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Biomedical subjects

Linda Wang

Publications and source records attributed to Linda Wang.

At least 19 recordsLinked to original sources
PubMed2026

Assessment of Genetic Correlations Between Tobacco or Alcohol Use and Neurodegenerative Diseases Using East Asian Genetic Ancestry Genome-Wide Association Study Results.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.

Female↗
PubMed2006

Effect of the number of coats of simplified adhesive systems on microleakage of dentin-bordered composite restorations.

AIM: This study tested the null hypothesis that there is no difference on microleakage of dentin-bordered composite restorations using single or double coats of adhesive from one-bottle adhesive systems. METHODS AND MATERIALS: The enamel surface was removed from freshly extracted bovine teeth, and standardized Class V cavities (3 x 3 x 1.5 mm) were made at the cervical areas of buccal surfaces. Teeth were restored and grouped according to type of adhesive systems [Prime Bond 2.1 (PB2.1), Prime & Bond NT (PBNT), and Single Bond (SB)] and to the number of coats (one or two) to be used. The restorations were polished and immersed in a 0.5% aqueous solution of basic fuchsin for four hours. Teeth were then sectioned and the most infiltrated section of each tooth was selected under magnification, scanned, and quantitatively analyzed using a computer program. Data were analyzed using two-way analysis of variance (ANOVA) and Student-Newman-Keuls (a=0.05). RESULTS: Groups without filler content (PB2.1 and SB) showed no difference in microleakage using single or double coats. However, PBNT (with nanofiller) showed statistically less microleakage when only one coat was applied. The influence of the number of coats of the adhesive systems on dentin margin microleakage was material dependent. CONCLUSION: All adhesive systems demonstrated microleakage, however, it could be minimized using two coats of non-filled or one coat of a filled adhesive system.

Acetone↗
PubMed2006

Water sorption and solubility of dentin bonding agents light-cured with different light sources.

OBJECTIVE: The aim of this study was to compare water sorption (WS) and solubility (WSB) of different dentin bonding agents (DBA) as regards classification and light-activation system. The null hypotheses were: (1) there is no difference among DBA with respect to water sorption and solubility; (2) there is no effect of light-curing source on water sorption and solubility of DBA. METHODS: The tested materials were: three-step etch-and-rinse (ScotchBond multi-purpose and Heliobond-control groups), two-step etch-and-rinse (Excite, Adper Single Bond, Adper Single Bond 2), self-etching (Adhse) and all-in-one (Xeno III) systems. For each material, six specimens were prepared (0.8mmx5.5mm) for each light-activation device: halogen lamp (control) or light-emitting diodes (LED). They were transferred to desiccators until a constant mass was obtained (m(1)), subsequently immersed in deionized water until no alteration was obtained (m(2)). Following, the specimens were reconditioned to constant mass in desiccators (m(3)). The volume (V) of each specimen was calculated (mm(3)). WS and WSB were determined using the equations (m(2)-m(3)/V) and (m(3)-m(1)/V), respectively. Data were subjected to one-way analysis of variance and Tukey test (p<0.05). The influence of photo-activation units was analyzed by t-test. RESULTS: Higher values of WS and WSB were observed for the two-step etch-and-rinse and all-in-one systems. The employed light-activation unit also affected the tested characteristics. Thus, the anticipated null hypotheses were rejected. CONCLUSIONS: Simplified systems were more susceptible to water adverse and they may become more prone to degradation over time regardless of the type of light-activation source.

Absorption↗
PubMed2006

Flaxseed and its components reduce metastasis after surgical excision of solid human breast tumor in nude mice.

This study determined the effect of 10% flaxseed (FS) and its components, secoisolariciresinol diglycoside (SDG) and flaxseed oil (FO) alone or in combination (SDG+FO), on the metastasis and recurrence of human breast tumor after excision in nude mice. Mice were injected orthotopically with human breast cancer cells (MDA-MB-435) and fed basal diet (BD). When the tumors reached an average size of 110 mm(2) (0.9 g), surgical excisions were performed, and the mice were assigned to one of five diet groups for 7 weeks. The total incidence of metastasis was significantly lower in the FS, SDG, and SDG+FO groups. Reduced lung and lymph node metastases were observed in the FS and SDG+FO groups. In the FS and FO groups, a greater reduction in lung and total metastases was found when excised tumors were 0.9 g. There was no significant difference in tumor recurrence among groups. In conclusion, FS and its components inhibited tumor metastasis but not tumor recurrence after surgical excision of the primary tumor.

