Comparisons of Serum Interleukin-8 Levels in Major Depressive Patients With Drug-Free Versus SSRIs Versus Healthy Controls.

Objective: The interleukin-8 (IL-8) has been reported to play an important role in depression, which might be modulated by the selective serotonin reuptake inhibitors (SSRIs). Thus, the aim of this study was to investigate serum IL-8 levels, depressive symptom, and their associations in drug-free MDD patients, MDD patients with SSRIs, and healthy controls (HCs). Methods: Fifty-seven drug-free MDD patients (male/female = 35/22, mean age: 39.24 years), 30 MDD patients with SSRIs (male/female = 11/19, mean age: 39.73 years), and 101 HCs (male/female = 52/49, mean age: 37.38 years) were recruited in this cross-sectional study. Serum IL-8 levels and depressive symptom were assessed using the Flow Cytometer and Hamilton Depression Scale (HAMD). The analysis of variance was used for the comparison between groups. The relationship between serum log10 IL-8 levels and HAMD score was analyzed by Pearson correlation. Results: Serum log10IL-8 levels were lower in all patients than HCs after controlling for covariates (F = 4.86, p = 0.03). There was significant difference in serum Log10IL-8 levels among three groups after controlling for covariates (F = 14.63, p < 0.001). Serum Log10IL-8 levels in drug-free patients were lower compared to HCs (F = 19.38, p < 0.001) or patients with SSRIs (F = 21.89, p < 0.001) after controlling for covariates. However, there was not difference in serum log10IL-8 levels between patients with SSRIs and HCs after controlling for covariates. Moreover, serum Log10IL-8 levels were negatively correlated with HAMD score in all patients (r = -0.37, p = 0.02). Also, serum Log10IL-8 levels were negatively correlated with HAMD score in drug-free patients (r = -0.74, p = 0.01), but not in patients with SSRIs. Conclusion: Our data supported that the decline in serum IL-8 levels was association with depression. Moreover, the SSRIs might modulate increased serum IL-8 levels of depression.

Critical role of PAFR/YAP1 positive feedback loop in cardiac fibrosis.

Aberrant activation of cardiac fibroblasts is the main cause and character of cardiac fibrosis, and inhibition of cardiac fibrosis becomes a promising treatment for cardiac diseases. Platelet-activating factor (PAF) and Hippo pathway is recently recognized as key signaling mechanisms in cardiovascular diseases. In this study we explored the potential roles of PAF and Hippo signaling pathway in cardiac fibrosis. Myocardial infarction (MI) was induced in mice by left anterior descending artery ligation. After 28 days, the mice were sacrificed, and the hearts were collected for analyses. We showed that PAF receptor (PAFR) and yes-associated protein 1 (YAP1, a key effector in the Hippo pathway) were significantly increased in the heart of MI mice. Increased expression of PAFR and YAP1 was also observed in angiotensin II (Ang II)-treated mouse cardiac fibroblasts. In mouse cardiac fibroblasts, forced expression of YAP1 increased cell viability, resulted in collagen deposition and promoted fibroblast-myofibroblast transition. We showed that PAF induced fibrogenesis through activation of YAP1 and promoted its nuclear translocation via interacting with PAFR, while YAP1 promoted the expression of PAFR by binding to and activating transcription factor TEAD1. More importantly, silencing PAFR or YAP1 by shRNA, or using transgenic mice to induce the conditional deletion of YAP1 in cardiac fibroblasts, impeded cardiac fibrosis and improved cardiac function in MI mice. Taken together, this study elucidates the role and mechanisms of PAFR/YAP1 positive feedback loop in cardiac fibrosis, suggesting a potential role of this pathway as novel therapeutic targets in cardiac fibrosis.

Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy - A Safe and Effective Low-Dose Protocol.

AIMS: Regional citrate anticoagulation (RCA) is the preferred mode of anticoagulation for continuous renal replacement therapy (CRRT). Conventional RCA-CRRT citrate dose ranges from 3 to 5 mmol/L of blood. This study explored the effectiveness of an RCA protocol with lower citrate dose and its impact on citrate-related complications. METHODS: This prospective observational study compared two RCA-CRRT protocols in the intensive care unit. RCA Protocol 1 used an initial citrate dose of 3.0 mmol/L while Protocol 2 started with 2.5 mmol/L. The citrate dose was titrated by sliding scale to target circuit-iCa 0.26-0.40 mmol/L. Calcium was re-infused post-dialyzer and titrated by protocol to target systemic-iCa 1.01-1.20 mmol/L. RESULTS: Two hundred RCA-CRRT sessions were performed (81 Protocol 1; 119 Protocol 2). The median age was 65.4 years and median APACHE-II score was 23. Citrate dose for Protocol 1 was significantly higher than Protocol 2 in the first 12 h. The circuit clotting rate was similar in both arms (Protocol 1: 9.9%; Protocol 2: 9.2%; P = 0.881). With Protocol 2, circuit-iCa levels were 2.42 times more likely to be on target (P = 0.003) while the odds of hypocalcaemia was 4.67 times higher with Protocol 1 (P < 0.001). There was a wider anion gap was noted with Protocol 1, which suggests a propensity for citrate accumulation with higher citrate exposure. CONCLUSION: The RCA protocol with a lower initial citrate dose of 2.5 mmol/L blood had less citrate-related complications with no loss of efficacy. A more precise RCA prescription at the start of treatment avoids unnecessary citrate exposure and improves safety.

[Spectrum-effect relationship between UPLC fingerprint of Smilax china and anti-pelvic inflammation in rats].

