as well as cell cycle-related genes cyclin D1 were markedly lessened. Besides, the mRNA expression levels of Hedgehog signaling pathway-related gene SUFU and apoptosis-related gene Bax were augmented substantially. The mRNA expression levels of Hedgehog signaling path?way-related genes SHH, GLI1, PTCH1, SMO, apoptosis-related gene Bcl-2 as well as cell cycle-related gene cyclin D1 were markedly lessened. CONCLUSION Berberine, which is the main component of coptidis rhizoma, can remarkably restrain the growth and proliferation, promote apoptosis of human colorectal cancer cells HCT116, and the underlying mechanism may be involved in suppressing the activity of the Hedgehog signaling pathway.

Research advances in phytochemistry, pharmacology and toxicology of oleanolic acid / 中国药理学与毒理学杂志

Oleanolic acid (OA) is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1. OA is widespread in traditional Chinese herbal medicine (Ligustri Lucidi Fructus, Achyranthis Bidentate Radix, Red Sage) and berries (blueberries, grapes). In recent years, because of the extensive pharmacological effects of OA, its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers. OA has effective therapeutic effects on a series of chronic diseases such as inflammation, cancer, diabetes, and cardiovascular diseases through mul?tiple signaling pathways and various targets. Especially in cancers, such as colorectal cancer, liver cancer, gastric cancer, lung cancer, breast cancer and other malignancies, OA presents substantial efficacy. However, its poor aqueous solubility, needy bioavailability, and unsatisfactory pharmacological activity excessively restrict its clinical application. More impor?tantly, the improper utilization of OA can cause adverse reactions, toxic effects and even damage to organs in some spe?cific situations. With the discovery of various pharmacological effects, the complex action mechanisms of OA, the contin?uous progress in structural modification of OA, as well as the synthesis of OA derivatives, its application is expand?ing gradually. Among numerous studies, there is a clear indication that OA and its derivatives, if fully developed, may provide an alternative and cheaper treatment for a variety of chronic diseases. However, the specific molecular mecha?nisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer, diabetes, cardiovascular disease and other chronic diseases remain to be clarified. Therefore, it is necessary to further study the pharmacokinet?ics, pharmacological activity, specific targets and related mechanisms of OA to lay a solid foundation for drug devel?opment and the application of OA in clinical settings.

Pulsatilla chinensis:phytochemistry, pharmacology and new drug development / 中国药理学与毒理学杂志

Pulsatilla chinensis is a widely used traditional Chinese herb, which contains 56 types of chemical constit?uents, mainly including triterpenoid saponins, organic acids, coumarins and lignans. The largest portion of the ingredi?ents in Pulsatilla chinensis is the family of triterpenoid saponins, in which anemoside B4 is the major effective compound and indexing component. The main components of Pulsatilla chinensis can metabolize into a vast array of active prod?ucts in vivo, which play vital roles in its biological activity. Mounting evidence reveals that Pulsatilla chinensis exerts a wide range of therapeutic activities, such as anti-cancer, immunoregulation, anti-inflammation and anti-schistosome, with fewer adverse reactions, via various signaling pathways and multiple targets. It was documented that the active ingre?dient of Pulsatilla chinensis can lessen the drug resistance and synergize the effects of other natural products includ?ing paclitaxel, as well as ameliorate the clinical efficacy of chemical drugs, such as adriamycin. However, Pulsatilla chi?nensis was also reported to be possibly the main cause of hemolysis and chronic liver injury. The efforts should be made to deeply investigate the pharmacological actions and underlying mechanisms of Pulsatilla chinensis, with a focus on the anti-cancer efficacy, and develop new drugs based on the components of Pulsatilla chinensis for future utilization in the clinical setting.

