It is generally considered that various regulatory activities between genes are contained in the gene expression datasets. Therefore, the underlying gene regulatory relationship and the biologically useful information can be found by modeling the gene regulatory network from the gene expression data. In our study, two unsupervised matrix factorization methods, independent component analysis (ICA) and nonnegative matrix factorization (NMF), were proposed to identify significant genes and model the regulatory network using the microarray gene expression data of Alzheimer's disease (AD). By bio-molecular analyzing of the pathways, the differences between ICA and NMF have been explored and the fact, which the inflammatory reaction is one of the main pathological mechanisms of AD, is also emphasized. It was demonstrated that our study gave a novel and valuable method for the research of early detection and pathological mechanism, biomarkers' findings of AD.
Algorithms ; Alzheimer Disease ; genetics ; Gene Expression Profiling ; methods ; Humans

Objective To reveal the mechanism of Yuxuan granule(YXG) in treating pharyngitis from anti-inflammatory,expectorant,and antibacterial actions.Methods Xylene-induced ear edema and cotton pellet induced granuloma mice models were adopted to observe the anti-inflammatory effects of YXG Phenol red secretion in mice test was adopted to observe the expectorant activity of YXG Five bacteria by tube dilution method was adopted to observe antimicrobial action of YXG Besides,the changes of routine indexes in blood and tumor necrosis factor (TNF),interleukin-1 (IL-1) in serum were measured in acute pharyngitis models.Results YXG has shown a dose-dependent of its anti-inflammatory action.In the test of xylene induced mice ear swelling and cotton ball induced granuloma,the swelling degree of the control group,positive control groupand YXG high (6.14g/kg),medium (3.07g/kg) and low (1.53g/kg) concentration group were (9.00± 1.50) mg,(3.50±0.10)mg,(4.25±1.08)mg,(5.54±0.97)mg,(8.05±0.08)mg and (1.22±1.50)mg,(0.50±0.10)ag,(0.45± 0.08) mg,(0.75± 0.97) mg,(0.70 ± 0.08) mg respectively.YXG also had obviously expectorant effect to the golden staphylocoecus ameus,hemolytic streptococcus,streptococcus pneumoniae,salmonella typhi and corynebacterium diphtheriae,with the minimum inhibition concentration of 55,100,68 and 35 mg/ml respectively; YXG also reduced leukocyte count [percentage of leukocyte was (9.88± 1.22) × 109/L,(7.50± 1.58) ×109/L,(6.02± 1.05) × 109/L,(8.38± 1.13) × 109/L,(8.75 ± 1.08) × 109/L in the five groups respectively],neutrophils [the value was (35.62±5.00)×109/L,(28.49±3.40)×109/L,(28.89±5.22)× 109/L,(29.34±4.83)×109/L,(33.43 ± 4.27) × 109/L in the five groups respectively],lymphocytes [the value was (70.72± 5.04) ％,(67.89 ±4.37)％,(60.14±3.88)％,(65.38±4.45)％,(65.65±4.28)％ in the five groups respectively],TNF in blood serum [the value was (90.25±2.29)ng/ml,(80.23 ± 0.60) ng/ml,(76.83±0.33)ng/ml,(78.00 ± 0.34) ng/ml,(80.52±1.14)ng/ml in the five groups respectively] and IL-1 [the value was (222.06±50.22)pg/ml,(149.55±50.02)pg/ml,(130.37 ± 30.61)pg/ml,(158.68 ± 40.00)pg/ml,(178.76 ± 39.26)pg/ml in the five groups respectively] in the acute pharyngitis rat.Conclusion Through the anti-inflammatory,expectorant,antimicrobial activity and reducing levels of TNF,IL-1 YXG achieves the goal of treating pharyngitis.

Despite the important properties of GPCRs as drug targets,improving the subtype selectivity and efficiency of new drugs targeting at GPCRs is a predominant challenge.The study of GPCRs allosterism shows there exist great complexity and diversity in allosterism and allosteric sites,and it also provides a new opportunity for exploring new drugs with subtype selectivity and efficiency.This review summaries the development of GPCRs allosterism in recent years and shows GPCRs allosterism and its biological significance.