Animals↗
PubMed2006

Bond strength of resin-based restorations polymerized with different light-curing sources.

PURPOSE: To evaluate the influence of different light-curing units on microtensile bond strength of resin composite restorations. MATERIALS AND METHODS: Standardized Class I preparations (6.0 x 4.5 mm, 2.5 mm deep) were made in extracted human third molars after abrading the cusps. Resin was inserted in bulk using a 3M ESPE restorative system [Adper Single Bond (DBA)/ Filtek Z250 (RC)]. Both materials were polymerized using different light-curing units: QTH at 540 mW/cm(2) (XL 3000, 3M ESPE); LED at 750 mW/cm(2) (Elipar FreeLight2, 3M ESPE); PAC at 2130 mW/cm(2) (Arc Light II, Air Techniques). Nine different light combinations were developed to polymerize both DBA and RC: QTH/QTH; QTH/LED; QTH/PAC; LED/LED; LED/QTH; LED/PAC; PAC/PAC; PAC/QTH; PAC/LED. Restored teeth were stored in distilled water for 24 h at 37 degrees C and then sectioned, yielding stick-shaped specimens with a bonded area of approximately 0.9 mm(2). Specimens were assessed in a testing machine at a crosshead speed of 1 mm/min. The results were analyzed using two-way ANOVA and Tukey's test at a pre-set alpha = 0.05. RESULTS: The combinations PAC/QTH and QTH/QTH presented the highest bond strength values, and LED/QTH the lowest (p < 0.05). Significantly lower values were observed in combinations when the LED light was used to polymerize DBA compared to QTH and PAC lights, irrespective of the light source used to polymerize RC (p < 0.05). Same light combinations presented similar bond strength values. CONCLUSIONS: Different light sources influence restoration bond strength. Bond strength is more dependent on the light source used for DBA than for curing RC.

Bisphenol A-Glycidyl Methacrylate↗
PubMed2005

The inhibitory effect of flaxseed on the growth and metastasis of estrogen receptor negative human breast cancer xenograftsis attributed to both its lignan and oil components.

Our previous studies have shown that dietary flaxseed (FS) can reduce the growth and metastasis of human estrogen receptor negative (ER-) breast cancer in nude mice. The aims of our study were to determine (i) whether the tumor inhibitory effect of FS was due to its oil (FO), lignan secoisolariciresinol diglycoside (SDG), or both components, and (ii) whether the effect on tumor growth was related to increased lipid peroxidation. Athymic nude mice were orthotopically injected with ER- breast cancer cells (MDA-MB-435) and 8 weeks later were fed either the basal diet (BD) or BD supplemented with 10% FS, SDG, FO, or combined SDG and FO (SDG + FO) for 6 weeks. The SDG and FO levels were equivalent to the amounts in the 10% FS. Compared to the BD group, the tumor growth rate was significantly lower (p < 0.05) in the FS, FO, and SDG + FO groups, in concordance with decreased cell proliferation and increased apoptosis; however, these did not significantly relate to the lipid peroxidation, indexed as malonaldehyde (MDA), in the primary tumors. Lung metastasis incidence was reduced (16-70%) by all treatments, significantly in the FS and SDG + FO groups. The distant lymph node metastasis was significantly decreased (52%) only in the FO group. Although the total metastasis incidence was lowered (42%) significantly only in the SDG + FO group, all treatment groups did not differ significantly. In conclusion, FS reduced the growth and metastasis of established ER- human breast cancer in part due to its lignan and FO components, and not to lipid peroxidation.

Animals↗
PubMed2005

Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations.

