Miracle-dz/UniFAR-FTUs huggingface dataset:
Bavachalcone-Induced Manganese Superoxide Dismutase Expression through the AMP-Activated Protein Kinase Pathway in Human Endothelial Cells

Mitochondrial oxidative stress has been suggested as a major etiological factor in cardiovascular diseases. Manganese superoxide dismutase (MnSOD) is an essential antioxidant mitochondrial enzyme. Although polyphenols can induce MnSOD expression, their mechanism of action remains unclear. We examined the effect of bavachalcone, a bioactive compound isolated from Psoralea corylifolia, on MnSOD protein expression and explored whether this effect is mediated through the AMP-activated protein kinase (AMPK) signaling pathway. Our data showed that bavachalcone enhanced the luciferase activity of the MnSOD promoter and increased MnSOD mRNA and protein expressions. Moreover, bavachalcone suppressed the mitochondrial superoxide production in endothelial cells. Conversely, bavachalcone stimulated liver kinase B1 and AMPKα phosphorylation. mRNA interference by using short hairpin RNA (shRNA) of AMPK inhibited bavachalcone-induced MnSOD expression. A-769662, an AMPK activator, also stimulated AMPK activity and increased MnSOD expression. Furthermore, AMPK knockdown by shRNA-AMPK reversed the inhibitory effects of bavachalcone on mitochondrial superoxide production in endothelial cells. These findings indicate that bavachalcone can protect the endothelial function by increasing AMPK activity and MnSOD expression and reducing mitochondrial oxidative stress.
Cognitive reserve and mortality in dementia: the role of cognition, functional ability and depression

Objective. This study examined whether dementia patients with greater cognitive reserve had increased mortality rates, and whether this association was different across strata of cognition, functional ability and depression. Methods. In the community-based Amsterdam Study of the Elderly, 261 non-institutionalized dementia patients, identified using the Geriatric Mental State Schedule (GMS), were followed for an average of 55·5 months after which mortality data were obtained. Cognitive reserve was indicated by years of education and pre-morbid intelligence (measured using the Dutch Adult Reading Test). Cognition, functional ability and depression were indicated by Mini-Mental State scores, ADL and IADL measurements and GMS depressive syndrome, respectively. Results. During the follow-up 146 persons (55·9%) died. Cox regression analyses showed that more highly educated dementia patients had higher mortality rates, only if they had low MMSE scores or if they had a concurrent depression. Pre-morbid intelligence was associated with a higher mortality rate, independent of cognition, but this association was much stronger among patients with depression. The positive association between education or intelligence and mortality was not modified by functional disabilities. Conclusions. The results suggest that dementia patients with greater cognitive reserve have increased mortality rates, only if the disease has progressed to such an extent that clinical symptoms are more severe. In this respect, the reserve hypothesis needs a modification. Depression in dementia patients with greater cognitive reserve may reflect a subgroup of patients with poor prognosis.
Development of a simple broadband microstrip to waveguide transition

A novel microstrip to waveguide transition fabricated on a single substrate is proposed. The transition is based on a proximity fed E-shaped patch antenna element which allows for double resonances. Thus the bandwidth of the transition can approximately be doubled compared to a transition which utilizes a regular patch element without increasing the transversal dimensions. The influence of the critical patch parametersisdiscussed. Numerical results show aninputreflectioncoefficientbelow-15dBbetween15.97GHz and 16.49GHz andaminimal insertion lossof1dB. The bandwidth is approximately 3.2% at the center frequency of operation (16.23 GHz). Measurement results of the fabricated transition are presented and compared with simulation results.
Role of Klebsiella pneumoniae Type 1 and Type 3 Fimbriae in Colonizing Silicone Tubes Implanted into the Bladders of Mice as a Model of Catheter-Associated Urinary Tract Infections

