Inhibitory effect of curcumin on proliferation and expression of VEGF and NF-κB p65 of HRCECs induced by high glucose / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the effects of different concentrations of curcumin on the proliferation and expression of VEGF and NF-κB p65 of human retinal capillary endothelial cells(HRCECs)induced by high glucose <i>in vitro</i>.<p>METHODS: The hyperglycemia model of HRCECs in vitro was established by simulating diabetic environment with high glucose medium. The cultured cells were divided into normal control group, high glucose control group, high glucose + 20, 40 and 80μmol/L curcumin groups. The proliferation of HRCECs was detected by CCK-8 assay, and the expression of VEGF and NF-κB p65 was detected by Western-blot and immunocytochemistry.<p>RESULTS: The results of CCK-8 assay showed that high glucose promoted the proliferation of HRCECs significantly compared with the normal control group(<i>P</i><0.01). Curcumin at different concentrations could inhibit the proliferation of cells significantly in a concentration-dependent and time-dependent manner compared with the high glucose control group after being treated with curcumin at different concentrations for 12, 24 and 48h(<i>P</i><0.01). The results of Western-blot showed that compared with the normal control group, the expression of VEGF-A and NF-κB p65 in the high glucose control group was increased significantly(<i>P</i><0.01). Compared with the high glucose control group, the expression of VEGF-A and NF-κB p65 decreased significantly after being treated with curcumin at different concentrations for 12, 24 and 48h, and positively correlated with concentration and time(<i>P</i><0.01). The results of immunocytochemistry showed that the expression of VEGF in the high glucose control group was significantly higher than that in the normal control group(<i>P</i><0.01). After 24h of treatment with curcumin,the expression of VEGF was gradually decreased compared with the high glucose control group(<i>P</i><0.01). There were significant differences in pairwise comparison between each group(<i>P</i><0.01).<p>CONCLUSION: Curcumin can inhibit the proliferation and the expression of VEGF and NF-κB p65 of HRCECs induced by high glucose in a concentration-dependent and time-dependent manner, which may be related to its down-regulation of the expression of VEGF and NF-κB p65.

Colistin induced peripheral neurotoxicity involves mitochondrial dysfunction and oxidative stress in mice.

Polymyxin is a critical antibiotic against the infection caused by multidrug-resistant gram-negative bacteria. Neurotoxicity is one of main dose-limiting factors. The present study aimed to investigate the underlying molecular mechanism on colistin induced peripheral neurotoxicity using a mouse model. Forty mice were divided into control, colistin 1-, 3- and 7-day groups, the mice were intravenously injected with saline or colistin (sulfate) at the dose of 15 mg/kg/day for 1, 3 and 7 days, respectively. The results showed that, colistin treatment for 7 days markedly resulted in the demyelination, axonal degeneration and mitochondria swelling in the mice's sciatic tissues. Colistin treatment induces oxidative stress as well as the increases of mitochondrial permeability transition, decreases of membrane potential (ΔΨm) and activities of mitochondrial respiratory chain in the mice's sciatic nerve tissues. Furthermore, in the colistin-7 day group, adenosine-triphosphate (ATP) level Na+/K+-ATPase activity decreased to 75.2% (p < 0.01) and 80.1% (p < 0.01), respectively. Meanwhile, colistin treatment down-regulates the expression of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) mRNAs and up-regulates the expression of Bax and caspase-3 mRNAs. Our results reveal that colistin induced sciatic nerves damage involves oxidative stress, mitochondrial dysfunction and the inhibition of Akt/mTOR pathway.

Research Progress in Animal Models of IBS-D Disease Combined with Liver Stagnation and Spleen Deficiency / 中国中医药信息杂志

At present, TCM treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) is based on the combination of disease differentiation and syndrome differentiation. Therefore, the establishment of IBS-D of liver stagnation and spleen deficiency syndrome combined with animal model as a combination of traditional Chinese and Western medicine innovation theory has become increasingly concerned about, and gradually become a new direction for the development of TCM experimental animal model. This article reviewed the research progress in IBS-D liver and spleen deficiency syndrome in recent years, discussed the establishment of IBS-D liver stagnation and spleen deficiency animal model and research ideas for the treatment of IBS-D, and provided references for mechanism research of TCM treatment for IBS-D and research and development of new medicine.

A single amino acid substitution alter antigenicity of Glycosylated protein 4 of HP-PRRSV.

BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is an important pig endemic disease in pork-producing countries worldwide. The etiology, porcine reproductive and respiratory syndrome virus (PRRSV), is characterized by fast antigen variability. Glycosylated protein 4 (GP4) is a minor protein in PRRSV virion, but contributes to induce protective immune responses. However, the antigenic characterization of PRRSV GP4 and the role of the mutations in this protein in PRRSV evolution are not clear. METHODS: Peptides chip scanning and peptide based ELISA was used to analyze the antigenic characterization of HP-PRRSV GP4. A total of 142 peptides printed on a chip were used to reveal the antigen reaction characteristics of the HP-PRRSV. The reactions of these peptides with HP-PRRSV-specific pig serum were scanned and quantified using the software PepSlide® Analyzer by fluorescence intensity. The active reaction regions (AR) were identified based on the scanning results and then the amino acids (aa) sequences of AR(s) is aligned among PRRSV strains for further identify the key aa site(s) impact the antigenicity of the protein. Peptide based ELISA is then reacted with PRRSV positive sera derived from pig inoculated with different PRRSV strains for further analysis the role of specific amino acid in AR. RESULTS: The intensity plot was used to show the reactions of the peptides with PRRSV serum and it showed that enormously different response happened to various parts of GP4. The highest reaction intensity value reached 6401.5 against one peptide with the sequence DIKTNTTAASDFVVL. An AR from S29 to G56 was identified. Sequence alignment revealed various mutations in site 43 and possibly played an important role in this AR. Peptides ELISA reaction with sera from pigs inoculated with different PRRSV strain revealed that the change of aa in site 43 reduced the reaction of the peptide with PRRSV positive sera derived from pigs inoculated with the peptide related PRRSV strains. CONCLUSION: In this study, one AR covering S29 to G56 was identified in GP4. The aa in site 43 play an important role in determining the antigenic character of GP4. The continual mutations (S → G → D → N) occurred in this site alter the antigenicity of PRRSV GP4.

