Dehydroabietic acid chemosensitizes drug-resistant acute lymphoblastic leukemia cells by downregulating survivin expression

@# Objective: To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells. Methods: Acute lymphoblastic leukemia cells REH and CCRF- CEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay, human active caspase-3 Quantikine ELISA kit, and flow cytometry. Vincristine-resistant REH cells (REH-R), survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance. Additionally, in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine. Results: Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells. Survivin expression was upregulated in REH-R cells compared with REH cells. Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine. Akt phosphorylation was also increased in REH-R cells compared to REH cells. In addition, LY294002, a PI3k/Akt pathway blocker, inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells. Dehydroabietic acid effectively reduced survivin expression in REH-R cells, thereby enhancing the therapeutic effect of vincristine on drug-resistant cells. Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine. Moreover, the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia, compared with vincristine treatment alone. Conclusions: Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.

Panax notoginseng saponins prevent colitis-associated colorectal cancer development: the role of gut microbiota / 中国天然药物

Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.

Quantification of Panax notoginseng saponins metabolites in rat plasma with in vivo gut microbiota-mediated biotransformation by HPLC-MS/MS / 中国天然药物

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.

Phenolic constituents from Oplopanax horridus / 中国中药杂志

The chemical constituents were isolated and purified by various chromatographic techniques indluding silica gel, reverse phase silica gel, sephadex LH-20 and pre-HPLC and identified by their physicochemical properties and spectral data. Sixteen phenolic compounds had been isolated and n-butanol extracts which were fractionated from the ethanol extract of Oplopanax horridus roots bark. Their structures were identified as below, including 7 phenylpropanoid compounds, ferulic acid (1), 3-acetylcaffeic acid (2), caffeic acid (3), homovanillyl alcohol 4-O-beta-D-glucopyranoside (4), 3-hydroxyphenethyl alcohol 4-O-beta-D-glucopyranoside (5), 3, 5-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (6), and 3-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (7). Three coumarins, scopoletin (8), esculetin (9) and 3'-angeloyl-4'-acetyl-cis-knellactone (10). And 6 lignan compounds, (+)-isolaricires-inol-9'-O-beta-D-glucopyranoside (11), 3, 3'-dimethoxy-4, 9, 9'-trihydroxy-4', 7-epoxy-5', 8-lignan-4, 9-bis-O-beta-D-glucopyranoside (12), (+)-5, 5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (13), (-)-5,5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (14), (-)-pinoresinol 4'-O-beta-D-glucopyranoside (15), and (+)-5, 5'-dimethoxylariciresinol 9'-O-beta-D-glucopyranoside (16). All compounds were isolated and identified for the first time from this plant All the constituents except compounds 4, 6, 12 and 13 were obtained for the first time from the genus Oplopanax.

3D finite element model of human knee injuries in the traffic accident / 法医学杂志

OBJECTIVE@#To explore the injury mechanism of the human knee in a traffic accident by establishing a 3D finite element (FE) model.@*METHODS@#The FE model, composed of femur, tibia, fibula, patella, meniscus, knee ligaments and surrounding soft tissues, was reconstructed by CT scanning data from a male volunteer. Validation was performed by the lateral impact simulation, and the stress and strain results were obtained to be compared with those previously reported for injury prediction.@*RESULTS@#The results derived from the FE model were found to be similar with those previously reported, most of the ligaments and meniscus wounded at 40 m/s collision, which was readily observed.@*CONCLUSION@#The simulation results generated by FE model can be effectively used for the injury mechanism analysis of initial contact.

Study on chemical constituents from stem of Dendrobium aphyllum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the active constituents of Dendrobium aphyllum.</p><p><b>METHOD</b>Various chromatographic techniques were used to isolate and purify the constituents, their physico-chemical properties and spectral data are determinated to elucidate the structure.</p><p><b>RESULT</b>Eight compounds were isolated and identified as: 4'-methoxyl-tricin (1), tricin (2), 7, 3', 5'-tri-O-methyl-tricetin (3), syringic acid (4), ( + )-syring-aresinol (5), D-allitol (6), sucrose (7), icariside D2 (8).</p><p><b>CONCLUSION</b>Compounds 1-3, 6-8 were isolated from genus Dendrobium for the first time, additionally, the others were obtained firstly from the plant.</p>

Chemical constituents from Hedyotis diffusa / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents from Hedyotis diffusa.</p><p><b>METHOD</b>The compounds were isolated and purified by various chromatographic techniques and identified by their physicochemical properties and spectral data.</p><p><b>RESULT</b>Eight compounds were isolated and identified as octadecyl (E)-p-coumarate (1), p-E-methoxy-cinnamic acid (2), ferulic acid (3), scopoletin (4), succinic acid (5), aurantiamide acetate (6), rubiadin (7), robustaquinone D (8).</p><p><b>CONCLUSION</b>Compounds 1-8 were obtained from genus Hedyotis for the first time.</p>

