R-I subtype single right coronary artery with congenital absence of left coronary system: A case report.

BACKGROUND: Isolated single coronary artery is a rare congenital anomaly. R-I subtype single coronary artery is even rarer. In this subtype, a very large right coronary artery extends in the coronary sulcus to the anterior base of the heart where it produces the left anterior descending coronary artery. Currently, only a few case reports are available in the literature for this anomaly. CASE SUMMARY: Here, we report the case of a 62-year-old woman who presented to the cardiology clinic with decreased exercise tolerance and poor blood pressure control. The patient underwent coronary angiography (CAG) and emission computed tomography (ECT). CAG images revealed a single gigantic right coronary artery (R-I type) arising from the right coronary sinus with branches supplying the left coronary territory. The ECT results confirmed myocardial ischemia at the location of the absent left coronary artery. The ECT findings confirmed that ischemia was consistent with the vascular loss location in CAG images. In such anomalies, there is a compensatory widening of the coronary artery lumen. Medical treatment was administered, and the patient was discharged. CONCLUSION: Isolated single coronary arteries are associated with ischemia and potentially fatal acute coronary events. Hence, controlling risk factors is critical.

Histone deacetylase-2 expression and activity in children with nephrotic syndrome with different glucocorticoid response.

BACKGROUND: Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children. METHODS: Forty-eight patients with PNS suffering from their first attack prior to GC treatment were chosen as subjects. They were divided into two groups, those who had steroid-sensitive nephrotic syndrome (SSNS; n = 25) and those with steroid-resistant NS (SRNS; n = 23), according to their response to a 6-week course of oral prednisone. Twenty healthy children from the Physical Examination Center in the hospital served as the control group; Peripheral blood was collected at different time points prior to GC treatment and after regular therapy. RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA) techniques were adopted to analyze HDAC2 mRNA, protein expression, and activity, respectively, in peripheral blood lymphocytes. The level of interleukin-8 (IL-8) in serum was measured by an ELISA. RESULTS: Prior to GC treatment, HDAC2 expression level and activity were lower in the SRNS group than in the SSNS and control group. A statistically significant difference in HDAC2 expression and activity were observed after GC treatment between these groups, with HDAC2 expression and activity lower in the SRNS group than in the SSNS and control groups. In the SSNS group, the expression and activity of HDAC2 were higher following GC treatment than prior to GC treatment. There was a clear difference in HDAC2 expression and activity of SRNS at the different time points. No statistically significant difference was found between the two groups. The pre-treatment and post-treatment serum IL-8 levels in the SRNS group were significantly higher than those in the SSNS group. HDAC2 from children with PNS before GC treatment and after regular therapy for 6 weeks was negatively correlated with serum IL-8 level. CONCLUSION: The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS.

The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3ß Inactivation.

Glycogen synthase kinase-3ß (GSK-3ß) acts as a negative regulator of NF-E2 related factor 2 (Nrf2) by inducing Nrf2 degradation and nuclear export. Our previous study demonstrated that the flavonoid hyperoside elicits cytoprotection against oxidative stress by activating the Keap1-Nrf2-ARE signaling pathway, thus increasing the expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and catalase. However, the role of GSK-3ß in hyperoside-mediated Nrf2 activation is unclear. Here, we demonstrate that in a normal human hepatocyte cell line, (L02), hyperoside is capable of inducing the phosphorylation of GSK-3ß at Ser9 without affecting the protein levels of GSK-3ß and its phosphorylation at Thr390. Lithium chloride (LiCl) and short interfering RNA (siRNA)-mediated inhibition of GSK-3ß significantly enhanced the ability of hyperoside to protect L02 liver cells from H2O2-induced oxidative damage, leading to increased cell survival shown by the maintenance of cell membrane integrity and elevated levels of glutathione (GSH), one of the endogenous antioxidant biomarkers. Further study showed that LiCl and siRNA-mediated inhibition of GSK-3ß increased hyperoside-induced HO-1 expression, and the effect was dependent upon enhanced Nrf2 nuclear translocation and gene expression. These activities were followed by ARE-mediated transcriptional activation in the presence of hyperoside, which was abolished by the transfection of the cells with Nrf2 siRNA. Furthermore, the siRNA-mediated inhibition of Keap1 also enhanced hyperoside-induced Nrf2 nuclear accumulation and HO-1 expression, which was relatively smaller than the effects obtained from GSK-3ß siRNA administration. Moreover, Keap1 siRNA administration alone had no significant effect on the phosphorylation and protein expression of GSK-3ß. Collectively, our data provide evidence that hyperoside attenuates H2O2 -induced L02 cell damage by activating the Nrf2-ARE signaling pathway through both an increase in GSK-3ß inhibitory phosphorylation at Ser9 and an inhibition of Keap1 and that hyperoside-mediated GSK-3ß inhibition exhibits more significant effects.

