Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell / 中华肿瘤杂志

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Analysis of the influence of different regimens of highly active antiretroviral therapy on maternal and infant outcomes in HIV-infected pregnant women / 中国实用妇科与产科杂志

OBJECTIVE: To compare the maternal and infant outcomes of pregnant women infected with human immunodeficiency virus(HIV)treated with different regimens of highly active antiretroviral therapy(HAART).METHODS: For pregnant women infected with the human immunodeficiency virus(HIV)who received antiviral therapy and delivered in the Eighth Peple's Hospital of Guangzhu between May 2015 and June 2018,they will be grouped according to different treatment options. The pregnant women's body weight,CD4+T lymphocytes,white blood cells,hemoglobin,serum albumin,neonatal body weight and adverse pregnancy outcomes were compared and analyzed.RESULTS:(1)There was no significantly statistical difference between the two groups of pregnant women in terms of body weight,white blood cells,hemoglobin or serum albumin(P>0.05).(2)The changes of CD4+T lymphocytes in the two groups of pregnant women before and after treatment were statistically different(P0.05).(4)There was no significantly statistical difference in the incidence of premature birth,premature rupture of fetal membrane,low birth weight,low amniotic fluid,fetal malformation or neonatal asphyxia between the two groups(P>0.05).Until December 2018,there were no positive reports of HIVRNA and HIV antibody detection in two groups of infants.CONCLUSION: The two HAART schemes have no significant difference in the influence on nutritional status,immune status or maternal and infant outcomes of HIV-infected pregnant women,and they are both effective and feasible,and vertical transmission of HIV from mother to child can be blocked.

Electrochemical Immunosensor for Microcystin-LR Detection Based on Nano-composite Material Immobilization and Enzymatic Amplification / 分析化学

A competitive electrochemical immunosensor based on the nano-composite material immobilization and enzymatic amplification was designed for detection of microcystin-LR. Gold nanoparticles/carboxylated multi-walled carbon nanotubes (AuNPs/c-MWCNTs) composite film, which formed by electrodepositing of AuNPs on the C-MWCNTs modified glassy carbon electrode,was used for the immobilization of the antibody of microcystin-LR (anti-MCLR). Horseradish peroxidase (HRP) was introduced onto the nanocomposite interface by HRP blocked sensing interface and specific capture of antibody with target. It could be employed to catalyze the reduction of H2O2, and to block the possible remaining active sites as well. A competitive immunoreaction between antigen and MCLR-HRP was used for target analysis. In the presence of H2O2and hydroquinone (HQ),MCLR could be indirectly detected with differential pulse voltammetry (DPV) method by determining the reduction current of HQ. Under the optimal conditions, the proposed immunosensor exhibited wide linear ranges in the concentration ranges of 0.1-100.0 μg/L, with a detection limit of 0.038 μg/L (S/N = 3,n=8). The immunosensor showed good specificity, stability and sensitivity. It was used to determine MCLR in real water samples with the recoveries of 72.9%-117.3%.

Protective effect of sodium ferulate magnetic nanoparticle in septic kidney injury rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the renal protective effect of sodium ferulate magnetic nanoparticle targeting therapy in septic rats receives norepinephrine treatment.</p><p><b>METHODS</b>First we constructed sodium ferulate magnetic nanoparticle, Wistar male rats were randomly divided into 4 groups (n = 6): control group, septic group, norepinephrine treatment group (NE treatment group) and NE plus sodium ferulate magnetic nanoparticle treatment group (NE + SF group), septic rat model was reproduced by intravenous injection of lipolysaccharide (IPS) in rats in NE treatment group norepinephrine were used to elevate the blood pressure of septic rats, in NE + SF group sodium ferulate magnetic nanoparticle was injected via tail vein, magnetic field was placed near renal region. Urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), renal tissue concentration of malonaldehyde (MDA), superoxide dismutase (SOD), and serum concentration of blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured 3 hours after treatment.</p><p><b>RESULTS</b>After injected LPS via tail vein, systolic blood pressure, pH value, PaO2 and PaCO2 of arterial blood of septic rats decreased significantly. Systolic blood pressure, pH value, PaO2 and PaCO2 of arterial blood returned to baseline approximately after norepinephrine treatment, sodium ferulate magnetic nanoparticle targeting therapy did not change hemodynamic effects of norepinephrine. Compared with control group, urine NAG, KIM-1 and NGAL of sepsis group were increased significantly (P < 0.01), after treatment with norepinephrine, urine NAG, KIM-1 and NGAL of NE treatment group were elevated rapidly compared with those of sepsis group (P < 0.01), combined with sodium ferulate magnetic nanoparticles targeting treatment, urine NAG, KIM-1 and NGAL of NE + SF group were decreased significantly compared with those of sepsis group and NE treatment group (P < 0.01). Compared with control group, renal tissue MDA levels of septic rats increased significantly (P < 0.01), NE treatment could notably raise MDA levels compared with those of sepsis group (P < 0.01), renal tissue MDA levels of NE + SF group were decreased significantly compared with those of sepsis group and NE treatment group (P < 0.01). Compared with control group, renal tissue activities of SOD of sepsis group and NE treatment group were decreased significantly (P < 0.01), after targeted treatment with sodium ferulate magnetic nanoparticle, renal tissue SOD activities of NE + SF group increased significantly compared with those of sepsis group and NE treatment group (P < 0.01 vs sepsis group and NE treatment group). Serum BUN, Cr, ALT, AST levels did not significantly change in each groups.</p><p><b>CONCLUSION</b>Sodium ferulate magnetic nanoparticle targeting therapy can effectively decrease urine NAG, KIM-1, NGAL and renal tissue MDA level, increase tissue SOD activity of sepsis group and NE treatment group rats, thus protect renal function of septic rats.</p>