ABSTRACT Catheter-associated urinary tract infections are biofilm-mediated infections that cause a significant economic and health burden in nosocomial environments. Using a newly developed murine model of this type of infection, we investigated the role of fimbriae in implant-associated urinary tract infections by the Gram-negative bacterium Klebsiella pneumoniae, which is a proficient biofilm former and a commonly isolated nosocomial pathogen. Studies have shown that type 1 and type 3 fimbriae are involved in attachment and biofilm formation in vitro, and these fimbrial types are suspected to be important virulence factors during infection. To test this hypothesis, the virulence of fimbrial mutants was assessed in independent challenges in which mouse bladders were inoculated with the wild type or a fimbrial mutant and in coinfection studies in which the wild type and fimbrial mutants were inoculated together to assess the results of a direct competition in the urinary tract. Using these experiments, we were able to show that both fimbrial types serve to enhance colonization and persistence. Additionally, a double mutant had an additive colonization defect under some conditions, indicating that both fimbrial types have unique roles in the attachment and persistence in the bladder and on the implant itself. All of these mutants were outcompeted by the wild type in coinfection experiments. Using these methods, we are able to show that type 1 and type 3 fimbriae are important colonization factors in the murine urinary tract when an implanted silicone tube is present.
Detectable IL-8 and IL-10 in Bronchoalveolar Lavage Fluid from Preterm Infants Ventilated for Respiratory Distress Syndrome

Pro-inflammatory cytokines such as IL-8 play an important role in the inflammatory response to neonatal airway injury. Difficulty in detecting counter-regulatory cytokines such as IL-10 in lavage fluid from preterm infants led to the suggestion that its deficit may be a factor in the etiology of chronic lung disease of prematurity (CLD). The aim of the study was to determine IL-8 and IL-10 concentrations in lavage fluid from preterm infants ventilated for respiratory distress syndrome. Fifty infants <30 wk gestation were studied who had been randomized to receive a natural or synthetic surfactant. Lavage samples were collected daily for the first week and twice weekly thereafter. Samples were immediately centrifuged and stored at −70°C. Cytokine concentrations were quantified in duplicate using commercially available sandwich ELISA kits. Lavage IL-10 concentration, at a minimum initially, rose significant over the first five postnatal days (p = 0.009). In the same samples, lavage IL-8 concentrations rose significantly over the first postnatal week (p < 0.001), the rise preceding that of IL-10. Infants dying or developing CLD had a significant early rise in both cytokine concentrations. Compared with infants developing CLD, lavage IL-10 concentrations were significantly higher on d 1 among those not developing CLD but significantly lower on d 4 (p < 0.05). To conclude, IL-10 is detectable in lavage fluid from ventilated preterm infants and its concentrations rise significantly over the first five postnatal days. In the same samples, IL-8 concentration also rises and this increase precedes the rise in IL-10.
Stereopsis in patients with albinism: clinical correlates.

PURPOSE A hallmark of albinism is excessive decussation of retinostriate projections at the optic chiasm. This misprojection might lead to abnormalities in the retinal correspondence and may account for the usual absence of stereovision. We report on 2 groups of patients with albinism who have either fine or gross stereopsis and compare the clinical findings of these groups to other patients with albinism with similar visual acuities but no stereopsis. METHODS A retrospective chart review of patients with albinism was used to segregate those with a letter visual acuity of 20/100 or better in one eye, assessment of stereopsis, and strabismus < or = 10 PD. Forty-five patients were identified. Albinism type, best-corrected visual acuity, motility, Titmus vectograph stereoacuity, iris and macula transparency grades, and the presence or absence of both melanin and an annular reflex in the macula were tabulated. A comparison of the clinical characteristics of the groups with and without stereopsis was made. RESULTS Those albino subjects who demonstrated stereopsis had better visual acuity, less iris transillumination, more frequent presence of melanin in the macula, less nystagmus, and less marked foveal hypoplasia than the albino subjects without stereopsis. No nystagmus was clinically detected in 5 patients with fine stereopsis. All these differences were statistically significant. Macular transparency grade was not significantly different between the groups. CONCLUSIONS Patients with albinism who demonstrate stereopsis tend to have better visual acuity, more iris pigment, and more melanin pigment in the macula than their counterparts without stereopsis.
Chromosomal Instability Substantiates Poor Prognosis in Patients with Diffuse Large B-cell Lymphoma

