Mechanism of astragaloside Ⅳ alleviating PC12 cell injury by activating PI3K/AKT signaling pathway: based on network pharmacology and in vitro experiments / 中国中药杂志

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.

A general description for Chinese medicine in treating premature ovarian failure / 中国结合医学杂志

Premature ovarian failure (POF) is a kind of gynecological disease that causes amenorrhea, infertility, menopause and urogenital symptoms. Currently hormone replacement therapy (HRT) is the most popular choice for women with POF to get rid of menopausal syndrome. However, as the popularization of Chinese herbs made Chinese medicine (CM) shine new lights, physicians are able to treat POF with both meno-herbs and integrated therapy. HRT has its own indications and contraindications. For example, unexplained vaginal bleeding, acute liver damage, liver dysfunction, vascular embolization, and breast cancer are all contraindications of HRT, and CM is taken by more physicians as an adjuvant therapy. This review, including a range of common Chinese herbs and formulations according to the existing literature, provides a general description of CM treating POF from the aspects of mechanisms and clinical application. It also highlights acupuncture as a unique physiotherapy for POF. Although the validity of CM has been supported by the evidence of many preclinical trials, clinical trials and meta-analysis, the adverse events with CM therapy still exist and no guarantee has been made for its safety. This review concludes the updated information for CM treating POF contributing to further studies.

Neuroprotective effects of Tongmai Yizhi Decoction () against Alzheimer's disease through attenuating cyclin-dependent kinase-5 expression / 中国结合医学杂志

<p><b>OBJECTIVES</b>To explore the protective effects of Tongmai Yizhi Decoction (, TYD), a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1-40 (Aβ) peptide and ibotenic (IBO)-induced Alzheimer's disease (AD) model rats.</p><p><b>METHODS</b>The in vivo model was established by injecting Aβand IBO into left hippocampal CA1 area of Sprague-Dawley (SD) rat to mimic AD. Totally 32 SD rats were divided into 4 groups, including sham operation group, AD model group, TYD group [AD rats treated with TYD at the dosage of 19.44 g/(kg•d) for 4 weeks] and huperzine A group [AD rats treated with huperzine A at the dosage of 40.5 μg/(kg•d) for 4 weeks]. Spatial learning and memory level was detected by Morris Water Maze test. Histological morphology in the hippocampus was tested by hematoxylin-eosin (HE) staining. Cyclin-dependent kinase-5 (Cdk5) protein and gene expression level were investigated by Western blot analysis and real-time quantitative polymerase chain reaction (RT-qPCR), respectively.</p><p><b>RESULTS</b>Aβ1-40 and IBO treatment induced longer escape latency of rats, compared with sham operation group from day 25 (P<0.01). However, TYD and huperzine A obviously shortened the escape latency from day 26 (P<0.01). Moreover, the effect of TYD was similar to huperzine A (P>0.05). Furthermore, HE staining also showed that TYD and huperzine A reversed the neuropathological changes in the hippocampus triggered by Aβ1-40 and IBO. TYD and huperzine A effectively reduced the expression levels of Cdk5 protein and gene located in rat hippocampus, compared with the AD model group (P<0.01).</p><p><b>CONCLUSION</b>TYD could be a promising neuroprotective agent for protecting neuron from AD injury through inhibiting Cdk5 expression.</p>

5-Hydroxymethylfurfural protects against ER stress-induced apoptosis in GalN/TNF-α-injured L02 hepatocytes through regulating the PERK-eIF2α signaling pathway / 中国天然药物

5-Hydroxymethylfurfural (5-HMF), a water-soluble compound extracted from wine-processed Fructus corni, is a novel hepatic protectant for treating acute liver injury. The present study was designed to investigate the protective effect of 5-HMF in human L02 hepatocytes injured by D-galactosamine (GalN) and tumor necrosis factor-α (TNF-α) in vitro and to explore the underlying mechanisms of action. Our results showed that 5-HMF caused significant increase in the viability of L02 cells injured by GalN/TNF-α, in accordance with a dose-dependent decrease in apoptotic cell death confirmed by morphological and flow cytometric analyses. Based on immunofluorescence and Western blot assays, we found that GalN/TNF-α induced ER stress in the cells, as indicated by the disturbance of intracellular Ca(2+) concentration, the activation of protein kinase RNA (PKR)-like ER kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), and expression of ATF4 and CHOP proteins, which was reversed by 5-HMF pre-treatment in a dose-dependent manner. The anti-apoptotic effect of 5-HMF was further evidenced by balancing the expression of Bcl-2 family members. In addition, the knockdown of PERK suppressed the expression of phospho-PERK, phospho-eIF2α, ATF4, and CHOP, resulting in a significant decrease in cell apoptosis after the treatment with GalN/TNF-α. 5-HMF could enhance the effects of PERK knockdown, protecting the cells against the GalN/TNF-α insult. In conclusion, these findings demonstrate that 5-HMF can effectively protect GalN/TNF-α-injured L02 hepatocytes against ER stress-induced apoptosis through the regulation of the PERK-eIF2α signaling pathway, suggesting that it is a possible candidate for liver disease therapy.