Inhibition of colorectal cancer by ursolic acid via noncanonical Hedgehog signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo, and to explore the underlying mechanism. METHODS The smoothened (SMO) gene-silenced human colorectal cancer HCT116hSMO- cell line was established by transfection with the lentivirus carrying SMO shRNA. The cytotoxic effect of ursolic acid on HCT116hSMO-cells was determined by MTT assay. The effect of ursolic acid on the migration of HCT116hSMO- cells was studied by wound healing assay. The effect of ursolic acid on apoptosis of HCT116hSMO-cells was explored by Hoechst33342/PI double staining and flow cytometry. The effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2, Bax, caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR (RT-qPCR) and Western blotting (WB) analysis. RT-qPCR and WB were used to examine the relationship between GLI1, c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116hSMO- cells. The effects of ursolic acid on the expressions of GLI1, p-Akt, Akt, c-Myc, SHH and SUFU of nonca?nonical Hedgehog pathway were evaluated by RT-qPCR and WB assays. Xenograft nude mouse model bearing HCT116hSMO- cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in vivo. The body weight and tumor size of mice were assessed regularly every 2 d. The effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL assay. The expressions of Bcl-2, Bax, GLI1, p-Akt, Akt, c-Myc, SHH, SUFU mRNA and proteins were measured by RT-qPCR and WB. The levels of Bcl-2, Bax, GLI1, p-Akt, c-Myc and SHH proteins in tumor tissues were also evaluated by immunohistochemistry. RESULTS Ursolic acid significantly inhibited the growth and migration of HCT116hSMO-cells in vitro, compared with the control (P<0.05). Meanwhile, ursolic acid also induced apoptosis of HCT116hSMO- cells in vitro (P<0.05). Furthermore, SC79 (Akt activator) enhanced the expressions of p-Akt, GLI1 and c-Myc, which could be abolished by ursolic acid, and the effect was equal to Akt inhibitor LY294002. The expressions of Bcl-2, GLI1, p-Akt, c-Myc, SHH mRNA and proteins were reduced by ursolic acid, while the levels of Bax and SUFU were increased. Ursolic acid could inhibit the growth and induce the apoptosis of colorectal cancer xeno?graft in vivo. Similarly, lower levels of Bcl-2, GLI1, p-Akt, c-Myc and SHH, and higher expression of Bax and SUFU were noted in ursolic acid-treated mice. CONCLUSION Ursolic acid can inhibit the growth and induce apoptosis of HCT116hSMO- cells both in vitro and in vivo. And the mechanism is related to the suppression of PI3K/Akt-mediated noncanonical Hedgehog signaling pathway.

Suppression of AOM/DSS-induced colorectal cancer by scutellarin through downregulation of Wnt signaling pathway activity / 中国药理学与毒理学杂志

OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer (CAC) and its underlying mechanism based on Wnt/β-catenin signaling pathway. METHODS The mouse model of CAC was estab?lished by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by scutellarin treatment, with recording the body weight, diarrhea and hematochezia. After sacrificing the mice, the colorectal length and colorectal tumor were assessed. The levels of pro-inflammatory factors TNF-α and IL-6 in mice's sera were measured by the enzyme-linked immunosorbent assay (ELISA). The colorectal lesions were appraised by hematoxylin and eosin (H&E) staining. Theβ-catenin level in CAC tissues was probed by immunofluorescent analysis. The apoptosis-related genes Bax and Bcl-2, and Wnt signaling pathway-related genes β-catenin, GSK-3β, TCF4, c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR (RT-qPCR). Finally, Western blotting analysis (WB) was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related proteins. RESULTS Scutellarin significantly improved AOM/DSS-caused weight loss, colorectal length shortening, and tumor growth in mice (P<0.01). Meanwhile, colorectal lesions could be substantially alleviated by scutellarin. ELISA results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened (P<0.01). Scutellarin also sharply inhibited the nuclear translocation of β-catenin, as evidenced by the reduction in the nuclear level ofβ-catenin protein. In addition, scutellarin attenuated the mRNA expres?sion of Wnt signaling pathway-relatedβ-catenin, TCF4, c-Myc and cyclin D1, whereas it heightened GSK-3βmRNA level. These results were consolidated by WB analysis, which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin, TCF4, c-Myc and cyclin D1, with the increase in GSK-3β protein in CAC tissue. Moreover, scutellarin could induce the apoptosis of CAC, demonstrated by enhanced expression of Bax and diminished expression of Bcl-2 in both mRNA and protein levels. CONCLUSION Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.

Mechanism of ursolic acid in regulating colorectal cancer cell HCT116 autophagy through hedgehog signaling pathway / 中国中药杂志

To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3Ⅱ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3Ⅱ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3Ⅱ. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.

Observations on the Efficacy of Heat-sensitive Point Medicinal Moxibustion plus Percutaneous Administration of Tetrandrine in Treating Lumbar Intervertebral Disc Herniation / 上海针灸杂志

Objective To investigate the clinical efficacy of heat-sensitive point medicinal moxibustion plus percutaneous administration of tetrandrine in treating lumbar intervertebral disc herniation. Methods One hundred and twenty patients with lumbar intervertebral disc herniation were randomized to treatment and control groups, 60 cases each. The treatment group received heat-sensitive point medicinal moxibustion plus percutaneous administration of tetrandrine and the control group, heat-sensitive point medicinal moxibustion alone. The VAS score and the JOA Score for Back Pain score were recorded in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups. Results There were statistically significant pre-/post-treatment differences in the JOA Score for Back Pain score and the VAS score in the two groups (P<0.01). There were statistically significant post-treatment differences in the JOA Score for Back Pain score and the VAS score between the treatment and control groups (P<0.01). The excellent and good rate was 80.0％ in the treatment group and 55.0％ in the control group; there was a statistically significant difference between the two groups (P<0.01). Conclusion Heat-sensitive point medicinal moxibustion plus percutaneous administration of tetrandrine is an effective way to treat lumbar intervertebral disc herniation.