Purpose: The specific role of chromosomal instability (CIN) in tumorigenesis has been a matter of conjecture. In part, this is due to the challenge of directly observing chromosome mis-segregation events as well as the inability to distinguish the role of CIN, which consists of increased rates of chromosome mis-segregation, from that of aneuploidy, which is a state of nondiploid chromosome number. Experimental Design: Here, we examine the contribution of CIN to the prognosis of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) by directly surveying tumor cells, fixed while undergoing anaphase, for evidence of chromosome mis-segregation. Hematoxylin and eosin–stained samples from a cohort of 54 patients were used to examine the relationship between frequencies of chromosome mis-segregation and patient prognosis, overall survival, and response to treatment. Results: We show that a two-fold increase in the frequency of chromosome mis-segregation led to a 24% decrease in overall survival and 48% decrease in relapse-free survival after treatment. The HR of death in patients with increased chromosome mis-segregation was 2.31 and these patients were more likely to present with higher tumor stage, exhibit tumor bone marrow involvement, and receive a higher International Prognostic Index score. Conclusions: Increased rates of chromosome mis-segregation in DLBCL substantiate inferior outcome and poor prognosis. This is likely due to increased heterogeneity of tumor cells leading to a larger predilection for adaptation in response to external pressures such as metastasis and drug treatments. We propose that targeting CIN would yield superior prognosis and improved response to chemotherapeutic drugs. Clin Cancer Res; 17(24); 7704–11. ©2011 AACR.
Calmodulin Modulation of Single Sarcoplasmic Reticulum Ca2+‐Release Channels From Cardiac and Skeletal Muscle

Sarcoplasmic reticulum (SR) contains a Ca2+-conducting channel that is believed to play a central role in excitation-contraction coupling by releasing the Ca2+ necessary for muscle contraction. The effects of calmodulin on single cardiac and skeletal muscle SR Ca2+-release channels were studied using the planar lipid bilayer-vesicle fusion technique. Calmodulin inhibited Ca2+-release channel opening by reducing the mean duration of single-channel open events without having an effect on single-channel conductance. Inhibition by calmodulin was dependent on Ca2+ concentration and occurred in the absence of ATP. The effects of calmodulin were reversed by mastoparan, a calmodulin-binding peptide. Two other calmodulin antagonists [calmidazolium and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] modified the gating behavior of the channel in the absence of exogenous calmodulin in a concentration- and Ca2+-dependent manner. Our results suggest that calmodulin can modulate excitation-contraction coupling by directly interacting with the SR Ca2+-release channel of cardiac and skeletal muscle.
Losartan Reduces the Increased Participation of Cyclooxygenase-2-Derived Products in Vascular Responses of Hypertensive Rats

This study analyzes the role of angiotensin II (Ang II), via AT1 receptors, in the involvement of cyclooxygenase (COX)-2-derived prostanoids in phenylephrine responses in normotensive rats (Wistar Kyoto; WKY) and spontaneously hypertensive rats (SHR). Aorta from rats untreated or treated for 12 weeks with losartan (15 mg/kg · day) or hydralazine plus hydrochlorothiazide (44 and 9.4 mg/kg · day, respectively) and vascular smooth muscle cells (VSMC) from SHR were used. Vascular reactivity was analyzed by isometric recording; COX-2 expression by Western blot and reverse transcription-polymerase chain reaction; prostaglandin (PG)I2, PGF2α, 8-isoprostane, and total antioxidant status (TAS) by commercial kits; superoxide anion (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{O}_{2}^{{\bar{{\cdot}}}}\) \end{document}) by lucigenin chemiluminescence; and plasmatic malondialdehyde (MDA) by thiobarbituric acid assay. The COX-2 inhibitor N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methane sulfonamide (NS-398) at 1 μM reduced phenylephrine responses more in SHR than in WKY rats. COX-2 protein and mRNA expressions, PGF2α, PGI2, 8-isoprostane, and \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{O}_{2}^{{\bar{{\cdot}}}}\) \end{document} production, and MDA levels were higher in SHR, but TAS was similar in both strains. Losartan, but not hydralazine-hydrochlorothiazide treatment, reduced COX-2 expression and the effect of NS-398 on phenylephrine responses in SHR. Losartan also increased TAS and reduced PGF2α, PGI2, 8-isoprostane, and \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{O}_{2}^{{\bar{{\cdot}}}}\) \end{document} production and MDA levels in SHR. Ang II (0.1 μM) induced COX-2 expression in VSMC from SHR that was reduced by 30 μM apocynin and 100 μM allopurinol, NADPH oxidase, and xanthine oxidase inhibitors, respectively. In conclusion, AT1 receptor activation by Ang II could be involved in the increased participation of COX-2-derived contractile prostanoids in vasoconstriction to phenylephrine with hypertension, probably through COX-2 expression regulation. The increased oxidative stress seems to be one of the mechanisms involved.
Catecholamines Are Present in a Synaptic‐Like Microvesicle‐Enriched Fraction from Bovine Adrenal Medulla