Pinching spine: A potential treatment for depression / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether pinching spine (PS, i.e. , a traditional Chinese manipulative therapy) is beneficial to ameliorating the depressive state (including behavioral deficit, retardative weight gain and decreased sucrose consumption) in a rat model of depression induced by chronic unpredictable stress (CUS) and to explore the candidate mechanism of action.</p><p><b>METHODS</b>PS was performed on rats' spine once daily for 1 week after exposure to CUS. The open-field test, body weight measuring, and sucrose intake test were applied on different dates: before stress (d0), at the end of stress (d21) and after PS treatment (d28), respectively. Then the rats' hippocampuses were performed genome-wide microarray analysis, and the expression levels of several genes were evaluated by real-time polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Exposure to CUS resulted in decreases of behavioral activity and sucrose consumption, which were reversed significantly after PS treatment. The expression of several genes relevant to energy metabolism, anti-oxidation, and olfactory receptor, etc., were down-regulated, while the expression of those relevant to hemostasis, immunity-inflammation, and restriction of activities and ingestion, etc., were up-regulated in hippocampuses of rats exposed to CUS. PS treatment significantly inverted these changes. Furthermore, increase or decrease in gene expression evaluated by realtime PCR was concordant with up-regulated or down-regulated expression evaluated by microarray analysis.</p><p><b>CONCLUSION</b>PS showed a potential antidepressant-like effect, of which the action mechanism might be due to gene expression regulation in hippocampus.</p>

Early and midterm outcomes of coronary artery bypass grafting in octogenarians / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the early and midterm postoperative outcomes and analyze risk factors of coronary artery bypass grafting (CABG) in octogenarians.</p><p><b>METHODS</b>Clinical data of 38 patients aged 80 years or greater receiving isolated coronary artery bypass grafting from September 2001 to November 2010 were reviewed. There were 33 male and 5 female patients, aging from 80 to 87 years with a mean of (82.6 ± 1.2) years. Twelve patients underwent conventional (on-pump) CABG and 26 patients underwent off-pump CABG. The number of bypass grafts was 1 to 5 (mean 2.5 ± 1.1). Left internal mammary artery was used in 37 (97.3%) patients.</p><p><b>RESULTS</b>The perioperative mortality was 2.6% (1/38). Postoperative complications included stroke (4 cases), respiratory infection (1 case). The atrial arrhythmias occurred in 25 patients. Intensive care unit and hospital length of stay lasted (3.8 ± 1.4) days and (15 ± 6) days, respectively. Totally 38 patients were followed up for 4 to 70 months. Six patients died during the follow-up period. The 92.6% patients recovered without any cardiac events.</p><p><b>CONCLUSIONS</b>Isolated CABG can be performed safely with acceptable postoperative morbidity and mortality in octogenarians. Appropriate surgical strategy and intensive perioperative treatment must be enhanced in octogenarians who underwent CABG.</p>

Robotically assisted coronary artery bypass grafting on beating heart / 中华外科杂志

<p><b>OBJECTIVES</b>To analyze the safety and efficiency of robotically assisted coronary artery bypass grafting (RACABG) on beating heart using da Vinci S system.</p><p><b>METHODS</b>From January 2007 to March 2011, 105 patients underwent RACABG on beating heart through minithoracotomy. There were 77 male and 28 female patients, aged from 33 to 77 years with a mean of (59 ± 10) years. After establishment of single left lung ventilation, the 3 trocars of da Vinci system were inserted into the left hemithorax, and robotic system was used to harvest the left internal mammary artery (LIMA) and/or right internal mammary artery (RIMA) from the subclavian vein to the internal mammary artery (IMA) bifurcation with skeletonized technique. After positioning the stabilizer, the LIMA was anastomosed manually to the left anterior descending or diagonal branch sequentially on beating heart through left minithoracotomy. The graft flow was evaluated by the Doppler flow meter after anastomosis was completed, and the graft patency was also evaluated by CT angiography or arteriography after surgery.</p><p><b>RESULTS</b>All patients had successful RACABG on the beating heart, and the mean graft flow was (21 ± 13) ml/min. One patient suffered from cardiac arrest after the first postoperative day, but he recovered soon and CT angiography showed that graft was patent. One patient with preoperative stroke had postoperative pulmonary infection, and was discharged after treatment. After 4 to 5 days, 4 patients received stent placement in right coronary artery or circumflex coronary in distinct hybrid session. There were no deaths or stroke or reintervention. All patients were discharged without complications and followed up. CTA or angiography revealed patent grafts in all patients, and the mean time of follow-up was (30 ± 12) months.</p><p><b>CONCLUSIONS</b>Robotically assisted coronary artery bypass grafting on beating heart can be performed safely using da Vinci S system. It is a new advanced approach of revascularization not only for patients with single vessel but with multi-vessel lesions as well.</p>

Analysis on the risk factors of intracardial thrombus after prosthetic valve replacement: a 1-year follow-up study / 中华外科杂志

