Increased detection of coronary atherosclerosis on 320-slice computed tomographic angiography with burden of cardiovascular risk factors and complications in patients with type 2 diabetes.

AIMS: The cardiovascular risk factors and diabetic complications are related to coronary atherosclerosis. However, the evaluation of the prevalence of coronary atherosclerosis based on their accumulation remains to be determined. METHODS: 247 consecutive Chinese subjects with type 2 diabetes but without history of coronary heart disease (CHD) underwent 320-slice computed tomographic coronary angiography, including no coronary atherosclerosis, non-obstructive atherosclerosis (<50% stenosis) and obstructive atherosclerosis (≥50% stenosis). Conventional cardiovascular risk factors, albuminuria, renal dysfunction and diabetic retinopathy (DR) were determined. Framingham Risk Score (FRS) was used to assess the 10-year CHD risk. RESULTS: Increase in burden of cardiovascular risk factors and diabetic complications were significantly associated with the likelihood of being a higher coronary atherosclerosis category. In the analysis for trend through the categories of burden score or FRS stratification, the percentage of obstructive atherosclerosis was increased and the percentage of no atherosclerosis decreased as the burden score and FRS increased (all p<0.005), respectively. The areas under the receiver operator curve for the burden score versus FRS were greater at predicting coronary atherosclerosis and obstructive atherosclerosis (p=0.004 and p=0.002), respectively. CONCLUSIONS: The prevalence of coronary atherosclerosis was increased with the accumulation of cardiovascular risk factors and diabetic complications. The burden of these clinical and biochemical risk factors has increased ability for prediction of the presence and severity of coronary atherosclerosis over FRS in type 2 diabetic patients.

Diallyl trisufide protects against oxygen glucose deprivation -induced apoptosis by scavenging free radicals via the PI3K/Akt -mediated Nrf2/HO-1 signaling pathway in B35 neural cells.

Oxidative stress contributes to development of ischemic brain damage. Many antioxidants have been proven effective in ameliorating cerebral ischemia injury by inhibiting oxidative stress. DATS, an organosulfuric component of garlic oil, exhibits antioxidative effects. In present study, we used OGD model to investigate the neuroprotective effects of DATS and the mechanisms related to these effects. B35 neural cells exposed to OGD caused a decrease in cell viability and increases in the percentage of apoptotic cells and the level of intracellular cleaved caspase-3, all of which were markedly attenuated by DATS. Further, DATS treatment significantly increased Nrf2 expression and nuclear translocation, upregulated downstream gene HO-1 and inhibited intracellular ROS and MDA generation, all of which were markedly attenuated in cells transfected with Nrf2-specific siRNA. In addition, inhibition of PI3K/Akt signaling by PI3K-specific siRNA not only decreased the expression level of Nrf2 and HO-1 proteins, but also diminished the antioxidative and neuroprotective effect of DATS. Taken together, these results indicate that DATS protects B35 neural cells against OGD-induced cell injury by inhibiting ROS production via upregulating the PI3K/Akt-mediated Nrf2 pathway, which further activates HO-1. Based on our results, DATS may be a potential candidate for intervention in hypoxic-ischemic brain injuries such as stroke.

A time course study about gene expression of post-thermal injury with DNA microarray.

BACKGROUND: Burn injury is one of the most common and devastating forms of trauma in daily life. However, the exact sequence of events after burn injury remains unknown. OBJECTIVE: This study aims to investigate gene expression alterations after burn injury. METHODS: Microarray data set GSE8056 was downloaded from the Gene Expression Omnibus (GEO) database, including 12 samples, equally distributed in four groups: normal skin tissue as control and damaged tissues 1-3 days after burn (early period); 4-7 days after burn (middle period); and more than 7 days after burn (late period). Packages in R language were utilized to pre-process the data and filter out the differentially expressed genes (DEGs). Functional annotation of all three groups of DEGs was conducted by using clusters of orthologous groups analysis. The DEGs shared by all three groups were picked out and analyzed with STRING to set up a protein-protein interaction network. CFinder was chosen to implement module analysis, and expression analysis systematic explorer was then adopted to reveal the dysfunctional pathways for each module. RESULTS: A total of 727, 782, and 445 DEGs were identified in the early, middle, and late period after burn, and 234 DEGs were identified as continually differentially expressed throughout all time periods, including genes encoding proinflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-1ß, and genes associated with cell proliferation. Three modules associated with cell proliferation and inflammatory responses were generated from the protein-protein interaction network. CONCLUSION: Our findings are beneficial for understanding the progression of the wound healing response after burn.

Analysis of protein-protein interaction network and functional modules on primary osteoporosis.

BACKGROUND: Primary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis. Previous studies have shown that primary osteoporosis is associated with gene mutations.To explore the functional modules of the PPI (protein-protein interaction) network of differentially expressed genes (DEGs), and the related pathways participating in primary osteoporosis. METHODS: The gene expression profile of primary osteoporosis GSE35956 was downloaded from the GEO (Gene Expression Omnibus) database and included five MSC (mesenchymal stem cell) specimens of normal osseous tissue and five MSC specimens of osteoporosis. The DEGs between the two types of MSC specimens were identified by the samr package in R language. In addition, the functions and pathways of DEGs were enriched. Then the DEGs were mapped to String to acquire PPI pairs and the PPI network was constructed with by these PPI pairs. Topological properties of the network were calculated by Network Analyzer, and modules in the network were screened by Cluster ONE software. Subsequently, the fronting five modules whose P-value was less than 1.0e-05 were identified and function analysis was conducted. RESULTS: A total of 797 genes were filtered as DEGs from these ten specimens of GSE35956 with 660 up-regulated genes and 137 down-regulated genes. Meanwhile, up-regulated DEGs were mainly enriched in functions and pathways related to cell cycle and DNA replication. Furthermore, there were 4,135 PPI pairs and 377 nodes in the PPI network. Four modules were enriched in different pathways, including cell cycle and DNA replication pathway in module 2. CONCLUSIONS: In this paper, we explored the genes and pathways involved in primary osteoporosis based on gene expression profiles, and the present findings have the potential to be used clinically for the future treatment of primary osteoporosis.