Abstract: “Synaptic‐like microvesicles” are present in all neuroendocrine cells and cell lines. Despite their resemblance to small synaptic vesicles of the CNS. a thorough biochemical characterization is lacking. Moreover, the subcellular distribution of synaptophysin, the most abundant integral membrane protein of small synaptic vesicles, in adrenal medulla is still controversial. Using gradient centrifugation. we were able to compare the distribution of several markers for small synaptic vesicles and chromaffin granules. Synaptophysin was found at a high density (1.16 g/ml), purifying away from dopamine β‐hydroxylase and cytochrome b561. Both noradrenaline and adrenaline showed a parallel distribution with synaptophysin, suggesting their presence in synaptic‐like microvesicles. Experiments in the presence of tetrabenazine did not influence the catecholamine content. Additionally, tetrabenazine binding showed a consistent shoulder in the region of synaptophysin. [3H]‐Noradrenaline uptake was blocked by tetrabenazine, but not by desipramine. Also chromogranin A parallels the distribution of synaptophysin: however, a localization in the Golgi cannot be ruled out. Synaptophysin was shown to undergo very fast phosphorylation, together with another triplet protein of ∼ 18 kDa. In contrast, the latter showed a rather bimodal distribution coinciding with synaptophysin and dopamine β‐hydroxylase. Immunoelectron microscopy of synaptic‐like microvesicle fractions showed an intense labeling for synaptophysin on 60‐90‐nm organelles. Whereas abundant gold labeling for cytochrome b561 was found over the entire surface of chromaffin granules, synaptophysin labeling was encountered mostly on vesicles adsorbed to granules. We conclude that catecholamines might be stored in synaptic‐like microvesicles of the chromaffin cell.
DNA Double-Strand Break Repair as Determinant of Cellular Radiosensitivity to Killing and Target in Radiation Therapy

Radiation therapy plays an important role in the management of a wide range of cancers. Besides innovations in the physical application of radiation dose, radiation therapy is likely to benefit from novel approaches exploiting differences in radiation response between normal and tumor cells. While ionizing radiation induces a variety of DNA lesions, including base damages and single-strand breaks, the DNA double-strand break (DSB) is widely considered as the lesion responsible not only for the aimed cell killing of tumor cells, but also for the general genomic instability that leads to the development of secondary cancers among normal cells. Homologous recombination repair (HRR), non-homologous end-joining (NHEJ), and alternative NHEJ, operating as a backup, are the major pathways utilized by cells for the processing of DSBs. Therefore, their function represents a major mechanism of radiation resistance in tumor cells. HRR is also required to overcome replication stress – a potent contributor to genomic instability that fuels cancer development. HRR and alternative NHEJ show strong cell-cycle dependency and are likely to benefit from radiation therapy mediated redistribution of tumor cells throughout the cell-cycle. Moreover, the synthetic lethality phenotype documented between HRR deficiency and PARP inhibition has opened new avenues for targeted therapies. These observations make HRR a particularly intriguing target for treatments aiming to improve the efficacy of radiation therapy. Here, we briefly describe the major pathways of DSB repair and review their possible contribution to cancer cell radioresistance. Finally, we discuss promising alternatives for targeting DSB repair to improve radiation therapy and cancer treatment.
Expression and localization of urokinase-type plasminogen activator receptor in bovine cumulus–oocyte complexes

Summary Urokinase-type plasminogen activator (uPA) is a serine protease involved in extracellular matrix remodeling through plasmin generation. uPA usually binds to its receptor, uPAR, which is anchored to the plasma membrane through a glycosylphosphatidylinositol anchor. uPA/uPAR binding increases proteolytic activity in the neighborhood of the cells containing uPAR and activates intracellular signaling pathways involved in extracellular matrix remodeling, cell migration and proliferation. The aim of this work was to study the expression of uPA, uPAR and plasminogen activator inhibitor-1 (PAI-1) in immature and in vitro matured bovine cumulus–oocyte complexes (COCs). uPA is only expressed in the cumulus cells of immature and in vitro matured COCs, while uPAR and PAI-1 are expressed in both the cumulus cells and the immature and in vitro matured oocytes. In addition, uPAR protein was localized by confocal microscopy in the plasma membrane of oocytes and cumulus cells of immature COCs. Results from this research led us to hypothesize that the uPA/uPAR interaction could cause the local production of uPA-mediated plasmin over oocyte and cumulus cell surface; plasmin formation could also be regulated by PAI-1.
[The effects of tumor antigen gene OVA66 on biological characteristics of tumor cells].