Phenolic components from herbs of Dendrobium aphyllum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the phenolic constituents of Dendrobium aphyllum.</p><p><b>METHOD</b>Various chromatographic techniques were used to isolate and purify the constituents, their physico-chemical properties and spectral data were employed to elucidate their structures.</p><p><b>RESULT</b>Nine bibenzyls and two benzylethanyl compounds were isolated and identified as: moscatilin (1), gigantol (2), batatasin (3), tristin (4), 3, 5, 4'-trihydroxylbibenzyl (5), 3, 5-dimethoxyl-4, 4'-dihydroxylbibenzyl (6), moscatin (7), 2, 4, 7-trihydroxyl-9, 10-dihydrophenanthrene (8), hircinol (9), 2-(4-hydroxyphenyl) ethyl-beta-D-glucopyranoside, salidroside (10) and p-hydroxylbenzylacetic acid (11).</p><p><b>CONCLUSION</b>All compounds were obtained firstly from the plant, and the compounds 10 and 11 were isolated in this genus for the first time.</p>

Effect of Rongshi granule on renal stone formation and osteopontin expression in rat urolithiasis model / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Rongshi granule on osteopontin(OPN) expression.</p><p><b>METHOD</b>The urlisthiasis rats were induced by ethylene glycol (EG) and ammonium chloride, the control group rats were non-treated, and the Rongshi granule groups (low-dose group, middle-dose group and high-dose group) were administered Rongshi granule in addition to EG and ammonium chloride in 21 days. Pooled 24 h urine samples from each group were collected weekly with the use of metabolic cages, the concentration of uric calcium and oxalic acid were respectively measured by EDTA and photoelectric colorimetric method. Eight animals from each group were killed at 0, 7, 14, and 21 days, kidneys were histologic examinaed and immunohistochemical staining.</p><p><b>RESULT</b>The expression of kidney osteopontin in model group was obviously higher than that of control group (P <0.01), and was up to the highest at 21 days with 1.4 times (0.281 3/0.201 8) of the control group. The expression of kidney osteopontin in all of the Rongshi granule groups were lower than those of model group (P < 0.05), with an obvious dose-dependent manner. The degree of the kidney calcium oxalate crystal of the rats in all the Rongshi granule groups was much lower than that of model group, and the uric calcium and oxalic acid were much lower than those of model group (P < 0.01).</p><p><b>CONCLUSION</b>The Rongshi granule could inhibit the expression of osteopontin in rat urolithiasis model.</p>

The rat model of erectile dysfunction caused by cavernous nerve injury / 中华男科学杂志

<p><b>OBJECTIVES</b>To identify rat cavernous nerve and establish a rat model of erectile dysfunction (ED) caused by injury of cavernous nerve.</p><p><b>METHODS</b>Twenty rats were undergone dissections. Cavernous nerves were identified with the aid of operating microscope and confirmed by electrical stimulation. Then, 42 experimental rats were randomized into 3 groups, including sham operated controls, unilateral and bilateral cavernous nerve ablation groups. Three weeks after surgery, rat models were evaluated with Apomorphine Test.</p><p><b>RESULTS</b>The major pelvic ganglion lies on either side of the dorsolateral lobes of the prostate. It includes 2 inflows, one called hypogastric nerve and another is pelvic nerve. The largest outflow is termed as cavernous nerve. Stimulus parameters which could induce obvious penile erection were 5 volts, frequency of 20 Hertz and duration of 5 milliseconds. Three weeks after surgery, apomorphine could induce penile erection of each rat in controls with mean (2.57 +/- 1.40) erections in 30 minutes, while there were no erections (0.00 +/- 0.00) either in unilateral or bilateral group.</p><p><b>CONCLUSIONS</b>The rat of larger ganglion and its cavernous nerve can be easily identified, obvious response to electrical stimulation, low cost of animal purchase, easy housing and availability made rat as an ideal animal for establishing ED model caused by cavernous nerve injury. In addition, our study showed in the early period of cavernous nerve injury, either unilateral or bilateral, all rats lost their erectile function.</p>

Therapeutic Effect of Bergamots Volatile Oil on Asthma / 实用儿科临床杂志

Objective To explore the effect of bergamots volatile oil on relieving cough,asthma and eliminating phlegm in asthmatic rats and guinea-pig.Methods Bergamot essential oil was extracted by steam distillation,and the experimental guinea-pigs and mice were divi-ded into 3 groups with high,moderate and low doses of bergamot essential oil respectively(1.080,0.540,0.108 g?kg-1for guinea pig,1.753,0.877,0.175 g?kg-1 for mice).The other group were pre-treated with normal saline as model control group,and animals were fed with acute-brochisis-syrup,aminophylline,and xianzhuli oral-liquid as positive drug control groups.After the medication,the guinea pigs were sprayed with citric acid or histamine in a confined glass to induce cough or asthma,while the latent period of cough or asthma attack was detected.The mice were injected phenol red solution through the abdominal cavity,and the tracheal phenol red secretion volume was measured.Results The latent period of cough in high,moderate and low dose of bergamot volatile oil groups and acute-brochisis-syrup group were significantly longer than that of the model control group(Pa