Objective:To explore the enhanced sensitization to chemotherapeutic agent paclitaxel-induced apoptotic effect on p185-overexpressing human malignant breast cancer cell lines SKBr3 by anti-p185c-erbB-2/neu engineered antibody treatment and to study its emerging mechanism.Methods:The proliferative inhibitory effect was assessed by MTS assay; Cells stained with AnnexinV-FITC and PI were used to qualify the apoptotic cell number by FACS(Fluorescence-activated cell sorting) analysis; Phosphorylation of Ser473 AKt and p65 NF-?B subunit were determined by Western blot; NF-?B-DNA binding activity was demonstrated by EMSA(Electrophoretic mobility shift assay).Results:Anti-p185c-erbB-2/neu engineered antibody rendered SKBr3 cells more susceptible to paclitaxel-induced proliferative inhibition, which further attributed to apoptotic induction; Furthermore, combination of the engineered antibody and paclitaxel also showed effective suppression of AKt/NF-?B pathway in SKBr3 cells.Conclusion:The aggressiveness of AKt/NF-?B pathway was partly attributed to its resistance to paclitaxel-induced apoptosis. Anti-p185c-erbB-2/neu engineered antibody plus paclitaxel combination rendered p185-overexpressing human malignant breast cancer cells SKBr3 more susceptible to paclitaxel-induced apoptosis by efficient suppression of AKt/NF-?B pathway.

Objective To investigate the effect of an anti-HER-2 engineered antibody,chA21,on the expression of MMP-2 and TIMP-2 in human ovarian cancer SKOV3 cells that highly express HER-2.Methods After exposure to chA21 at concentrations of 6 mg/L and 12 mg/L for 36 hours,respectively,the expression of MMP-2 and TIMP-2 proteins was detected by immunocyctochemistry.SKOV3 cells were inoculated into nude mice to establish animal models.The mice were respectively administered with normal saline and chA21(30 mg/kg) via injection twice a week for 6 consecutive weeks,and then were killed after 44 days' administration of the drugs.Immnohistochemical staining of MMP-2 and TIMP-2 was observed on tissue microarray sections.Results After exposed to chA21,TIMP-2 protein was increased(P

Aim To explore the effects of anti-HER-2 chimeric antibody chA 21 on proliferation and apoptosis of SKBR3 cells.Methods MTT colorometric assay,HE staining,transmission electron microscopy,flow cytometry,and TUNEL were used to study the proliferation inhibition and apoptosis induction of SKBR3 cells by chA 21 in vitro.Results Proliferative inhibition rates and apoptotic index of SKBR3 cells were increased in a dose and time dependent manner after exposure to chA21(0.2～5.4 mg?L~(-1)).Conclusion chA 21 could remarkably inhibit proliferation of SKBR3 cells in vitro and apoptosis induction may be one of its main mechanisms.

Objective To study the anti-tumor effect of anti-HER-2 engineering antibodies chA21 and Herceptin on nude mice xenografts of human ovarian cancer SKOV3 cells and explore its mechanism.Methods An animal model with human ovarian cancer SKOV3 cells involved in nude mice was established and the mice were randomized into 3 groups: normal saline(NS),chA21 and Herceptin.The mice were respectively administrated with Herceptin(30mg/kg) and chA21(30mg/kg) via caudal vein injection twice a week for consecutive 6 weeks,and then were killed after 44 days adminstration of the drugs.The volumes of the xenografts were measured twice a week.The tumor weight and inhibition ratio were measured after mice were killed.Ki67 and NF?B expression in the three groups was quantificationally analyzed by immunohistochemistry on tissue microarray sections combined with a micro-image analysing system.Results The growth of xenografts of human ovarian cancer SKOV3 cells in nude mice was significantly inhibited by either Herceptin or chA21. Both Ki-67 labeling indices and NF?B levels in chA21 and Herceptin groups were lower than those in the control(P

Objective To investigate the instructive role and clinical effect of invasive intracranial pressure monitoring in treating bilateral posttraumatic acute diffuse brain swelling(PADBS).Methods A total of 52 consecutive patients with bilateral PADBS managed under invasive intracranial pressure monitoring between October 2009 and December 2010 were enrolled as the study group.Another 53 patients with bilateral PADBS managed with non-intracranial pressure monitoring from February 2007 to September 2009 were set as the control group.The clinical outcomes of the two groups were compared.Results The ratios of good recovery[Glasgow Outcome Scale(GOS)=5 points]and severe disability(GOS=3 points)were 59.6％(31/52)and 11.5％(6/52)respectively in the study group,but 35.9％(19/53)and 28.3％(15/53)respectively in the control group(P＜0.05).The death rates of the study and control groups were 5.8％(3/52)and 9.4％(5/53)respectively(P＞0.05),and the average hospital stay was(34.35±17.50)days and(42.43±22.17)days respectively(P＜0.05).Conclusion Durative monitoring of invasive intracranial pressure in treatment of bilateral PADBS can improve prognosis,shorten hospital stay and therefore is worthy of clinical application.

The neurovascular unit (NVU) is a dynamic functional module composed of neurons,microglia,blood-brain barrier (BBB) and the extracellular matrix that maintains the integrity of brain tissues.The chief members of NVU are one of the structural bases of the development of nervous system diseases.And they are involved in the pathological process of depression.The NVU instability of depression is characterized by the uncoupling of nerve and blood vessels,the increase of BBB permeability and the inflammatory response.Traditional Chinese medicine (TCM) has many advantages in the treatment of depression,and the effect of Kai-Xin Jie-Yu (KXJY) decoction in treating depression is remarkable.The purpose of this study was to explain the effect of KXJY decoction on NVU in terms of the functional connectivity of brain white matter,the protection of neurons and glial cells,the protection of vascular endothelial cells,the repair of BBB and the reduction of inflammation.It provided a new theoretical basis and method for the treatment of depression in TCM.

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.