Tissue distribution of galactosyl daphnoretin liposomes in rats / 中国中药杂志

To study the tissue distribution of galactosyl daphnoretin liposomes in rats. At the dose of 10 mg•kg⁻¹, daphnoretin solution, daphnoretin liposomes, and galactosyl daphnoretin liposomes were administered to healthy SD rats via tail vein injection. The blood and tissue of heart, liver, spleen, lung, kidney, stomach, small intestine, brain and thymus were collected at 5, 15, 30, 45, 60, 120, 240, 360 min after administration. The concentrations of daphnoretin in plasma and tissue samples were determined by HPLC. The results showed that galactosyl daphnoretin liposomes group had the highest concentration of daphnoretin in liver of unit weight at different time points; and at all of the time points, the target index DTI values of galactosyl daphnoretin liposomes to liver were greater than that of daphnoretin liposomes. Compared with daphnoretin solution, the AUC0-6 and Cmax of galactosyl daphnoretin liposomes in liver were 2.23, 5.22 times, respectively. This indicated that galactosyl daphnoretin liposomes can be concentrated at liver, with a significant liver targeting effect.

Effects of Lonicera Japonica flavone on immunomodulation in mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study immunomodulating activity of Lonicera Japonica flavone by investigating immune enzymatic activity of serum and antoxidized activity of lymphoid organs in mice.</p><p><b>METHODS</b>Fifty KM mice were randomly divided into control group, model group, low dose group, middle dose group and high dose group(n = 10), respectively. And low dose group, middle dose group and high dose group were given Lonicera Japonica flavone with 100 mg/kg, 200 mg/kg and 400 mg/kg every day, respectively, while control group and model group were administered with NS. After continuously giving drug 7 weeks, other groups were injected with Dexamethasome (Dex: 25 mg /kg) for 3 days by subcutaneous injection, but the control group were treated with NS. And after giving Lonicera Japonica flavone 1 week simultaneously, organ indexes , the activity of acid phosphatase (ACP), alkaline phosphatase (AKP) and lysozyme (LSZ) in serum , and the content of monoamine oxidase (MAO), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD) and malondialdehyde (MDA) in lymphoid organs in mice were tested, respectively.</p><p><b>RESULTS</b>Lonicera Japonica flavone could significantly improve the organ indexes, and significantly improve the activity of ACP, AKP and LSZ in serum, and significantly improve the contents of T-AOC and SOD, but reduce that of MAO and MDA in lymphoid organs in immunosuppressed mice.</p><p><b>CONCLUSION</b>Ionicera Japonica flavone can significantly improve the activity of immune enzyme in serum and the antioxidized activity of lymphoid organs in mice. It suggests that Ionicera Japonica flavone has a good immunomodulatory effects.</p>

Time trends and age-related characteristics of cardio-cerebrovascular deaths in Hunan / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the time trends and age-related characteristics of mortality and disease burden for cardiocerebrovascular diseases (CVD) in Hunan, China during three periods (1973-1975, 1990-1992 and 2004-2005).</p><p><b>METHODS</b>The cardiocerebrovascular death data of Hunan residents were collected by three national retrospective sample surveys of death. Cause-specific mortality, proportion, years of potential life lost (YPLL) and associated indicators were identified in the population of Hunan in above mentioned three periods. Time trends of age-specific mortality rate were assessed by fitting curvilinear regression lines and the increase rates of mortality with age were analyzed in each period.</p><p><b>RESULTS</b>The standard all-cause mortality of residents in Hunan decreased (chi2 = 189.947, P < 0.001, chi2 = 54.201, P < 0.001; chi2 = 27,396.898, P < 0.001) while the standard mortality for CVD increased (chi2 = 54.201, P < 0.001; chi2 = 27,396.898, P < 0.001) from 1973 to 2005. The age-specific mortality rate for CVD increased with age in all three periods, especially for citizens older than 60 years. There were age stages in each period in which the mortality increase rate was the fastest (10-14 and 15-19 years old in 1973-1975; 10-14, 15-19 and over 80 years old in 1990-1992; 15-19 and over 80 years old in 2004-2005). Exponential regression function (y = b0e(b1x)) can be used for the proper description of age-specific mortality change. The ratio of YPLL for CVD in all death causes showed increase trend (chi2 = 275,630.407, P < 0.001). YPLL rate (YPLLs per 1000) in 1973-1975 was higher than those in 1990-1992 and 2004-2005. YPLL rate was positively correlated with mortality in all periods.</p><p><b>CONCLUSIONS</b>The mortality for CVD increased with time and aging. People older than 60 years were threatened by CVD mostly. Mortality trend analysis also found higher CVD deaths in people age 15-19 in Hunan residents.</p>