Objective To study the effects of Weibimei and its Chinese medicine portions(cortex frangulae, fennel powder, acorus tatarinowii, glycyrrhizae and asparagus) on cell cycle regulation in gastric cancer cells and growth inhibition in gastric cancer Xenografts.Methods Gastric cancer SGC-7901 cells were normally cultured and treated with Weibimei, extractum glycyrrhizae, cortex frangulae, fennel powder, acorus tatarinowii and asparagus.Then, the proliferation of SGC-7901 cells were detected by MTT assay, their effect on SGC-7901 cell cycle were measured by flow cytometry, and the expression of cell cycle related proteins were examined by Western blot.Animal models of SGC-7901 cells xenografts in nude mice were constructed to evaluate the growth inhibition effects of Weibimei and its Chinese medicine portions, and the expression of STAT3,p-STAT3, Cyclin D1, Bcl-2 and Survivin in gastric tumors were detected by immunohistochemical assays.Results Weibimei and its three kinds of Chinese medicine portions, cortex frangulae, fennel and acorus tatarinowii could obviously inhibit the proliferation of SGC-7901 cells, compared to control group, with a statistical significant difference (P<0.05).The cell cycle of SGC-7901 was arrested at G1 phase with cortex frangulae, fennel and acorus tatarinowii treatment, the expression of Cyclin A, B, D, E were decreased significantly (P<0.05).However, no significant effects was found in glycyrrhizae or asparagus group.Xenografts tumor sizes in Weibimei, cortex frangulae, fennel or acorus tatarinowi groups were much smaller than that in saline group or Triple Therapy group (three-kinds-drugs-combination for the treatment of gastric ulcer) (P<0.05).Xenografts experiments showed that the tumor growth in nude mice in Weibimei, cortex frangulae, fennel or acorus tatarinowi groups were significantly smaller than that in control group or in Triple Therapy Group (P<0.05), and phosphorylated STAT3, and STAT3 signaling targeted genes, including Bcl-2, Cyclin D1 and Survivin were all significantly down-regulated by immunostaining.Conclusion Weibimei and its Chinese medicine portions including cortex frangulae, fennel and acorus tatarinowii can could significantly inhibit the growth of SGC-7901 cells proliferation and arrested the cell cycle of G1 phase in vitro, and inhibit gastric cancer xenografts in nude mice in vivo.

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.
Alkaloids ; chemistry ; Benzodioxoles ; chemistry ; Chemistry, Pharmaceutical ; methods ; Curcumin ; chemistry ; Drug Carriers ; chemistry ; Drug Combinations ; Drug Delivery Systems ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Methylmethacrylates ; chemistry ; Particle Size ; Piperidines ; chemistry ; Polystyrenes ; chemistry ; Polyunsaturated Alkamides ; chemistry

The prescription combinations of traditional Chinese medicine (TCM) focuses on the taste and channel tropism, the Qi movement, as well as the compatibility according to multiple combination principles and medicinal property and flavor combination of several traditional Chinese medicines. With the in-depth study on the prescription compatibility, researchers have realized that the medicinal property theory is the core of TCM combinations. However, there is no definite method for combinations based on medicinal properties. In this paper, the authors put forward an method for designing prescription combinations based on bipartite graph and the greedy algorithm. With the medicinal property combinations of Siweilurong Pills for example, the authors proved this method could provide ideas for quickly choosing herbal medicines for prescription combinations, and discussed the prospect of this method in substituting previous and endangered herbal medicines and banned medicinal materials.
Algorithms ; Drug Combinations ; Drug Prescriptions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Phytotherapy

OBJECTIVETo investigate the role of lead in the expression of the renal fibrosis related nuclear factor kappaB (NF-kappaB), transforming growth factor (TGF-beta) and fibronectin (FN) in rat kidney and the possible molecule mechanism of lead induced renal fibrosis.

METHODSThirty-two Sprague-Dawley rats were randomized into 4 groups. Group A was fed with distilled water as control group. Group B, C and D were fed with the water including 0.5% lead acetate continuously for 1, 2 or 3 months respectively. At the end of treatment, the expressions of renal NF-kappaB, TGF-beta and FN were detected by immunohistochemistry and RT-PCR.

RESULTSThe immunohistochemistry analysis showed that expressions of NF-kappaB in group B, C and D (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839 respectively) were continuously increased as compared with that in group A (0.1464 +/- 0.0624). The RT-PCR analysis showed that expressions of NF-kappaB in group B, C and D (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538 respectively) were also increased as compared with that in group A (0.3608 +/- 0.0550). However, there was no change for TGF-beta in 4 groups except that it was increased markedly in group D (0.5225 +/- 0.0416) as compared with that in group A (0.4645 +/- 0.0461) by RT-PCR. The expressions of FN in group C and D (0.4243 +/- 0.0595 and 0.4917 +/- 0.0891 by immunohistochemistry; 0.8650 +/- 0.0880 and 0.8714 +/- 0.0980 by RT-PCR) were increased as compared with those in group A (0.3530 +/- 0.0490 by immunohistochemistry and 0.7432 +/- 0.0639 by RT-PCR).

