The antidepressant effect of albiflorin based on TSPO and mechanism / 中国药理学通报

Aim To study the antidepressant effects of albiflorin and its relationship with TSPO(translocator protein 18 ku). Methods Mice were divided into eight groups(control group, chronic unpredictable stress group, fluoxetine group, albiflorin low, medium, high dose groups, PK11195 group, PK11195+ albiflorin high dose group)based on the data of the behavioral tests conducted to assess the antidepressant-like effects of albiflorin. After the behavioral tests Western blot and ELISA were conducted to evaluate the TSPO expression, progesterone and allopregnanolone level in hippocampus of mice. Results In the behavioral tests, there were significant differences between the model group and the control group, which indicated that the model was successfully established. The positive drug and albiflorin in different dose groups could reverse the effects of the model group, and PK11195 could reverse the effects of paeoniflorin in high dose group. The results of Western blot and ELISA showed that the TSPO expression, progesterone and allopregnanolone level in the model group significantly decreased. The positive drug and albiflorin groups with different doses could reverse the effects of the model group, and PK11195 could reverse the effects of the high dose group. Conclusions Albiflorin has significant antidepressant and antianxiety effects on CUS mice by TSPO, which provides experimental basis for the further study on the antidepressant effects and mechanism of albiflorin in the future.

Effect of Tianwang Buxin Pills on Behavior, HPA Axis, BDNF Expression and Phosphorylation of GSK3β in Mice with Chronic Unpredictable Stress / 中国实验方剂学杂志

Objective:To investigate the effect of Tianwang Buxin pills on behavior， hypothalamus pituitary adrenal axis （HPA axis）， hippocampal glycogen synthase kinase 3β （GSK3β） phosphorylation and brain-derived neurotrophic factor （BDNF） expression in mice with chronic unpredictable stress， and explore its mechanisms for antidepressant-like action. Method:Totally 60 male ICR mice were randomly divided into normal group， chronic stress model group， fluoxetine hydrochloride group （10 mg·kg-1） and Tianwang Buxin pills high， middle and low dose groups （3.6， 1.8， 0.9 g·kg-1）. The mice were subjected to the chronic unpredictable stress （CUS） protocol for a period of 28 d to induce depressive-like behavior. Then， a sucrose preference test， open-field test and novelty-suppressed feeding test were performed to detect the behavior changes. The blood， adrenal gland and hippocampus of mice were collected. The contents of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The changes of GSK3β phosphorylation and BDNF expression in hippocampus were detected by Western blot， and the adrenal index was then calculated. Result:As compared with the normal group， the sucrose water preference was significantly decreased （P<0.01）， the number of opening activities was significantly reduced （P<0.05）， the feeding latency of novelty inhibition was prolonged （P<0.01）， the serum ACTH and CORT contents were significantly increased （P<0.05，P<0.01）， GSK3β phosphorylation and BDNF expression levels in hippocampus were significantly decreased （P<0.01）， and adrenal index was significantly increased in model group （P<0.01）. As compared with the model group， Tianwang Buxin pills treatment significantly reversed the CUS-induced behavioral abnormalities in depression model mice （P<0.05， P<0.01）， significantly decreased the levels of plasma ACTH and CORT （P<0.01） and adrenal and adrenal gland index （P<0.01）， while increased GSK3β phosphorylation and BDNF expression in hippocampus （P<0.05， P<0.01）， with its effect similar to that of fluoxetine hydrochloride. Conclusion:Tianwang Buxin pills produced antidepressant-like effects in chronic unpredictable stress mice， and its mechanism may be associated with inhibiting HPA axis activity and up-regulating GSK3β phosphorylation and BDNF protein expression in hippocampus.