<p><b>OBJECTIVE</b>To analysis the risk factors predicting intracardial thrombus after prosthetic valve replacement.</p><p><b>METHODS</b>The clinical data of 29 cases from January 2005 to April 2009 with intracardial thrombus after prosthetic valve replacement during a 1-year follow-up was retrospectively analyzed. There were 11 male and 18 female, aged from 12 to 70 years with a mean of 48 years. The risk factors of intracardial thrombus were examined by univariate and multivariate analysis.</p><p><b>RESULTS</b>Univariate analysis found that bioprosthetic valve replacement, anticoagulation using aspirin, valve replacement at mitral position, atrial fibrillation, preoperative and postoperative internal diameter of left atrium, postoperative fibrinogen were predict factors of intracardial thrombus after prosthetic valve replacement (P < 0.05). Logistic regression analysis showed valve replacement at mitral position (OR = 9.815, P < 0.05), atrial fibrillation (OR = 5.267, P < 0.05), preoperative internal diameter of left atrium (OR = 4.529, P < 0.05) were significant risk factors of intracardial thrombus after prosthetic valve replacement.</p><p><b>CONCLUSIONS</b>Valve replacement at mitral position, atrial fibrillation, and preoperative internal diameter of left atrium are the correlated risk factors of intracardial thrombus after prosthetic valve replacement. Anticoagulation after prosthetic valve (especially bioprosthetic valve) replacement should be standardized to prevent intracardial thrombus formation.</p>

Studies on separation, appraisal and the biological activity of 5-HMF in Cornus officinalis / 中国中药杂志

<p><b>OBJECTIVE</b>To develop the mechanism of improving protection function of prepared Cornus officinalis for liver and kidney and the biological activity of 5-hydroxymethylfurfural (5-HMF).</p><p><b>METHOD</b>Pharmacological and chemical studies were used to choose active part. A compound from active part was separated and appraised. To investigate his biological functions, pharmacological experiment was actualized.</p><p><b>RESULT</b>A component was separated and identified. His is 5-HMF. 5-HMF can protect human vein epidermal cell against H2O2 and glucose and inprove acute liver injury in mice.</p><p><b>CONCLUSION</b>5-HMF is the active component in prepared Cornus officinalis and substance basis for protecting liver and kidney.</p>

Expressions of CL16/CR6 and CL12/CR4 in first-trimester human trophoblast cells / 中华妇产科杂志

Objective To investigate the transcription and protein expressions of chemokines CL16, CL12 and their receptors CR6, CR4 in first-trimester human cytotrophoblast cells and human choriocarcinoma cell line JAR. Methods Transcriptions of CR6, CL16, CR4, CL12 in purified first-trimester human trophoblast cells and JAR line were assessed by semi-quantitative RT-PCR, and protein expressions of CR6, CL16, CR4, CL12 were analyzed in primary cultured villous cytotrophoblasts (VCT), extravillous cytotrophoblasts (EVCT), JAR line and placentas by immunostaining. Results CR6 and CR4 were highly transcribed in primary cultured trophoblast cells with mRNA relative level of 1.12?0.25 and 1.08?0.11 respectively, and their ligands CL16 and CL12 were transcribed moderately with mRNA relative level of 0.89?0.11 and 0.78?0.10 respectively. It was demonstrated that CL16, CL12, CR6 and CR4 were expressed in primary cultured VCT, EVCT, JAR line and placentas by immunostaining. Conclusion The co-expression of CL16/CR6 and CL12/CR4 in trophoblast cells may play a role in the proliferation and differentiation of first-trimester trophoblast cells in a manner of autocrine.

Transcription of chemokine receptors in villi and trophoblasts of human first trimes-ter gestation / 中国免疫学杂志

Objective: To investigate the mRNA expression of chemokine receptors in human villi and trophoblasts of first trimester gestation . Methods: The authors first obtained villous tissues from fifteen women who had undergone selective termination at 5 - 10 weeks of normal gestation. Total RNA was then extracted, using the TRIzol reagent, from villous tissues or Percoll-gradient purified trophoblasts. Consequently, the expressions of chemokine receptors in villous tissues and trophoblasts were investigated by way of semi-quantitative reverse transcriptase-polymerase chain reaction.Results: The chemokine receptors, CXCR4 and CXCR6, were highly expressed in each villous tissue, while the CCR6, CCR7, XCR1 and CX3CR1 were moderately expressed in villi. The chemokine receptors, CCR1- CCR5, CCR8 - CCR10, CXCR1 -CXCR3, were expressed only in some villous samples, while no CXCR5 mRNA was found in any villous tissue. The authors also found that the freshly isolated and Percoll-purified trophoblasts expressed CCR1, CCR3 - CCR5, CCR8 - CCR9, CXCR1 - CXCR4, CXCR6, XCR1 and CX3CR1 mRNA. Conclusion: A variety of chemokine receptors were expressed in villous tissues and trophoblasts of human first trimester gestation, hence, these receptors may play an important biological role at the materno-fetal interface in normal human pregnancy.