Objective To investigate the effect of caffeic acid phenethyl ester (CAPE) on the growth of human colorectal carcinoma cell line HCT116 transplanted subcutaneously in nude mice. Methods Nude mouse model of human colorectal carcinoma by subcutaneous transplantation of HCT116 cell line was reproduced. A total of 20 mice were divided into 2 groups: control group and CAPE group (oral administration of CAPE at 5mg/mice/d). The growth of the subcutaneously transplanted tumor and changes in mouse body weight in each group after treatment were observed on 7, 14, 21 and 28d. Histopathological examination of xenograft, heart, liver, lung, kidney and intestine of nude mice was also conducted. Apoptosis index was detected by terminal dUTP nick end labeling (TUNEL) technique. Results CAPE had significantly inhibitory effect on growth of the transplanted xenograft in vivo. Tumor volume and tumor weight were decreased (P

OBJECTIVE:To observe the effects of Paclitaxel,Cisplatin combined with Recombinant human (Rh) endostatin on the efficacy and related indexes of patients with non-small cell lung cancer(NSCLC). METHODS:78 patients with Ⅲb or ⅣNSCLC were randomly divided into control group(39 cases)and observation group(39 cases). Control group received Paclitaxel injection 135-175 mg/m2,d1,intravenous infusion,once a day+Cisplatin injection 25 mg/m2,3 times a day,d1-3,intravenous infu-sion. Observation group additionally received Rh endostatin injection 15 mg/m2,adding into 500 ml 0.9% Sodium chloride injec-tion by slow intravenous infusion 3-4 h,d1-14,then stopped for 7 d. 21 d was regarded as 1 treatment course,it lasted 6 courses. Clinical efficacy,programmed death ligand-1(PD-L1)level,quality of life(QOL)score before and after treatment,and the inci-dence of adverse reactions in 2 groups were observed. RESULTS:All patients completed 2 courses of chemotherapy. There were 3 patients in observation group and 4 patients in control group quitted the study with uncompleted 6 weeks of chemotherapy due to in-tolerance or adverse reactions. The remission rate in observation group was significantly higher than control group,with statistical significance (P<0.05). Before treatment,there were no significant differences in PD-L1 level and QOL score in 2 groups (P>0.05). After treatment,PD-L1 level and QOL score in 2 groups were significantly lower than before,and observation group was lower than control group,with statistical significance (P<0.05). And there was no significant difference in the incidence of ad-verse reactions in 2 groups (P>0.05). CONCLUSIONS:Paclitaxel,Cisplatin combined with Rh endostatin can improve the short-term efficacy of patients with NSCLC,inhibit PD-L1 expression,improve QOL,and do not increase the incidence of adverse reactions.

Objective To investigate the effects of bone mesenchymal stem cell (BMSC) transplantation on neuronal nuclei (NeuN) and neurogenin 1 (Ngnl) in focal cerebral ischemic rats.Methods A total of 64 healthy adult male Sprague-Dawley rats were randomly divided into normal (N) + phosphate-buffered solution (PBS),middle cerebral occlusion (MCAO)+ PBS,N + BMSC and MCAO + BMSC groups (n =16 in each group).A rat model was induced by the intraluminal suture method.BMSC was cultured in vitro.At 24 h after modeling,brain transplantation was conducted.Magnetic resonance imaging (MRI) was used to detect infarct volume in vivo.NeuN/DAP,Ngnl/DAPIimmunofluorescence double-labeling and Western blot were used to detect the expression of NeuN and Ngnl around ischemic brain tissue.Results On day 14 after transplantation,the T1-and T2-weighted imaging revealed that the cerebral cortex and striatum had abnormal signal areas in the rats of the MCAO group.The infarct volume of the MCAO + BMSC group was significantly less than that of the MCAO + PBS group (32.5％ ± 4.2％ vs.47.9％ ± 7.9％ ; P ＜ 0.01).Immunofluorescence doublelabeling assay showed that the numbers of cells of NeuN+/DAPI+ (976.2 ± 87.5/mm2 vs.1 908.3 ±127.8/mm2; P ＜ 0.01) and Ngn1 +/DAPI + (251.6 ± 23.1/rmm2 vs.285.1 ± 25.2/mm2 ; P ＜ 0.01) of the MCAO + PBS group were significantly less than those of the N + PBS group,but those of NeuN+/DAPI +(1 439.9 ± 101.7/mm2; P ＜ 0.01) and Ngn1 +/DAPI + (356.3 ± 35.6/mm2; P ＜ 0.01) of the MCAO + BMSC group were significantly more than the MCAO + PBS group.Western blot analysis showed that the protein expression levels of NeuN (0.69 ±0.06 vs.0.91 ±0.09; P ＜0.01) and Ngn1 (0.53 ±0.05 vs.0.62 ±0.07;P ＜0.01) of the MCAO +PBS group were significantly lower than those of the N +PBS group,but those of NeuN (0.82 ± 0.07; P ＜ 0.01) and Ngn1 (0.77 ± 0.09; P ＜ 0.01) of the MCAO + BMSC group were significantly higher than the MCAO + PBS group.Conclusions BMSC transplantation may promote the expression of NeuN and Ngn1,and alleviate MCAO caused brain injury.