CONCLUSIONThe lead can increase the expression of renal NF-kappaB, TGF-beta and FN in rats, which may be related to the lead induced renal fibrosis in rats.

Animals ; Fibronectins ; biosynthesis ; genetics ; Fibrosis ; chemically induced ; Immunohistochemistry ; Kidney ; drug effects ; metabolism ; pathology ; Lead ; toxicity ; Male ; NF-kappa B ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta ; biosynthesis ; genetics

Multi-component traditional Chinese medicines are an innovative research mode for traditional Chinese medicines. Currently, there are many design methods for developing multi-component traditional Chinese medicines, but their common feature is the lack of effective connection of the traditional Chinese medicine theory. In this paper, the authors discussed the multi-component traditional Chinese medicine design methods based on medicinal property combination modes, provided the combination methods with the characteristics of traditional Chinese medicine for the prescription combinations, and proved its feasibly with hypertension cases.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Blood Pressure ; drug effects ; Drug Combinations ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Hypertension ; drug therapy ; physiopathology ; Medicine, Chinese Traditional ; Rats

OBJECTIVETo investigate the effects of 11, 12-epoxyeicosatrienoic acids (11, 12-EET) on the degree of hypoxia/reoxygenation injury in human umbilical vein endothelial cells ( HUVECs), and reveal the possible pathway of EET on protection.

METHODSPrimary cultured HUVECs were randomly divided into control group, hypoxia/reoxygenation group, 11, 12-EET control group, 11, 12- EET hypoxia/reoxygenation group, inhibition of extracellular signal-regulated kinase (ERKI/2) group, and inhibition of nitric oxide synthase (NOS) group. Hypoxia/reoxygenation injury model in HUVECs was established by exposure to hypoxia (2% O2, 5% CO2 and 93% N2) for 3 hours, followed by reoxygenation (95% air and 5% CO2) for 1 hour. The evaluation of the endothelial cells were made by immunohistochemistry. The cell viability was monitored by MTT assay. Colorimetry method was used to assay the lactate dehydrogenase (LDH) , malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in culture medium. Western blot was used to detect the expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated ERK1/2 in HUVECs.

RESULTS11, 12-EET caused minor injury in normal oxygen incubated HUVECs; however, in hypoxia/reoxygenation HUVECs, it raised the cell viability markedly, decreased the LDH release and MDA content, and increased the activity of SOD and the expressions of eNOS and phosphorylated ERK1/2.

CONCLUSIONS11, 12-EET may prevent against endothelial cell hypoxia/reoxygenation injury. The mechanism may be related to the increased activity of SOD, elimination of oxygen-derived free radicals, and reduction of eNOS and phosphorylated ERK1/2 lesion caused by hypoxia/reoxygenation.

8,11,14-Eicosatrienoic Acid ; analogs & derivatives ; pharmacology ; Cell Hypoxia ; drug effects ; physiology ; Cell Survival ; Cells, Cultured ; Endothelial Cells ; drug effects ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Mitogen-Activated Protein Kinase 3 ; biosynthesis ; Nitric Oxide Synthase Type III ; biosynthesis ; Reperfusion Injury ; prevention & control ; Superoxide Dismutase ; metabolism ; Umbilical Veins ; cytology

OBJECTIVETo investigate the effects of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) preconditioning and postconditioning on Ca(2+)-handling proteins in myocardial ischemia/reperfusion (IR) injury in rats and reveal the effects and mechanism of 11, 12-EET on cardioprotection. METHODS The IR injury model was built by stopping perfusion for 40 minutes followed by reperfusion for 30 minutes. The isolated Langendorff-perfused rat hearts were divided into 4 groups: control group, IR group, EET preconditioning (Pre-EET) group and EET postconditioning (Post-EET) group. The computer-based electrophysiological recorder system was used to measure the changes of the maximal rate of pressure increased in the contraction phase (+dp/dt(max)), the maximal rate of pressure decreased in the diastole phase (-dp/dt(max)), the left ventricular end diastolic pressure (LVEDP) and the difference of left ventricular pressure (delta LVP). The activity of Ca(2+)-ATPase in sarcoplasmic reticulum was measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of C(a2+)-handling protein [sarcoplasic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), ryanodine receptor type 2 (RyR,), and 1, 4, 5-trisphosphate inositol receptor type 2 (IP3 R2) ] mRNAs level.

RESULTSCompared with IR group, the myocardial functions, the value of Ca(2+)-ATPase, and the expressions of IP3 R2 mRNA were significantly increased and the expression of PLB mRNA was significantly decreased in both Pre-EET group and Post-EET group (P < 0.05, P < 0.01). And the expression of SERCA mRNA was significantly increased in Pre-EET group (P < 0. 05). However, no significant differences were detected between Pre-EET and Post-EET groups. Moreover, the expression of RyR2 mRNA was not significantly different among all groups.