AIM To explore the effects of tumor antigen gene OVA66 on the biological characteristics of tumor cells. METHODS The eukaryotic expression vector pcDNA3.1-mock and recombined vector pcDNA3.1-OVA66 were transfected into hepatoma cell line SMMC-7721 by LipofectAMINETM 2000. After stable selection and clone proliferation of cells, the expression of OVA66 gene and protein was detected by RT-PCR, Western blot and immunocytochemical (ICC) staining. The cell growth cycle was analyzed by FACS. The ultrastructure was observed under electron microscope. The experiments in cell migration and invasion were performed in vitro. The OVA66-associated genes were analyzed by genechip technique after gene transfection. RESULTS OVA66 was highly expressed in 7721 cells transfected with pcDNA3.1-OVA66 at mRNA level. Western blot result demonstrated that OVA66 protein content was notably increased compared with that in control cells. Electron microscope and FACS results indicated that OVA66 gene promoted the growth and proliferation of tumor cells. In vitro, the experiments in cell migration and invasion showed that this gene enhanced migration and invasion of tumor cells. The result of genechip demonstrated that the over- expression of OVA66 gene increased the expression of plasminogen activator inhibitor-1 gene (PAI-1), suggesting that it had some effects on tumor invasion and metastasis. CONCLUSION Tumor antigen gene OVA66 and it's protein demonstrate a series of biological characteristics of tumor cells, which can promote the proliferation, migration and invasion of tumor cells.
Co‐expression of epidermal growth factor receptor and transforming growth factor‐α predicts worse prognosis in breast‐cancer patients

Epidermal growth factor receptor (EGF‐R) and its ligand, transforming growth factor‐α (TGF‐α), play an important role through the autocrine growth‐regulation system in several human cancers, including breast cancer. However, the clinical significance of co‐expression of EGF‐R and TGF‐α has not been elucidated. One hundred seventy‐three female patients diagnosed as invasive ductal carcinoma who had undergone a mastectomy (159 patients) or breast‐conserving surgery (14 patients) were followed up for 81 to 119 months (median 94 months) post‐operatively. Immunoreactivity for EGF‐R, TGF‐α, p53 and c‐erbB‐2 with paraffin‐embedded carcinoma tissue was investigated using labeled streptavidin‐biotin methods. Positive rates of carcinoma cells were 27%, 33%, 32% and 26% for EGF‐R, TGF‐α, p53 and c‐erbB‐2, respectively. Expression of EGF‐R only was observed in 16% (28/173), of TGF‐α only in 22% (38/173), of both EGF‐R and TGF‐α in 11% (19/173) and of neither in 51% (88/173). By univariate analysis, significant differences in overall survival and disease‐free survival were noted according to the co‐expression of EGF‐R and TGF‐α (p < 0.0001, p < 0.0001), co‐expression of EGF‐R and c‐erbB‐2 (p = 0.0029, p = 0.0028), nodal status (p = 0.0028, p = 0.0001), tumor size (p = 0.0001, p < 0.0001) and c‐erbB‐2 expression (p = 0.0034, p = 0.018), respectively. The status of p53 expression (p = 0.01), estrogen receptor (p = 0.042) and progesterone receptor (p = 0.046) showed significant differences in overall survival. According to Cox's multivariate analysis, co‐expression of EGF‐R and TGF‐α had the most significant effect on disease‐free survival (p < 0.0001) and overall survival (p < 0.0001), followed by nodal status. Co‐expression of EGF‐R and TGF‐α by immunohistochemical detection is an independent prognostic indicator, and it may be helpful for determining the group of breast‐cancer patients with an aggressive phenotype. Int. J. Cancer 89:484–487, 2000. © 2000 Wiley‐Liss, Inc.