AIM: To clone and express the gene of SLC24A6, which provide the basis to illuminate the relationship between the SLC24A6 and insulin release. METHODS: The gene expression of SLC24A6 was analyzed in the insulinoma and normal pancreatic tissues by RT-PCR. The full-length cDNA sequence was subcloned into pET32a vector, and induced expression and purified in ROSSET (DE3) strain. At the same time, the ORF of SLC24A6 was cloned into green fluorescence protein vector pEGFP-C3 to study the location of SLC24A6 in the mouse insulinoma ?-TC3 cells. RESULTS: The mRNA expression of SLC24A6 in the human insulinoma tissue was significantly higher than that in normal pancreatic tissue. The fusion protein of SLC24A6 was a 80 kD protein and was purified successfully by prokaryotic vector in ROSSET strain. The localization of SLC24A6 in the mouse insulinoma ?-TC3 cells was located in the membrane of the cells. CONCLUSION: SLC24A6 might be related with insulin release. The prokaryotic expression of SLC24A6 provides the basis for the study on biological function and protein structure, and the location of SLC24A6 in the insulinoma cell will throw light on the relationship with insulin release.

Objective To study the effect of morin on LPS induced acute lung injury mouse model and its mechanism .Meth‐ods Thirty male C57B/L mice were randomly divided into control group ,LPS group and LPS+ morin group ,with 10 in each group .5 mg/kg LPS was instilled into the lung from an trachea intubation in LPS group and LPS+morin group .Then the mice in LPS+morin group received an intraperitoneal injection of morin (40 mg/kg) every day for the next 3 d .Others received an equal a‐mount of saline .After 72 h ,the mice were sacrificed .The bronchoalveolar lavage fluid (BALF) was collected and centrifuged;the sediments were stained with Wright‐Giemsa for total cell and neutrophil count and the supernates were prepared for ELISA .The wet and dry weight of lung was weighed to calculate the wet/dry weight ratio .HE staining was performed to examine the pathologi‐cal change of lung .Western blot was used to determined the expression of TLR4 ,IKK and NF‐κB .Results Intratracheal instillation of LPS successfully established ALI model in mouse .LPS caused significant pathological changes including inflammatory cells infil‐tration ,alveolar septa thickness ,hemorrhage and edema .The wet/dry weight ratio ,the total cell count ,neutrophil count ,TNF and IL‐1βlevel in BALF ,and the expression of TLR4 ,NF‐κB ,and IKK were all increased significantly (P<0 .05) ,which were allevia‐ted by intraperitoneal injection of morin .Conclusion Morin can dampen the inflammatory response during LPS induced ALI in mouse ,which is potentially attributed to its inhibitory effect on the activation of NF‐κB .

Objective:To explore the inhibitory effects of gefitinib(epidermal growth factor receptor inhibitor) combined with celecoxib(cyclooxygenase-2 inhibitor) against human lung cancer A549 cells and the possible mechanism.Methods: A549 cells were cultured in RPMI 1640 medium and were divided into 4 groups: normal control group,5 ?mol/L gefitinib group,25 ?mol/L celecoxib group,and 5 ?mol/L gefitinib+25 ?mol/L celecoxib group.The morphological changes of A549 cells were observed under inverted microscope 48 h after treatment;the effects of drugs on growth of A549 Cells were detected by MTT assay;the apoptosis and cell cycles of A549 cells were measured by Annexin V/PI and Hoechst 33258 staining,respectively;and the expression of EGFR protein,COX-2 protein,and EGFR mRNA were determined by immunofluorescence and real-time PCR.Results: Compared with gefitinib and celecoxib groups,many granules and vacuoles were observed in the gefitinib and celecoxib combination group,and cells became round and there was defluxion.Both gefitinib and celecoxib inhibited the growth of A549 cells in a time-and dose-dependent manner.After treatment for 48 h,the inhibitory rate was(58.2?4.6)% in the combination group,which was significantly higher than those of the other two groups.Apoptosis rate in the combination group was also significantly higher than those in the other two groups(33.9% vs 6.0%,8.8%),and the cell proportion in S phase significantly decreased and in G0/G1 phases significantly increased(P

The anti-idiotypic antibodies Specific for anti-HBs were prepared by Immunizing New Zealand white rabbits with anti-HBs according to the method of Kennedy. The serum was first purified through IgG of normal human-Sepharose 4B affinity Column.The anti-idiotypic Specificity of the antibodies obtained was identified with ELISA or RIA inhibition test.The resultshowed that the anti-idiotypic antibodies were directed at the idiotypic determinants on anti-HBs,and no cross reaction between anti-idiotypic antibodies and normal human IgG.