CONCLUSIONS11, 12-EET preconditioning and post-conditioning can protect myocardium from IR injury by elevating the activity of Ca(2+)-ATPase in sarcoplasmic reticulum, up-regulating the expression of IP3 R2 mRNA, and down-regulating the expression of PLB mRNA. Moreover, up-regulating the expression of SERCA mRNA maybe one of mechanisms of 11, 12-EET preconditioning on cardio protection against IR injury.

8,11,14-Eicosatrienoic Acid ; analogs & derivatives ; pharmacology ; Animals ; Calcium-Binding Proteins ; drug effects ; metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; drug effects ; metabolism ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Rats ; Ryanodine Receptor Calcium Release Channel ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; drug effects ; metabolism

OBJECTIVETo evaluate the effects of school entrance age on cognition and behaviors in children with attention deficit hyperactivity disorder (ADHD) using mathematical event-related potential (ERP), behavioral test, and Conners Parent Symptom Questionnaire (PSQ).

METHODSFifty-eight ADHD children aged 7-12 years were enrolled and classified into older age and younger age groups according to the school entrance age (n=29 each). The children in the older age group were admitted at an age of 6 years and 6 months to 6 years and 11 months, and those in the younger age group were admitted at an age of 6 years to 6 years and 5 months. The ERP with a mathematical task was used to detect the difference in brain electrical activity between the two groups, and the behavioral test results were compared. The children's parents were asked to complete the PSQ, and the scores on each subscale were compared.

RESULTSThe ERP detection showed that the older age group had a significantly higher P2 amplitude for wrong answers than the younger age group (10.9±5.0 μv vs 8.5±3.6 μv; P<0.05). The younger age group had a significantly shorter time of response to wrong answers than the older age group (619±340 ms vs 870±418 ms; P<0.05). The scores on the subscales of learning problems and impulse-hyperactivity of PSQ were significantly higher in the younger age group than in the older age group (P<0.05).

CONCLUSIONSSchool entrance age can affect cognition and behaviors in children with ADHD, and the ADHD children with a younger school entrance age have an obvious defect in executive function, especially the function of error detection, which leads to the prominent problems in impulse-hyperactivity and learning.

Age Factors ; Attention Deficit Disorder with Hyperactivity ; physiopathology ; psychology ; Child ; Child Behavior ; Evoked Potentials ; physiology ; Female ; Humans ; Male

OBJECTIVE: To prospectively compare facial pain outcomes for patients having either a repeat microvascular decompression (MVD) or percutaneous balloon compression (PBC) as their surgery for trigeminal neuralgia (TN) recurrence.METHODS: Prospective cohort study of 110 patients with TN recurrence who had either redo MVD (n=68) or PBC (n=42) from July 2010 until September 2016. The mean follow-up was 45.6 months.RESULTS: After redo MVD, 65 patients (95.6%) experienced immediate relief of pain. After PBC, 34 patients (81%) were immediately relieved of their neuralgia. After 1 month, the clinical effect of redo MVD was better than PBC (p < 0.01). Patients who had redo MVD more commonly were pain free off medications (93.4% at 1 year, 78.2% at 4 years) compared with the PBC patients (85.1% at 1 year, 59.3% at 4 years). However, mean length of stay was longer (p>0.05). Patients after PBC who occurred developed herpes simplex (35.7%), facial numbness (76.2%), and annoying dysesthesia (21.4%) more frequently compared with patients after redo MVD who occurred developed herpes simplex (14.7%), facial numbness (8.8%), and hypoesthesia (5.9%) (p < 0.05). The symptoms recurred respectively in 15 patients (22.1%) and 19 patients (45.2%) after redo MVD and PBC within the entire 6-year follow-up period.CONCLUSION: For the patients with TN recurrence, redo MVD was a more effective procedure than PBC. The cure rate and immediate relief of pain were better, and the incidence of complications was lower.
Cohort Studies ; Facial Pain ; Follow-Up Studies ; Herpes Simplex ; Humans ; Hypesthesia ; Incidence ; Length of Stay ; Microvascular Decompression Surgery ; Neuralgia ; Paresthesia ; Prospective Studies ; Recurrence ; Trigeminal Neuralgia

OBJECTIVETo investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin.

METHODSThe experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR.

RESULTSElectron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F.

CONCLUSIONThe potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

Animals ; Disease Models, Animal ; Fibronectins ; genetics ; metabolism ; Kidney ; drug effects ; metabolism ; ultrastructure ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Lead Poisoning ; complications ; metabolism ; pathology ; Male ; NF-kappa B ; genetics ; metabolism ; Potassium Iodide ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley