This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components β-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100β), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.
Animals ; Mice ; Tumor Suppressor Protein p53 ; Proto-Oncogene Proteins c-akt ; Molecular Docking Simulation ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Microcirculation ; Phosphatidylinositol 3-Kinases/genetics* ; Tumor Necrosis Factor-alpha ; ErbB Receptors ; Cerebral Hemorrhage/drug therapy* ; Neoplasms ; Phosphatidylinositols ; Drugs, Chinese Herbal/pharmacology*

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Ganoderma ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/genetics*

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro, and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.
Animals ; Apoptosis ; Cell Line, Tumor ; Humans ; Male ; Mannose ; Membrane Potential, Mitochondrial ; Mice ; Mitochondria ; Prostatic Neoplasms ; Reactive Oxygen Species

Aim To explore the role of miR-5088-5p in hepatocyte pyroptosis induced by homocysteine. Methods Hepatocytes were cultured and divided into control group and Hcy group. After transfected miR-5088-5p NC and miR-5088-5p mimic under Hcy treatment, the expression of NLRP3, Caspase 1 and IL-1β was detected by Western blot. The expression of miR-5088-5p was detected by RT-qPCR. CBS

Hematoma/etiology* ; Humans ; Percutaneous Coronary Intervention/adverse effects* ; Retroperitoneal Space

Objective To investigate the effect of miR-106b on the apoptosis and proliferation of nasopharyngeal carcinoma (NPC ) cells. Methods We analyzed differences in miRNA expression in nasopharyngeal carcinoma and adjacent normal tissues with miRNA microarray.Taq Man miRNA detection kit and Real-time fluorescence quantitative PCR were used to detect the expressions of miR-106 and RhoC mRNA in nasopharyngeal carcinoma and adjacent tissues.The miR-106b and target gene binding sites were predicted with miRnada.The target gene was verified by double luciferase.Western blot was used to detect the expression of RhoC regulated by miR-106b.Annexin and TUNEL were used to detect the effect of miR-106b on the apoptosis of nasopharyngeal carcinoma cells;the effect of miR-106b on the proliferation of nasopharyngeal carcinoma cells was detected by MTT assay.Results miRNA microarray analysis showed that the expression of miR-106b was lower in NPC tissues than in adjacent normal tissues.The results of RT-PCR showed that the expression of miR-106b in nasopharyngeal carcinoma was decreased (P <0.05)while the expression of RhoC was increased in nasopharyngeal carcinoma (P <0.05).The expressions of miR-106b and RhoC in NPC were negatively correlated (r =-0.5866, P <0.001).The results of luciferase reporter assay showed that the activity of luciferase in miR-106b group was lower than that in empty plasmid group (P < 0.05 ).The results of Western blot showed that miR-106b could decrease the expression of RhoC in NPC tissues (P <0.05).Annexin V-PI and TUNEL showed that the apoptosis ofnasopharyngeal carcinoma cells was significantly higher in miR-106 group than in empty plasmid group (P <0.05). MTT results showed that the proliferation of nasopharyngeal carcinoma cells in miR-106b group was lower than that in empty plasmid group (P <0.05).Conclusion miR-106b may induce the apoptosis of nasopharyngeal carcinoma cells and inhibit the proliferation of nasopharyngeal carcinoma cells by down-regulating the expression of RhoC.

OBJECTIVETo investigate the mothod and therapeutic efficacy of total hip anthroplasties (THA) for osteoarthritis secondary to Crowe type IV developmental dysplasia of hip in adults.

METHODSFrom May 2006 to December 2013, THA was performed on 15 adult patients (17 hips) with Growe type IV acetabular dysplasia, including 13 females and 2 males, with a mean age of 30.9 years old (22 to 58 years old) and an average preoperative Harris score of (34.0 ± 6.5) points. Traction of the affected limb was not performed before surgery. After extensive release and lengthening of soft tissues, sub-trochanteric osteotomy of the femur was performed, hip joint center was rebuilt and the abduction function was restored.

RESULTSThe patients were followed up with a mean period of 33 months (ranged from 6 months to 5 years). The postoperative Harris score was 85.0 ± 7.3,higher than the preoperative score. The extended length of limb ranged from 1.6 to 5.4 cm, with a mean of (3.42 ± 0.65) cm. The shortening and malformation of the affected limb were corrected in the most patients,with the difference in length of the two legs less than 1.5 cm. After surgery, 1 patient experienced partial sciatic nerve injury, which was largely recovered after 3 months of conservative treatment. One patient experienced complete sciatic nerve injury, which was partially recovered after 6 months of conservative treatment; a foot-drop varus deformity was formed in the distal end of the affected limb, which was improved after tendon transposition and transplantation. Joint pain was relieved, and the joint function was restored significantly. Over the follow-up period, no severe complications such as dislocation, infection, prosthesis loosening, or subsiding occurred.

CONCLUSIONSatisfactory efficacy can be achieved for adult Growe type IV acetabular dysplasia associated with osteoarthritis by THA, with proper soft tissue release and lengthening, sub-trochanteric osteotomy of femur, joint functional restoration, appropriate choice of prosthesis, and careful protection of nerves and vessels.