Protective effect of astragalosides on anoxia/reoxygenation injury of hippocampal neuron / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of astragalosides (AST) on the anoxia/reoxygenation (A/R) injured neuron in rat.</p><p><b>METHODS</b>Primary cultured rat's hippocampal neurons were made into A/R model cells. The cell viability was detected by MTT assay and lactate dehydrogenase releasing methods; the activity of superoxide dismutase (SOD), and contents of malondialdehyde (MDA) and nitride oxide (NO) in culture supernate were detected; the apoptosis rate of hippocampal neurons after A/R was measured by flow cytometry with double-staining of Hoechst33258 and AnnexinV-PI; and intracellular calcium ion [Ca2+]i was observed with a cofocal laser-scanning microscope and determined by fluorescent probe Fluo-3/AM.</p><p><b>RESULTS</b>AST enhanced the cell viability of neurons after A/R injury, increased SOD activity and decreased the MDA and NO contents in supernate, reduced the A/R-induced apoptosis and decreased the calcium overload in neurons.</p><p><b>CONCLUSION</b>AST has the protective effects on A/R injured neurons, the mechanism is possibly related with its anti-oxidation and calcium overload reducing actions.</p>

Protective effects of Shexiang Xingnaonin on focal cerebral ischemia/reperfusion injury and mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protective effects of Shexiang Xingnaonin (SXN) on focal cerebral ischemia/reperfusion injury and its mechanism.</p><p><b>METHOD</b>Middle cerebral artery occlusion (MCAO) was used to make focal cerebral ischemia/reperfusion model by in travascular nylon filament occlusion. The protective effects of SXN at different doses were evaluated by investigating neurological function score, pathomorphology of brain, the ultrastructure of neuron, expression of tumor necrosis factor-alpha, thrombogenesis in vitro, platelet aggregation and lysing effect of blood clot in vitro.</p><p><b>RESULT</b>Compared with model group, SXN (0.08, 0.16 g x kg(-1)) could decrease the neurological score, improve pathomorphology and neuron ultrastructure of brain, inhibit the expression of TNF-alpha, decrease the length, wet weight and dry weight of thromb and inhibit platelet aggregation. And SXN (0.16, 0.32 g x L(-1)) could dissolve blood clot in vitro.</p><p><b>CONCLUSION</b>SXN has protective effects on focal cerebral ischemia/reperfusion injury. The role of inhibit the expression of TNF-alpha, inhibit thrombogenesis and platelet aggregation might contribute to its neuroprotective effects.</p>

Effects of AST and ASI on metabolism of free radical in senescent rats treated by HC / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of Astragaloside (AST) and Astragalus Saponin I (ASI) on metabolism of free radical and immune function in senescent rats treated by HC.</p><p><b>METHOD</b>Hydrocorisone (HC) was used to estabilsh the aging model in rats. The content of molondialdehyde (MDA), glutathoine (GSH) and oxidized glutathoine (GSSG) in liver and brain was detected according to kit. The activity of Mn superoride dismulase (Mn-SOD) and catalase (CAT) was also surveyed by kit. Concanavalin (ConA) was used to detect the proliferation and interleukin-2 (IL-2) production of splenocytes.</p><p><b>RESULT</b>Compared with HC control, AST and ASI could decrease the content of MDA, GSH and GSSG in liver and brain, increase the activity of Mn-SOD and CAT, and promote the proliferation and interleukin-2 (IL-2) activity of splenocytes.</p><p><b>CONCLUSION</b>AST and ASI could delay the aging effect in rats treated by HC, and its mechanism maybe the antioxidant and regulating immunity.</p>

Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A bioactive compound from Paecilomyces tenuipes (BCPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress (CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.</p><p><b>METHODS</b>The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21. Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone (CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.</p><p><b>RESULTS</b>Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.</p><p><b>CONCLUSIONS</b>BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.</p>