Effects of Weipixiao (胃痞消) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).</p><p><b>METHODS</b>Sprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.</p><p><b>RESULTS</b>Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).</p><p><b>CONCLUSION</b>Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.</p>

Correlation between low tube voltage in dual source CT coronary artery imaging with image quality and radiation dose / 华中科技大学学报（医学）（英德文版）

The influence of low tube voltage in dual source CT (DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index (BMI 0.05). The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant (P<0.05). The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant (P<0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose.

Correlation between low tube voltage in dual source CT coronary artery imaging with image quality and radiation dose / 华中科技大学学报（医学）（英德文版）

The influence of low tube voltage in dual source CT (DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index (BMI <18.5 kg/m(2)) subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C (n=100 each). The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index (CTDIvol) and dose length product (DLP) were recorded, and the effective dose (ED) was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups (P>0.05). The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant (P<0.05). The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant (P<0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose.

The effect of baicalin on human brain microvascular endothelial cell under the glucose deprivation combined with hypoxia condition / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms of baicalin on anti-cerebral ischemic through observing the effect of baicalin on human brain microvascular endothelial cell under the glucose deprivation combined with hypoxia condition.</p><p><b>METHODS</b>Human brain microvascular endothelial cells (HBMVECs) cultured in vitro were divided into the following groups: normal group, model group, baicalin high dose group, baicalin middle dose group, baicalin low dose group, nimodipine group. The kits were used to detect the cell viability, leakage rate of lactate dehydrogenase (LDH), Na(+)-K(+)-ATPase, Ca(2+)-ATPase, the concentration of Ca2+ in each group, and apoptosis rates of each group were analyzed by flow cytometry (FCM).</p><p><b>RESULTS</b>Compared with the normal group, the cell viability, Na(+)-K(+)-ATPase and Ca(2+)-ATPase in model group decreased significantly (P < 0.01, P < 0.05). But the leakage rate of LDH, Ca2+ in cells and apoptosis rates increased remarkably (P < 0.01). Compared with the model group, the cell viability, Na(+)-K(+)-ATPase and Ca(2+)-ATPase increased obviously (P < 0.01, P < 0.05) in baicalin high dose group. But the leakage rate of LDH and Ca2+ in cells in baicalin high dose group decreased significantly comparing with that of model group (P < 0.05, P < 0.01). And the reduction of intracellular Ca2+ was superior to that of nimodipine group. Meanwhile, the apoptosis rates decreased significantly in both baicalin high and middle dose groups (P < 0.01).</p><p><b>CONCLUSION</b>Baicalin could improve the cell viability of HBMVECs under the glucose deprivation combined with hypoxia condition. And the mechanisms were related with improving the energy metabolism, inhibiting intracellular calcium overload and decreasing the apoptosis rate of cells further.</p>

Comparative study on fMRI of the brain based on Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3) on human body / 中国针灸

<p><b>OBJECTIVE</b>To observe the correlation relationship between acupuncture at Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3) on the affected side of peripheral facial paralysis patients and activated areas in brain functional areas and central regulation mechanism of acupuncture at Hegu (LI 4) treatment.</p><p><b>METHODS</b>Eighteen cases with left peripheral facial paralysis were randomly divided into a Hegu group, a Dicang group and a Houxi group, 6 cases in each group. They were treated with electroacupuncture at left Dicang (ST 4), Hegu (LI 4) and Houxi (SI 3), respectively, and were examined with fMRI covering the whole brain at the same time. The fMRI data was analyzed by SPM software.</p><p><b>RESULTS</b>It was found that the left precentral gyrus area and the left postcentral gyrus area were activated when electroacupuncture at left Hegu (LI 4), and the right precentral gyrus area and the bilateral postcentral gyrus area were activated when electroacupuncture at left Dicang (ST 4), and there was no activated area at precentral gyrus area and post central gyrus area when electroacupuncture at left Houxi (SI 3).</p><p><b>CONCLUSION</b>The sensory importation information from Hegu (LI 4) and Dicang (ST 4) can converge and coincide in the brain and may influence each other.</p>