Effect of different blood pressure control targets within 48 h after hypertensive cerebral hemorrhage on hematoma enlargement and prognosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of different blood pressure control targets on hematoma enlargement and prognosis in patients within 48 h after hypertensive cerebral hemorrhage (HCH).</p><p><b>METHODS</b>Between January, 2013 and July, 2016, 102 patients with HCH were randomized into group A (51 cases) and group B (51 cases) with different systolic blood pressure (SBP) control targets within 48 h. The patients in group A were given early active antihypertensive treatment with SBP control target of 130-140 mm Hg; those in group B received standard antihypertensive treatment with SBP control target of 170-180 mm Hg. The changes in the volume of hematomas and the patients' prognosis were compared between the two groups.</p><p><b>RESULTS</b>After 48 h of treatment, SBP, hematoma volume and the National Institutes of Health Stroke Scale (NIHSS) score were significantly lower and Glasgou Coma Scale (GCS) score was significantly higher in group A than in group B (P<0.01 or 0.05). After 30 days of treatment, the patients in group A showed significantly better indicators of treatment efficacy than those in group B (Z=2.331, P=0.020). The mortality rate was lower in group A than in group B, but the difference was not statistically significant (Χ=2.772, P=0.096).</p><p><b>CONCLUSION</b>Early active antihypertensive treatment is safe and feasible in patients with HCH and can reduce the enlargement of the hematomas, alleviate deterioration of neurological function, and improve the prognosis of the patients.</p>

GbWRKY1, a novel cotton (Gossypium barbadense) WRKY gene isolated from a bacteriophage full-length cDNA library, is induced by infection with Verticillium dahliae.

WRKY transcription factor proteins play important roles in diverse stress responses. In this study, we first cloned a novel WRKY from our constructed bacteriophage full-length cDNA library for cotton (Gossypium barbadense). The plants were stressed by exposure to a defoliating strain of Verticillium dahliae. The capacity of primary cDNA library was 1.28 × 106 PFU and the titer of the amplified cDNA library was >1010 PFU mL–1. The recombination rate of the library was 94% and average insert size was about 1.1 kb. This novel gene, named GbWRKY1 was 1971 bp long and encodes a protein of 489 amino acids. It contains two characteristic WRKY domains and two zinc finger motifs. The sub-cellular assay indicated that GbWRKY1–GFP fusion protein was localized in the nucleus. Furthermore, Northern blot analysis showed that expression pattern of GbWRKY1 was similar among tissue types (roots, stems and leaves), but differed between pathogen-infiltrated and Czapek medium-infiltrated (untreated control) plants. Quantitative real-time PCR showed that GbWRKY1 could also be induced by salicylic acid (SA), methyl jasmonate (MeJA) and 1-aminocyclopropane-1-carboxylic acid (ACC). These findings clearly suggest that as a pathogen-inducible transcription factor GbWRKY1 plays an important role in plant defense responses.

Effect of Notch signaling on the activation of hepatic stellate cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate whether Notch signaling is activated in hepatic stellate cells (HSCs), and to determine whether manipulation of the Notch signaling pathway can effect the activation of HSCs.</p><p><b>METHODS</b>The expression of Notch signaling components in unactivated or TGF-b1-activated HSC-T6 cells was detected by Taqman Probe-based gene expression analysis. Differential expression of Notch3 and Jagged1 was detected by immunofluorescence analysis. Notch3-mediated expression of the myofibroblastic markers, a-SMA and collagen I, was detected in HSC-T6 cells transfected with pcDNA3.1-N3ICD or Notch3 siRNA by Western blotting.</p><p><b>RESULTS</b>Notch signaling components were expressed in both unactivated and activated HSC-T6 cells, but the TGF-b1-treated cells showed significantly higher expression levels of Jagged1 (3.9-fold, F = 2543.482), Notch3 (4.2-fold, F = 287.982), and HES1 (3.2-fold, F = 1719.851). Transfection-mediated over-expression of Notch3 led to significantly increased expression of a-SMA (6.8-fold, t = 13.157) and collagen I (5.5-fold, t = 9.810) (both P less than 0.01). Transient knock-down of Notch3 expression by siRNA decreased expression of the myofibroblastic markers (a-SMA by approximately 90%, t = 19.863 and collagen I by 84%, t = 10.376; both, P less than 0.01). Moreover, knock-down of Notch3 antagonized the TGF-b1-induced expression of a-SMA and collagen I.</p><p><b>CONCLUSION</b>Notch signaling may participate in liver fibrogenesis by regulating HSC activation. Selective interruption of Notch3 may represent a new anti-fibrotic strategy to treat liver fibrosis.</p>

