Background Age-related cataract is one of the common causes of blindness.Although the pathophysiology of age-related cataract is far from clearly understood,it is well accepted that DNA damage plays an important role in the disease pathogenesis.Objective The purpose of this study was to quantitatively evaluate the DNA damage in peripheral lymphocytes of age-related cataract.Methods A cross-sectional study was carried out.This study complied Declaration of Helsinki and approved by Ethic Committee of Affiliated Hospital of Nantong University.Written informed consent was obtained from each subject.Two hundred and eleven patients with agerelated cataract and 147 normal subjects were enrolled from a “ Jiangsu Eye Study:Funing 2011 Eye Disease Epidemic Survey”.All the subjects aged from 50 through 80 years with matched age and gender between the two groups.The percentage of tail DNA and Olive tail moment (OTM) were detected by comet assay to assess the extent of DNA damage in peripheral lymphocytes.Statistical analyses were performed with SPSS 17.0 software,and the differences of the percentage of tail DNA and OTM were compared between the age-related cataract group and normal control group by independent sample t test as well as among the 50-59 years group,60-69 years group and ≥70 years group by one-way analysis of variance.Results Comet assay showed a round lymph cell with the clear border in the normal group;while in the age-related cataract group,the cell was bigger with a comet-like tail.The percentage of tail DNA and OTM in peripheral lymphocytes were (21.75 ± 3.51) ％ and 6.54 ± 1.65 in the age-related cataract group,and those in the normal control group were (9.31 ±3.60)％ and 2.18 ± 1.10,respectively,with significant differences between them (t =32.67,P =0.00 ; t =28.02,P =O.00).In the 50-59 years subgroup of the age-related cataract group,the percentage of tail DNA and OTM in peripheral lymphocytes were (20.04±2.86) ％ and 5.92± 1.14,and in the 60-69 years subgroup of the age-related cataract group,the percentage of tail DNA and OTM in peripheral lymphocytes were (20.77 ±2.93) ％ and 6.13 ± 1.14,which were significantly reduced in comparison with (22.79 ± 3.67)％ and 6.95±1.91 of the ≥70years subgroup(TailDNA％:q=2.75,P=0.00; q=2.02,P=0.00;OTM:q=1.03,P =0.02 ; q =0.82,P =0.00).Conclusions The pathogenesis and development of age-related cataract probably is associated with DNA damage.

OBJECTIVETo study the subcellular localization of severe fever with thrombocytopenia syndrome virus (SFTSV) in macrophages and understand the replication and assembly mechanism of SFTSV in host cells.

METHODSUsing two types of human macrophage cell lines THP-1 and U937, the study analyzed the intracellular colocalization of SFTSV with Golgi apparatus and endoplasmic reticulum by immunefluorescence staining and confocal microscopy.

RESULTSSFTSV infected macrophage cell lines THP-1 and U937. Immunofluorescence staining showed that the SFTSV nuclear protein colocalized with Golgi apparatus and closely surrounded by endoplasmic reticulum in the perinuclear region.

CONCLUSIONThe results suggested that Golgi complex and endoplasmic reticulum are probably the sites for formation and maturation of SFTSV viral particles.

Bunyaviridae ; isolation & purification ; Cell Line, Tumor ; Endoplasmic Reticulum ; virology ; Fever ; virology ; Golgi Apparatus ; virology ; Humans ; Macrophages ; virology ; Thrombocytopenia ; virology

Adolescent ; Adult ; Child ; Female ; Fracture Fixation, Intramedullary ; methods ; Humans ; Male ; Radius Fractures ; surgery

BACKGROUNDThe role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention.

METHODSOne hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n = 52) and control group (n = 62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of ≥ 25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty.

RESULTSPatients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P = 0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64 ± 16.38) ml · min⁻¹·1.73 m⁻² to (67.30 ± 11.99) ml · min⁻¹·1.73 m⁻² in control group (P = 0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (ΔeGFR) between two groups (benazepril group (0.67 ± 12.67) ml · min⁻¹·1.73 m⁻² vs. control group (-3.33 ± 12.39) ml · min⁻¹·1.73 m⁻², P = 0.092). In diabetic subgroup analysis, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant.

CONCLUSIONSBenazepril has a protective effect on mild to moderate impairment of renal function during coronary angioplasty. It is safe to use benazepril for treatment of patients with mild to moderate impairment of renal function before coronary intervention.

Acute Kidney Injury ; chemically induced ; prevention & control ; Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Angiotensin-Converting Enzyme Inhibitors ; Benzazepines ; therapeutic use ; Contrast Media ; adverse effects ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Renal Insufficiency ; complications

OBJECTIVETo investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming (KM) and C57BL6/J (C57) mice.

METHODSElectrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration (APD) in conventional and programmed electrical stimulation (PES). Transient outward potassium current (Ito) was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes.

RESULTSQT interval was prolonged in KM mice relative to C57 mice (62.51±4.47 ms vs. 52.59±4.85 ms, P<0.05) The APD at 50% repolarization of the left ventricular epicardium (18.60±0.91 ms vs. 12.90±0.35 ms), and APDs at 50% (17.31±6.05 ms vs. 12.00±3.24 ms) and 70% repolarization (36.13±5.32 ms vs. 21.95±8.06 ms) of the right ventricular epicardium in KM mice were more sensitive to PES-induced ventricular tachycardia (25%, 3 of 12 hearts), and especially to Burst-induced ventricular tachycardia (50%, 6 of 12 hearts)compared with C57 mice, which were 20% (2 of 10 hearts) and 30% (3 of 10 hearts) respectively. Ito densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively (all P<0.01).

CONCLUSIONOur data showed that KM mice with the prolonged QT interval and APD are vulnerabilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes obtained from KM mice than that from C57 mice.