Screening for key genes associated with atopic dermatitis with DNA microarrays.

The aim of the present study was to identify key genes associated with atopic dermatitis (AD) using microarray data and bioinformatic analyses. The dataset GSE6012, downloaded from the Gene Expression Omnibus (GEO) database, contains gene expression data from 10 AD skin samples and 10 healthy skin samples. Following data preprocessing, differentially expressed genes (DEGs) were identified using the limma package of the R project. Interaction networks were constructed comprising DEGs that showed a degree of node of >3, >5 and >10, using the Osprey software. Functional enrichment and pathway enrichment analysis of the network comprising all DEGs and of the network comprising DEGs with a high degree of node, were performed with the DAVID and WebGestalt toolkits, respectively. A total of 337 DEGs were identified. The functional enrichment analysis revealed that the list of DEGs was significantly enriched for proteins related to epidermis development (P=2.95E-07), including loricrin (LOR), keratin 17 (KRT17), small proline-rich repeat proteins (SPRRs) and involucrin (IVL). The chemokine signaling pathway was the most significantly enriched pathway (P=0.0490978) in the network of all DEGs and in the network consisting of high degree­node DEGs (>10), which comprised the genes coding for chemokine receptor 7 (CCR7), chemokine ligand (CCL19), signal transducer and activator of transcription 1 (STAT1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In conclusion, the list of AD-associated proteins identified in this study, including LOR, KRT17, SPRRs, IVL, CCR7, CCL19, PIK3R1 and STAT1 may prove useful for the development of methods to treat AD. From these proteins, PIK3R1 and KRT17 are novel and promising targets for AD therapy.

Effects of neurolytic celiac plexus block on liver regeneration in rats with partial hepatectomy.

Liver regeneration is the basic physiological process after partial hepatectomy (PH), and is important for the functional rehabilitation of the liver after acute hepatic injury. This study was designed to explore the effects of neurolytic celiac plexus block (NCPB) on liver regeneration after PH. We established a model of PH in rats, assessing hepatic blood flow, liver function, and serum CRP, TNF-α, IL-1ß and IL-6 concentrations of the residuary liver after PH. Additionally, histopathological studies, immunohistochemistry, and western blotting were also performed. Our results indicated that NCPB treatment after PH improved liver regeneration and survival rates, increased hepatic blood flow, reduced hepatocyte damage, decreased the secretion and release of inflammatory cytokines, increased the expression of B cell lymphoma/leukemia-2 (Bcl-2), and decreased the expression of Bcl-2 associated X protein (Bax). Additionally, Western blotting revealed that the expression of NF-κB p65 and c-Jun were decreased in liver after NCPB. In conclusion, the results of our present study indicate that NCPB treatment has a favorable effect on liver regeneration after PH. We suggest that NCPB can be utilized as an effective therapeutic method to help the functional rehabilitation of the liver after acute hepatic injury or liver cancer surgery.

[Changes of rabbit IL-1 and TNF-alpha, etc cytokines in response to acute normovolemic hemodilution with HAES-balanced solution as diluting agent].

AIM: To observe effect of acute normovolemic hemodilution(ANH) with HAES-balanced solution as diluting agent on levels of cytokines including IL-1, IL-2, IL-6 and TNF-alpha in rabbit serum so as to provide theoretical basis for clinical application. METHODS: A total of 20 healthy adult rabbits were enrolled in the study and randomly divided into two groups (10 rabbits per group), i.e., control group (Group C) and HAES group (Group H). Under anesthesia of the rabbits, we performed incision of trachea, high-frequency jet ventilation and liberation of femoral artery and femoral veins. Group C was free from hemodilution. Group H was injected with dilution (2-fold of blood letting volume) via femoral veins during blood letting of the femoral artery. 6% HAES-steril plus compound solution of sodium lactate, with crystal/gel ratio of 2:1, blood letting volume = TBV x (Ho-Hf)/Hav. All blood was transfused back 60-120 min after blood letting. Venous blood was collected before blood letting (T0) and 30 min (T1), 60 min (T2), 120 min (T3) and 24 h(T4) after blood letting to detect Hb and Hct and measure level of IL-1, IL-2, IL-6 and TNF-alpha in serum. RESULTS: In Group H, levels of IL-1, IL-2, IL-6 and TNF-alpha in serum were increased from T1 after ANH, reached peak at T3 but showed decrease at T4, with significant difference compared with Group C at T1, T2, T3 and T4 (P < 0.01) and significant difference compared with those before ANH (P <0.01). In Group C, there was no significant difference upon IL-1, IL-2, IL-6 and TNF-alpha in serum at different time points. CONCLUSION: ANH with HAES-balanced solution as diluting agent can up-regulate the levels of cytokines IL-1, IL-2, IL-6 and TNF-alpha in rabbit serum. In the meantime, ANH may arouse eustress with low intensity and short action time, which exerts effect of enhancing immune function of the organisms.