Association between delayed enhancement on cardiac magnetic resonance imaging and arrhythmia in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>to observe the association between myocardial fibrosis, detected by delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) and arrhythmia in patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>forty-eight untreated HCM patients who underwent Cine MR, DE-MRI, 24 h ambulatory Holter electrocardiogram and ECG examinations were recruited. Extent of myocardial fibrosis (fibrosis mass/total LV mass) was assessed using DE imaging. Association between arrhythmias including premature ventricular complexes (PVCS ≥ 200), supra-ventricular tachycardia (SVT), non-sustained ventricular tachycardia (NSVT), atrio-ventricular block (AVB) and intra-ventricular block (IVB) detected by Holter monitoring and ECG with regard to delayed enhancement (DE) on contrast enhanced CMR was analyzed.</p><p><b>RESULTS</b>myocardial fibrosis was detected in 35 patients. Incidence of arrhythmia was significantly higher in patients with DE than in patients without DE (P < 0.05). Extent of myocardial fibrosis was significantly associated with the QRS duration (r = 0.33, P < 0.001).</p><p><b>CONCLUSION</b>myocardial fibrosis detected by DE-CMR was associated with arrhythmia in patients with HCM. DE-CMR might be helpful to detect high-risk HCM patients prone to arrhythmia.</p>

Effect of serum from overfatigue rats on JNK/c-Jun/HO-1 pathway in human umbilical vein endothelial cells and the intervening effect of Tongxinluo superfine powder / 中国结合医学杂志

<p><b>OBJECTIVE</b>To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo superfine powder (TXLSP). By examining the variation of the activity of JNK/c-Jun/HO-1 pathway, the possible mechanisms of vascular endothelial dysfunction under overfatigue conditions and the intervening effect of TXLSP were explored.</p><p><b>METHODS</b>The HUVECs were randomly divided into the normal control group, the model group, the SP600125 (a specific antagonist of JNK) group, the TXLSP group and the TXLSP + SP600125 group. The content of carboyhemoglobin (COHb) and the leak rate of lactic dehydrogenase (LDH) in different groups were measured. The mRNA and protein expression of JNK, c-Jun, HO-1 and the phosphorylation level of c-Jun (P-c-Jun) were detected using Western blot and PCR methods.</p><p><b>RESULTS</b>Compared with the normal control group, the COHb level in supernatant was increased significantly in the model group, and the expression of HO-1, JNK, c-Jun mRNA and corresponding proteins and P-c-Jun were also increased remarkably. The increases in these parameters were significantly decreased by SP600125. TXLSP showed remarkable up-regulation on the expression of JNK, c-Jun, P-c-Jun and HO-1 mRNA and their protein expression. Compared with the SP600125 group, the expressions of JNK, c-Jun, P-c-Jun and HO-1 mRNA and its protein in the TXLSP+SP600125 group were significantly increased at different time points (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>The vascular endothelial dysfunction under overfatigue conditions is related to the activity of the JNK/c-Jun/HO-1 pathway. One of the mechanisms of TXLSP in improving the vascular endothelial function is to adjust the activity of the JNK/c-Jun/HO-1 pathway at gene and protein levels.</p>

The endothelium injuries caused by homocysteine and treatmental effects of Tongxinluo powder / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected.</p><p><b>METHODS</b>Healthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected.</p><p><b>RESULTS</b>Compared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P < 0.01), the format and percentage that capillary dilated declined significantly (P < 0.05), after treatment with Tongxinluo powder, the effect of Ach on isolated rat thoracic aorta in vitro was improved obviously (p < 0.01), and the format and percentage that capillary dilated were increased compared with model group; comparing with the control group, the level of Ang II and ET, TXA2 in plasm increased obviously (P < 0.05, P < 0.01), while the content of PGI2 depressed manifestly (P < 0.05), at the same time, both content of NO and activity of SOD, (GSH-PX declined obviously (P < 0.001, P < 0.05). After treatment with Tongxinluo powder, the level of ET, AngII and TXA2 reduced significantly in different degree (P < 0.01), while the content of PGI2 appeared stepping up notably (P < 0.01), and both activity of SOD and NO level increased obviously (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>(1) The high homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.</p>

The protective function of puerarin to the injury of the lung and its mechanisms during diabetes / 中国应用生理学杂志