To study the correlation between ultra high performance liquid chromatography( UPLC) fingerprint of Smilax china and its anti-pelvic inflammatory effect,and to explore the pharmacodynamic material basis of S. china against pelvic inflammatory disease.UPLC fingerprints of 10 batches of S. china from different habitats were established,and the values of SOD,MDA,TNF-α,and IL-6 in rats with pelvic inflammation were measured. The weight of each single pharmacodynamics index to the total efficacy was determined by analytic hierarchy process,and the contribution of each peak in fingerprints to the each single pharmacodynamics index and total efficacy was analyzed by the grey relational analysis. Then the structures of chemical constituents at the identified peaks were confirmed by comparing with the reference substance. The 27 common characteristic peaks of UPLC fingerprints were all related to the anti-pelvic inflammation effect of S. china,of which 13 peaks were identified as peak 2( 3,5-dihydroxy-2-methylbenzoic acid-3-O-glucoside),peak 3( chlorogenic acid),peak 5( 2,7,4-trihydroxydihydroflavone-5-O-glucoside),peak 6( 7,4-dihydroxydihydroflavonol-5-O-glucoside),peak 7( taxifolin-7-O-glucoside),peak 9( taxifolin),peak 10( polydatin),peak 11( oxyresveratrol),peak 12( astilbin),peak15( resveratrol),peak 16( quercitrin),peak 18( engeletin) and peak 24( kaempferol). The correlation degree of 21 peaks and the total efficacy was greater than 0. 8,and the top 10 ranked by correlation degree were as follows: peak 1,3,7,19,18,17,4,11,16,and 21. The results showed that the anti-pelvic inflammation effect of S. china was achieved by the combined action of pharmacodynamic substances. In order to control the quality of S. china and its prepared slices more effectively,the index components of content detection should be selected reasonably.

[5-FU-Injured Bone Marrow Stromal Cells Initiate Stress-induced Premature Senescence of Hematopoietic Cells].

OBJECTIVE: To investigate the damage effect of 5-fluorouracil(5-FU) with tumor inhibition concentration on human bone marrow mesenchymal stem cells (hBMSC) and influence of its effect on the hematopoietic cells. METHODS: The Cell Counting Kit-8 was used for determining the sensitivity of breast cancer cell line MCF-7, colon cancer cell line HCT-116 and HS-5 derived from human bone marrow stronal cell line to the different doses of 5-fluorouracil in vitro. After HS-5 was treated with 5-fluorouracil, crystal violet staining assay was used to count the number of colony forming unit-fibroblast, the distribution of cell cycle was analyzed by flow cytometry (FCM), apoptosis was assessed by Annexin V/PI double-stained method and Hoechest staining; DCFH-DA staining was used to analyse the level of reactive oxygen species (ROS), ELISA and immuofluorescence were used to detect cytokines KL, GM-CSF, RANTS and SDF. The hUCB-MNC was counted by trypan blue staining after co-culture with HS-5, FCM was used to detect the cell cycle distribution, ROS level and the ratio of CD34+ cells. The levels of glutathione peroxidase (GSH-Px) and total superoxide dismutase(T-SOD) were measured by enzymatic assay. The senescence associated-ß-galactosidase (SA-ß-Gal) staining was used to detect the senescent hUCB-MNC. RESULTS: 5-Fluorouracil of 12.5 µg/ml-100 µg/ml inhibited the proliferation of MCF-7, HCT-116 and HS-5 cells in dose-dependent and time-dependent manner, among them HS-5 was more sensitive to 5- fluorouracil. After treatment with 5-fluorouracil, the HS-5 cell cycle was blocked. The apoptosis rate and the intracellular ROS level of HS-5 significantly increased. Also HS-5-secreted hematopoietic growth factors decreased and inflammatory chemokines increased. After co-cultured with 5-fluorouracil-treated HS-5, the number of hUCB-MNC and the ratio of CD34+ cells were decreased. hUCB-MNC cell cycle blocked in G1 phase. The antioxidant capacity also decreased and the intracellular ROS level increased significantly. The senescent hUCB-MNC increased. CONCLUSION: 5-Fluorouracil can result in oxidative damage of bone marrow stromal cells and change of function secreting bioactivators, thus induce oxidative stress in hematopoietic cells to initiate stress-induced premature senescence (SIPS).

[SSR analysis on stress effect of transgenic hybrid poplar 741 on Clostera anachoreta (Fabricius) (Lepidoptera: Notodontidae)]. / é¶æ ‡æ˜†è™«æ¨æ‰‡èˆŸè›¾å¯¹è½¬BtåŸºå› 741杨胁迫效应的SSR分析.

The genetic differentiation of the experimental population of Clostera anachoreta fed on different resistant transgenic 741 poplar leaves was analyzed by SSR molecular marker technique to investigate stress effect of transgenic poplar Bt gene as food on target insect. The experimental population of C. anachoreta fed on transgenic 741 poplar high resistant strains 'Pb29', medium resis-tant strains 'Pb17' and non-transgenic poplar (CK), and the screened ten pairs of SSR primers were used. The results showed that 76 alleles were observed in ten pairs of primers. The average allele was 7.6, the average effective number of alleles was 2.2, the average observed heterozygosity was 0.5167, the average expected heterozygosity was 0.5167, and the average percentage of polymorphic loci was 96.7%. The genetic diversity level of C. anachoreta experimental population fed on transgenic poplar 741 was significantly higher than that fed on non-transgenic populations, and C. anachoreta fed on high resistance had the lowest genetic similarity with CK samples, which showed an increasing trend of the genetic diversity of the experimental population fed on transgenic Bt poplar. It was thus clear that transgenic hybrid poplar 741 had stress effects on genetic differentiation of C. anachoreta experimental population by SSR.