[Study on main pharmacodynamic effects for Schisandra lignans based upon network pharmacology].

In this study, we focused on the study of pharmacodynamic effects for 6 major bioactive lignans of Schisandra chinensis, namely deoxyschizandrin, schisandrin B, schisandrin C, schisandrin, schizandrol B and schisantherin A. A compound-gene-pathway network, which contained 124 related genes and 88 pathways, was constructed by collecting drug genes through mining relevant literatures and network pharmacology analysis. Based on the network analysis, 32 pathways and 80 related genes were associated with inflammation, which implied that anti-inflammatory might be the major pharmacodynamic effects of these compounds. All lignans except schizandrol B reduced LPS-induced NO production in RAW264.7 cells, which validated the anti-inflammatory hypothesis generated from network analysis. Furthermore, we investigated the effects of deoxyschizandrin, schisandrin C, schisandrin and schisantherin A on the secretion of inflammatory cytokines TNF-α, IL-1ß, IL-6, PGE2 and protein expressions of iNOS, COX-2. As a result, deoxyschizandrin showed the strongest anti-inflammatory activity with inhibitory effect on all 4 inflammatory cytokines secretions and protein expressions of iNOS, COX-2. This study provided evidences for systematic exploration on the pharmacolgical actions and mechanisms of schisandra.

[Network pharmacology study of mechanism on xuesaitong injection against retinal vein occlusion].

Retinal vein occlusion (RVO) is a common clinical disease causing vision loss. Risk factors such as diabetes, atherosclerosis are closely associated with RVO. Xuesaitong injection is used extensively in clinical treatment of RVO, however the mechanism is still unclear. In this study, we investigated the protective effect of Xuesaitong injection on RVO rat model. Using a compound-target network of Xuesaitong on anti-RVO constructed by literature mining, we aim to elucidate the multi-compound, multi-target effect of Xuesaitong injection. Fifteen potential targets of Xuesaitong injection associated with inflammation, angiogenesis, apoptosis, and coagulation were identified in this study. VEGF, IL-1beta and IL-6, three important targets in the compound-target network were further experimentally validated. This study provided experimental evidence for Xuesaitong injection being effective in treating RVO and a network view on its anti-RVO mode of action through a multi-compound and multiple-target mechanism.

Effect of Trichinella spiralis infection on expression and distribution of colonic epithelial E-cadherin in mice and its mechanism / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the effect of Trichinella spiralis (T.spiralis) infection on the expression and distribution of colonic epithelial E-cadherin in mice and its mechanism.</p><p><b>METHODS</b>BALB/c mice and STAT6-/- mice were infected with T.spiralis, and mice without infection were used as control. Seven days later, the horseradish peroxidase (HRP) was infused by rectal enema. Serum HRP was detected in the subsequent 0, 60 and 120 minutes. Then the mice were sacrificed and colon was taken out. The distribution of E-cadherin in colon was detected by immunofluorescence staining, and the expression of E-cadherin was detected by Western blot. The expression of interleukin-4 (IL-4) in mesenteric lymph nodes was detected by ELISA.</p><p><b>RESULTS</b>Serum HRP level in infected BALB/c mice was significantly higher than that in control mice (P<0.05), while it was not significantly different between infected STAT6-/- mice and controls (P>0.05). In infected BALB/c mice, E-cadherin located in cytoplasm of colonic epithelial cells, while in controls, it located in cellular membrane. E-cadherin expression down-regulated significantly in infected BALB/c mice as compared to controls. E-cadherin expression and distribution did not change obviously in infected STAT6-/- and control mice. IL-4 level in mesenteric lymph nodes of infected BALB/c mice [(193.0±12.5) μg/L] was significantly higher as compared to control BALB/c and infected STAT6-/- mice [(21.0±2.3) μg/L and (15.0±3.1) μg/L, all P<0.05].</p><p><b>CONCLUSION</b>T.spiralis infection can increase colonic epithelial permeability of mice, which may be associated with induction of Th2 cytokine secretion.</p>