<p><b>AIM</b>To evaluate the roles of puerarin in alleviating the STZ-induced lung injury.</p><p><b>METHODS</b>DM model was established by streptozotocin (STZ) intraperitoneal injection to study the injury mechanisms of the lung. SD rats were divided randomly into control group (C group), diabetes group (DM group), diabetes + puerarin group (DM + Pur group). The blood glucose and weight were observed and recorded before and the 20 th, 40 th, 60 thd after administration of saline, STS, STZ+ Pur. Contents of NO and malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were measured in lung tissues. Light microscope (LM), transmission electron microscope (TEM) and immunohistochemical analysis were also used.</p><p><b>RESULTS</b>(1) Compared with control group, the contents of NO and MDA were increased significantly (P < 0.01), while the activity of SOD reduced (P < 0.05). Compared with DM group, treatment with puerarin inhibited the increase of NO level (P < 0.01), and MDA content began to decline from 40 days after the model was established (P < 0.01), and inhibited the decrease of SOD activity induced by DM (P < 0.01). (2) LM and TEM results showed that alveolar and capillary basement membrane became thick, the number of tiny villus decreased markedly, the quantity of osmiophilic multilamellar body reduced remarkably, hyperplasia was shown in collgen fibre. Puerarin could alleviate above injuries induced by DM. (3) Immunohistochemical staining results showed that mild brown positive stain of NT could be seen in protoplasm of lung tissues. STZ administration induced the expression of NT in the protoplasm of cells, and led to stronger positive signals of NT than that of control group. Treatment with puerarin weakened the positive stain of NT.</p><p><b>CONCLUSION</b>(1) DM induced by STZ leads to a significant and sustained increase in blood glucose and obvious lung injury, which may be associated with the overproduction of free radicals. (2) The pathway of NO/ONOO- is one of the injury mechanisms of the lung tissues cells. (3) Puerarin suppresses the expression of NT and elevates the activity of SOD. Thereby, resulting in the reduces of the production of free radicals, which may be one of the mechanisms of its anti-oxidative-injuries.</p>

Study on the regulatory effect of electro-acupuncture on hegu point (LI4) in cerebral response with functional magnetic resonance imaging / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study, through blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI), the cerebral activated areas evoked by electro-acupuncturing (EA) the right Hegu point (L14) or non-acupoint points on the face, and through comparing their similarities and differences, to speculate on the specific cerebral areas activated by stimulating L14, for exploring the mechanism of its effect in potential clinical application.</p><p><b>METHODS</b>EA was applied at volunteers' right L14 (of 9 subjects in the L14 group) and facial non-acupoint points (of 5 subjects in the control group), and whole brain 3-dimensional T1 anatomical imaging of high resolution 1 x 1 x 1 mm(3) used was performed with clustered stimulatory mode adopted by BOLD fMRI. Pretreatment and statistical t-test were conducted on the data by SPM2 software, then the statistical parameters were superimposed to the 3-dimensional anatomical imaging.</p><p><b>RESULTS</b>Data from 3 testees of the 9 subjects in the L14 group were given up eventually because they were unfit to the demand due to different causes such as movement of patients' location or machinery factors. Statistical analysis showed that signal activation or deactivation was found in multiple cerebral areas in 6 subjects of L14 group and 5 subjects of the control group (P<0.01). In the L14 group, the areas which showed signal activation were: midline nuclear group of thalamus, left supra marginal gyrus, left supra temporal gyrus, right precuneous lobe, bilateral temporal pole, left precentral gyrus and left cerebellum; those which showed signal deactivation were: bilateral hippocampus, parahippocampal gyrus, amygdala body area, rostral side/ audal side of cingulate gyrus, prefrontal lobe and occipital lobe as well as left infratemporal gyrus. In the control group, areas which showed signal activation were: bilateral frontal lobe, postcentral gyrus, Reil's island lobe, primary somato-sensory cortex, cingulate gyrus, superior temporal gyrus, occipital cuneiform gyrus and/or precuneus gyrus and right brainstem; and the area that showed deactivation was left median frontal lobe.</p><p><b>CONCLUSION</b>The effects of EA L14 in regulating cerebral activities could be displayed and recorded through BOLD fMRI, the distribution of signally deactivated area evoked by EA L14 was similar to the known distribution of anatomical orientation of pain in brain, and closely related to the anatomic structure of limbic system, which areas are possibly the acupuncture analgesic effect's cerebral regulating area. Furthermore, activated portion of left central anterior gyrus, which represent the movement of oral facial muscles, and the activated portion of cerebellum are possibly related with the effect of using EA L14 in treating facial palsy and facial muscle spasm. As for the mechanism of signal deactivation of cerebral activities exhibited in the present study that is unable to be elucidated, it awaits for further research.</p>