Enhancement of antiviral immunity in HBV mouse model by blocking PD-1/PD-L1 signaling pathway / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish a mouse model for human chronic HBV infection, and to investigate the role of PD-1/PD-L1 signaling pathway in antiviral immunity.</p><p><b>METHODS</b>A mouse model was established by hydrodynamic injection of the plasmid pAAV/HBV1.2-GFP into the tail vein of C57BL/6 mice, HBV markers were assayed at different time points after injection. After intraperitoneal injection of anti-PD-L1 monoclonal antibody, the serum ALT, and HBV DNA in the serum, liver and kidney were assayed.</p><p><b>RESULTS</b>The chronic HBV infection mouse model were established successfully, serum HBsAg and high load of HBV DNA were detectable 90 days after plasmid injection. After blocking of the PD-1/PD-L1 pathway, the serum ALT level of mice were significantly increased (P < 0.01), and the HBV DNA load in serum (P < 0.01), liver (P < 0.05) and kidney (P < 0.05) were decreased significantly.</p><p><b>CONCLUSION</b>Blocking the PD-1/PD-L1 signaling pathway can enhance antiviral response in mice with chronic HBV infection.</p>

In vitro anti-inflammatory effects of different solution fractions of ethanol extract from Melilotus suaveolens Ledeb / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Melilotus suaveolens Ledeb (M. suaveolens Ledeb) has long been used as a folk medicine in inflammation-related therapy. This study was undertaken to determine the anti-inflammatory effect of the plant.</p><p><b>METHODS</b>Petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, aqueous fraction were obtained from ethanol extract of M. suaveolens Ledeb and evaluated by high performance liquid chromatography (HPLC). While dexamethasone (DM) was used as a positive control, the effects of different solution fractions of ethanol extract on tumor necrosis factor alpha (TNF-alpha) mRNA, cyclooxygenase 2 (COX-2) mRNA, COX-2 and nuclear factor kappaB (NF-kappaB) of LPS-stimulated RAW 264.7 cells were studied by real-time PCR, Western blot analysis and immunocytochemical assay, respectively.</p><p><b>RESULTS</b>Coumarin was one of the main ingredients in different solution fractions of ethanol extract except the aqueous fraction with no inflammatory effect. The petroleum ether fraction, ethyl acetate fraction and n-butanol fraction of ethanol extract could inhibit the production of TNF-alpha mRNA, COX-2 mRNA and NF-kappaB to some extent.</p><p><b>CONCLUSIONS</b>Different solution fractions of ethanol extract from M. suaveolens Ledeb had similar anti-inflammatory effect as did dexamethasone except the aqueous fraction. Coumarin was likely to be essential to the anti-inflammatory effect, and other ingredients might attribute to their different anti-inflammatory effects from the HPLC fingerprint.</p>

Relationship between expression of bcl-2 gene and neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage / 实用儿科临床杂志

Objective To observe the expression of bcl-2 gene in cell apoptosis of neonatal rats followed by hypoxic-ischemic brain damage(HIBD) and investigate the mechanism of neuronal apoptosis after HIBD.Methods Fifty-four neonatal SD rats were used in 1 sham-operated group and 8 trial groups. The models of HIBD were established in neonatal rats by inhaling the mixed gases of 92 % N 2 and 8 % O 2, the animals were sacrificed by dislocation their heads at different time points(0.5,1,3,6,12,24,48,72 h), the hippocampus were dissected for morphological analysis. The neuronal apoptosis and the expression of bcl-2 gene in hippocampus were detected by the methods of immunohistochemistry. Results The apoptotic cells appeared at the time point of 3 h, and reached the peak at 48 h, then decreased. The positive cell of bcl-2 protein increased from the time point of 30 min and reached the peak at 6 h and then decreased gradually following HIBD. Conclusion The expression of bcl-2 gene plays a role in the process of neuronal apoptosis following HIBD.