Impact of fragile histidine triad gene transfection on the proliferation and apoptosis of human colorectal cancer cell / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of fragile histidine triad (FHIT) gene transfection on human colorectal cancer cell line SW480 through up-regulation of caspase-8 expression.</p><p><b>METHODS</b>The eukaryotic expression plasmid containing FHIT, pRc/CMV2-FHIT was prepared and purified, and then identified by restrictive enzyme digestion. pRc/CMV2-FHIT was transfected into SW480 cells, and positive cell clones (SW480-FHIT, study group) were selected and amplified. Empty plasmid-transfected SW480 cells(SW480-pRc/CMV2, negative control) and normal SW480 cells (bland control) were used as control. Methyl thiazolyl tetrazolium (MTT) assay was used to test the changes in the proliferation of SW480 cells. Cell-cycle kinetics and apoptosis were analyzed by flow cytometry (FCM). The changes of pro-caspase-8, caspase-8 mRNA and caspase-8 relative activity were analyzed by Western blot, semi-quantitative RT-PCR and colorimetric assay with pan labeled substrate, respectively.</p><p><b>RESULTS</b>At 96 hours after transfection, cell inhibition rates of the study group and the negative control group were 71.7% and 16.9%. G0/G1 ratio was (63.2±3.5)% and (50.6±2.1)%, optical density of caspase-8 mRNA band 107 and 41, and relative activity of caspase-8 0.43 and 0.25, respectively. All the differences above were statistically significant (P<0.05). When FHIT inhibitor was added, the relative activity of caspase-8 decreased to 0.22, comparable to that in the control group.</p><p><b>CONCLUSIONS</b>FHIT gene transfection can significantly inhibit the proliferation and induce G0/G1 arrest in human colon cancer cell line SW480. The mechanism is related to the up-regulation of caspase-8 expression.</p>

Influence of Mg2+ and Cd2+ on the interaction between sparfloxacin and calf thymus DNA.

Mg(2+) and Cd(2+) have different binding capacity to sparfloxacin, and have different combination modes with calf thymus DNA. Selecting these two different metal ions, the influence of them on the binding constants between SPFX and calf thymus DNA, as well as the related mechanism have been studied by using absorption and fluorescence spectroscopy. The result shows that Cd(2+) has weak binding capacity to SPFX in the SPFX-Cd(2+) binary system, but can decrease the binding between SPFX and DNA obviously in SPFX-DNA-Cd(2+) ternary system. Mg(2+) has strong binding capacity to SPFX. It can increase the binding between SPFX and DNA at concentrations <0.01 mM, and decrease the binding between them at concentrations >0.01 mM. Referring to the different modes of Mg(2+) and Cd(2+) binding to DNA, the mechanism of the influence of metal ions on the binding between SPFX and DNA has been proposed. SPFX can directly bind to DNA by chelating DNA base sites. If a metal ion at certain concentration mainly binds to DNA bases, it can decrease the binding constants between SPFX and DNA through competing with SPFX. While if a metal ion at certain concentration mainly binds to phosphate groups of DNA, it can increase the binding constants by building a bridge between SPFX and DNA. The influence direction of metal ions on the binding between quinolone and DNA relays on their binding ratio of affinity for bases to phosphate groups on DNA. Our result supports Palumbo's conclusion that the binding between SPFX and the phosphate groups is the precondition for the combination between SPFX and DNA, which is stabilized through stacking interactions between the condensed rings of SPFX and DNA bases.

Fragile histidine triad protein expression and correlation with apoptosis in rectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the expression of fragile histidine triad (FHIT) protein and the clinicopathological characteristics of rectal carcinoma. The relationship between FHIT protein expression and Bcl-2, Bax and survivin expression, as well as cell apoptosis in rectal carcinoma were explored.</p><p><b>METHODS</b>Tissue microarray and immunohistochemistry SP were used to detect the expression of FHIT, Bcl-2, Bax and Survivin in 16 cases of normal rectal tissue, 16 cases of rectal adenoma and 80 cases of rectal carcinoma. TUNEL was used to detect apoptosis index (AI) in 80 cases of rectal carcinoma.</p><p><b>RESULTS</b>The positive rates of FHIT expression in normal rectal tissue, rectal adenoma and adenocarcinoma were 93.8%, 75.0% and 46.3% respectively. There were no significant differences between FHIT expression and histological types, gender and age (P>0.05). FHIT expression was significantly correlated with lymph node metastasis, Duke's stage and 5-year survival rate. The expression of FHIT was positively correlated with that of Bcl-2, Bax and survivin in rectal cancer. The mean AI in FHIT-negative tumors was significantly lower than that in FHIT-positive tumors (P<0.01).</p><p><b>CONCLUSIONS</b>The reduction of FHIT protein expression may play an important role in the development of rectal carcinoma, and FHIT protein may be associated with the regulation of cell apoptosis.</p>