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.

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

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

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

Objective To explore the relationship between the incidence of hypoglycemia in infants of diabetic mothers and brain injury.Methods The incidence of 86 infants of diabetic mothers combined with hypoglycemia as well as the relationship time of persistent hypoglycemia of infants were studied.And the association of the incidence and degree of brain injury with the time of persistent hypoglycemia,complication of other diseases and symptomatic hypoglycemia was also investigated.Results Seventy-five cases of temporary hypoglycemia(87.2%),and 11 cases of frequent hypolycemia(12.8%)were observed in the study.In the group of unsatisfactory maternal blood glucose control cases,the incidence of frequent hypoglycemia was 19.4%;in the group of satisfactory maternal blood glucose control cases,the incidence of frequent hypoglycemia was 8%.The overall incidence of the brain injury and the incidence of severe brain injury in the group of frequent hypoglycemic cases were higher than those in the group of temporary hypoglycemic cases.The incidence of brain injury in cases complicated with other diseases(77.4%) and in those with clinical symptoms(81.2%) were significantly higher than those in without other diseases(48.5%) and clinical symptoms(57.4%)(Pa

OBJECTIVETo investigate the synergistic effects of carnosic acid (CA) with arsenic trioxide (As₂O₃) on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects.

METHODSHL-60 cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten (PTEN), Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR) analysis.

RESULTSCA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As₂O₃.

CONCLUSIONCA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Base Sequence ; Blotting, Western ; Cell Cycle ; drug effects ; DNA Primers ; Diterpenes, Abietane ; pharmacology ; Drug Synergism ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Oxides ; pharmacology ; PTEN Phosphohydrolase ; metabolism ; Plant Extracts ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects

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

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