Adult ; Arthroplasty, Replacement, Hip ; methods ; Female ; Hip Dislocation, Congenital ; complications ; Humans ; Leg Length Inequality ; therapy ; Male ; Middle Aged ; Osteoarthritis, Hip ; surgery

Objective To provide basic references for the utilization of health educational prescription in community and to evaluate the intervention effects of health educational prescription in child vaccinoprophylaxis. Methods A total of 1055 participants ( age ranged from 1-24 months ) along with their parents were recruited from the community received routine health education about vaccinoprophylaxis. Participants were randomly divided into control group (n=495) and intervention group (n=560). All parents in the control group received the conventional health education, while parents in the intervention group received the additional health education prescription based on the conventional health education. The rate of adverse reaction of vaccinoprophylaxis in children and the satisfaction level in parents for health care were compared between two groups after six months′ interventions. Results The incidence rate of adverse reaction in the intervention group were lower than that of the control group (P<0. 01). The satisfaction level of parents in the intervention group was 97. 3% and was 90. 9% in the control group (χ2 =4. 24,P<0. 05). Conclusions The health educational prescription can reduce the incidence of adverse reaction in children and improve the satisfaction level in parents. It is worthy of promotion in community child vaccinoprophylaxis.

To investigate the clinical value of 1H magnetic resonance spectroscopy (1H MRS) in the evaluation of high intensity focused ultrasound (HIFU) ablation for primary liver cancer. Routine magnetic resonance sequences, contrast-enhanced magnetic resonance imaging and respiratory-triggered single voxel point resolved spectroscopy sequence (PRESS) were performed on 24 patients with primary liver cancer before and after HIFU ablation. A respiratory-triggered axial T2 weighted imaging (T2WI) was used as localizer for PRESS. Spectroscopy data was transmitted to a personal computer and was post-processed with a custom software (Saker, provided by Ning Jing, an engineer in GE Healthcare). It would be considered "technical success" if the baselines of spectra were stable and main metabolites were without overlapping and could be identified. Integral areas of choline (Cho) peak at 3.2 parts per million (ppm) and lipid (Lip) peak at 1.3 ppm were measured, and the choline to lipid (Cho/Lip) ratios were calculated. The differences of areas of Cho, Lip peak and Cho/Lip ratios before and after HIFU ablation were compared by using paired samples t test, and a P value of less than 0.05 was considered statistically significant. The technical success rate of 1H-MRS was 87.50% (42/48). Integral areas of Cho peak and Lip peak of 20 patients with satisfied spectra were measured, and the Cho/Lip ratios were calculated. The Integral area of Cho peak decreased from 34 597+/-6 802 before HIFU ablation to 6 372+/-2 466 after HIFU ablation (t = 18.02, P less than 0.01). The Integral area of Lip peak increased from 147 948+/-16 317 before HIFU ablation to 149 069+/-16 345 after HIFU ablation (t = -15.11, P less than 0.01). The Cho/Lip ratio decreased from 0.23+/-0.03 before HIFU ablation to 0.04+/-0.02 after HIFU ablation (t = 25.32, P less than 0.01). 1H-MRS could provide information of metabolites changes of primary liver cancer after HIFU ablation and could be used as a complementary sequence to other magnetic resonance sequences to evaluate all around primary liver cancer after HIFU ablation.

BACKGROUNDThe high mobility group A1 (HMGA1) proteins are architectural transcription factors found to be overexpressed in lung adenocarcinoma. Lentivirus-mediated RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in human cancer cells. Our preliminary study shows that gemcitabine inhibits growth of the human lung cancer cell line SPCA-1 and induces apoptosis, and this effect might link with down-regulation of HMGA1 expression. This study aimed to investigate the chemosensitivity change of the lung adenocarcinoma cells SPCA-1 after HMGA1 inhibition by lentivirus-mediated RNAi.

METHODSWe studied a highly malignant lung adenocarcinoma cell line (SPCA-1 cells). Lentiviral short-hairpin RNA (shHMGA1) expression vectors targeting HMGA1 were used for generation of lentiviral particles. After being transfected into the lung adenocarcinoma cell line SPCA-1, the expression of HMGA1 was determined by retrotranscriptase polymerase chain reaction (RT-PCR) and Western blotting. The effect of gemcitabine on proliferation of positive and negative cells was observed by methyl thiazolyl tetrazolium (MTT) assay and clonogenic survival assay. Apoptosis was observed by flow cytometery. Chemosensitivity to gemcitabine was determined by IC50 analysis. Caspase activity was quantitated by a caspase colorimetric protease assay kit.

RESULTSHMGA1-siRNA silenced its target mRNA specifically and effectively in SPCA-1 cells. The apoptotic rates of the scramble control group were (7.43 ± 0.21)%, (11.00 ± 0.20)%, and (14.93 ± 0.31)%, and the apoptotic rates in the silenced group were (9.53 ± 0.42)%, (16.67 ± 0.45)%, and (25.40 ± 0.79)% under exposure to 0.05, 0.5 and 5.0 µg/ml of gemcitabine (P < 0.05). The IC(50) of the silenced group was (0.309 ± 0.003) µg/ml which was significantly lower than in the scramble control group, (0.653 ± 0.003) µg/ml (P < 0.05). It reduced cancer cell proliferation and increased apoptotic cell death after being treated with gemcitabine compared with the scramble control group. HMGA1 silencing resulted in reduction in the phosphorylation of Akt, and promoted the activation of caspases 3, 8 and 9 upon exposure to gemcitabine.

CONCLUSIONSLentivirus-mediated RNA interference of HMGA1 enhanced chemosensitivity to gemcitabine in lung adenocarcinoma cells. The mechanism may be associated with the PI-3K/Akt signal pathway. HMGA1 may represent a novel therapeutic target in lung cancer.

Antimetabolites, Antineoplastic ; pharmacology ; Blotting, Western ; Calcium-Transporting ATPases ; genetics ; metabolism ; Caspase 3 ; genetics ; metabolism ; Caspase 8 ; genetics ; metabolism ; Caspase 9 ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Flow Cytometry ; Genetic Vectors ; genetics ; HMGA Proteins ; genetics ; metabolism ; Humans ; Lentivirus ; genetics ; RNA Interference ; physiology ; Reverse Transcriptase Polymerase Chain Reaction