Animals ; Cells, Cultured ; Electrophysiologic Techniques, Cardiac ; Electrophysiological Phenomena ; physiology ; Heart ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Myocytes, Cardiac ; cytology ; physiology ; Perfusion ; Species Specificity

OBJECTIVETo transfect a short hairpin RNA (shRNA) against survivin gene into human T lymphoblastic leukemia cell line Jurkat, and to explore the effects on apoptosis and proliferation of transfected cells.

METHODSThe survivin-shRNA expression vector were constructed and transfected into Jurkat cells. Expression of survivin mRNA and protein were assessed by RT-PCR and Western blot analysis respectively. Apoptosis index of transfected Jurkat cells was quantified by flow cytometry. The potential of cell proliferation was described by cell growth curves.

RESULTSIn survivin-shRNA transfected Jurkat cells, survivin mRNA levels were significantly reduced by 66.67% ( transient transfection) and 60.69% ( stable transfection) respectively, compared with that in control-shRNA treated group and PBS treated group (P < 0.05); and the levels of survivin protein were significantly reduced by 63.41% (transient transfection) and 60.18% (stable transfection), compared with that in the two control groups (P < 0.05). Apoptosis index was significantly increased during both transient and stable transfection, respectively [(22. 41 +/- 2.83)% and (20.73 +/- 2.56)% (P < 0.05)]. Survivin-shRNA also inhibited the proliferation of Jurkat cells.

CONCLUSIONSVector-based survivin-shRNA can effectively reduce the expression of survivin gene, induce apoptosis

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Gene Expression ; Gene Silencing ; Humans ; Inhibitor of Apoptosis Proteins ; Jurkat Cells ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA Interference ; RNA, Messenger ; biosynthesis ; RNA, Small Interfering ; pharmacology

OBJECTIVETo investigate the impact of depression on clinical outcome of patients undergoing revascularization.

METHODSSelf-rating depression scale (SDS) assessment was made before and after coronary artery bypass grafting (CABG, n = 345) and percutaneous coronary intervention (PCI, n = 308) procedure. Patients were divided into depression and non-depression group. All patients were followed up for 12 months after procedure for the occurrence of rehospitalization and major adverse cardiovascular events (MACE) including all-cause mortality, nonfatal myocardial infarction or target lesion revascularization.

RESULTSDepression was present in 40.9% (n = 141) of patients after CABG, which was significantly higher than before procedure (24.3%, P < 0.01). The MACE rate was significantly higher in patients with post-procedure depression [8.5% (12/141)] than in patients without depression [2.9% (6/204), P < 0.05] and the incidences of target lesion revascularization and rehospitalization were also significantly higher in depression patients than in non-depression patients during the 12 months follow-up (all P < 0.05). Depression was present in 36.4% (n = 112) of patients after PCI, which was significantly higher than that before procedure (28.6%, P < 0.05). The MACE rate [8.0% (9/112) vs. 2.0% (4/196)] and rehospitalization rate [12.5% (14/112) vs. 4.6% (9/196)] were significantly higher in depression patients than in patients without depression during the 12 months follow-up (P < 0.05). There was no significant difference on SDS score between the PCI and CABG before the procedure. However, after the procedure, the SDS score for patients undergoing CABG was significantly higher than in patients undergoing PCI (48.9 ± 9.8 vs. 45.7 ± 10.5 P = 0.01). The level of serum IL-6 was significantly higher in depression patients than in patients without depression (P < 0.05).

CONCLUSIONPrevalence of depression is high in patients treated with revascularization procedures and is linked with poor post-procedure prognosis.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Bypass ; Coronary Disease ; diagnosis ; psychology ; therapy ; Coronary Stenosis ; Depression ; etiology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Treatment Outcome

The severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative pathogen of an emerging infectious disease severe fever with thrombocytopenia syndrome and a new member in the genus Phlebovirus of family Bunyaviridae. Immune responses and pathological lesions in SFTSV-infected Balb/C mice and hamsters were evaluated by inoculation of SFTSV at 105 TCID50 or 103 TCID50 per animal through four different routes of infection, including intravenous, intramuscular, intraperitoneal, and intracerebral injections. The vehicle control groups were also included. At different time points after the inoculation blood and plasma samples were collected. Blood cell counts, blood viral RNA copies, and plasma antibodies were detected by automatic blood cell counters, real-time PCR, and luminex assays, respectively. At two weeks post inoculation, the animals were sacrificed. Tissues including heart, liver, spleen, lung, kidney, intestine, muscle, and brain, were collected for pathological analyses. Results showed that the SFTSV could infect Balb/C mice and hamsters with SFTSV-specific immunoglobulin (Ig) M and IgG antibodies detected in plasma samples on day 7 post inoculation. The SFTSV-specific IgM levels peaked on day 7 post inoculation and then decreased, whereas the SFTSV-specific IgG levels started to increase on day 7 and then peaked on day 14 post inoculation. Pathological analyses indicated significant pathological lesions in liver and kidney tissues. In conclusion, SFTSV could can infect different strains of rodent animals and cause similar immunological and pathological responses.
Animals ; Antibody Specificity ; Bunyaviridae Infections ; blood ; pathology ; Cricetinae ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Leukocyte Count ; Mice ; Mice, Inbred BALB C ; Organ Specificity ; Phlebovirus ; immunology ; physiology

In order to develop potent antidiabetic agents that have inhibitory effect to a-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-41 were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol x L(-1). The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
Acetamides ; Glycoside Hydrolase Inhibitors ; chemical synthesis ; pharmacology ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Molecular Docking Simulation ; Structure-Activity Relationship ; alpha-Glucosidases ; metabolism