Mutations in the PTEN-induced kinase 1 (PINK1) gene have recently been implicated in autosomal recessive early onset Parkinson Disease (1, 2). To investigate the role of PINK1 in neurodegeneration, we designed human and murine neuronal cell lines expressing either wild-type PINK1 or PINK1 bearing a mutation associated with Parkinson Disease. We show that under basal and staurosporine-induced conditions, the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells was lower in wild-type PINK1 expressing SH-SY5Y cells than in mock-transfected cells. This phenotype was due to a PINK1-mediated reduction in cytochrome c release from mitochondria, which prevents subsequent caspase-3 activation. We show that overexpression of wild-type PINK1 strongly reduced both basal and staurosporine-induced caspase 3 activity. Overexpression of wild-type PINK1 also reduced the levels of cleaved caspase-9, caspase-3, caspase-7, and activated poly(ADP-ribose) polymerase under both basal and staurosporine-induced conditions. In contrast, Parkinson disease-related mutations and a kinase-inactive mutation in PINK1 abrogated the protective effect of PINK1. Together, these results suggest that PINK1 reduces the basal neuronal pro-apoptotic activity and protects neurons from staurosporine-induced apoptosis. Loss of this protective function may therefore underlie the degeneration of nigral dopaminergic neurons in patients with PINK1 mutations.

Aged↗
PubMed2004

Evaluation of the roughness and mass loss of the flowable composites after simulated toothbrushing abrasion.

The purpose of this study was to measure mass loss and surface roughness changes of different brands of flowable resin composites after a simulated toothbrushing test. The null hypotheses were that there would be no differences in mass loss and no significant changes in surface roughness after this test and that there would be no correlation between the two variables. The tested materials were Aeliteflo (Bisco), Flow-It (Pentron), Flow-It LF (Pentron), Natural Flow (DFL) and Wave (SDI). Z100 (3M/ESPE) microhybrid and Silux Plus (3M/ESPE) microfilled resin composites were used as control materials. Twelve specimens (5 mm in diameter, 3 mm thick) of each material were prepared according to manufacturers' instructions. Toothbrushing abrasion was performed on all specimens from each of the materials using a simulator. The percentage mass loss and surface roughness were assessed before and after 100,000 brushstrokes, using a Sartorius analytical balance of 0.0001 g accuracy and a Hommel Tester T1000, respectively. The measurements of both properties were statistically compared by paired t-test and Tukey's test (p < 0.05). All materials presented a statistically significant mass loss comparing initial and final values, with the exception of Flow-It LF. However, no difference was revealed when comparing the mass loss of the different tested materials. All materials became rougher and Wave presented statistically higher roughness compared to the other resin composites. Flowable resin composites did not seem to be superior to the control groups, and they can be expected to wear by mass loss and to have an increased roughness of surface after toothbrushing action. The anticipated null hypotheses were partially accepted.

Composite Resins↗
PubMed2004

A toll-like receptor-based two-hybrid assay for detecting protein--protein interactions on live eukaryotic cells.

Protein--protein interactions underly diverse biological processes. Here, we describe a method for detecting protein interactions on the cell surface. This method is based on the mechanism of TLR2 activation whereby extracellular (EC) domain-mediated heterodimerization of TLR2 and TLR1 activates NF-kappaB and other signalling processes. Test proteins were expressed as the EC domains of TLR1 and TLR2 in fusion with the transmembrane/cytoplasmic (TM/Cyt) domains, i.e. tmTIR1 and tmTIR2. The feasibility of this TIR1/2-based method was examined by expression of IL-4 and the EC domains of the interleukin-4 receptor alpha (IL-4Ralpha) and the cytokine receptor common gamma chain (gammaC) as hybrid receptors with tmTIR1 and tmTIR2. Upon co-expression of IL4Ralpha-TIR1 and gammaC-TIR2 in 293T cells, NF-kappaB activation was found to be inducible by IL-4. Co-expression of IL4-TIR1 with IL4Ralpha-TIR2, but not gammaC-TIR2, led to constitutive NF-kappaB activation. This is consistent with IL-4 primarily binding to IL4Ralpha but not gammaC. Co-expression of the IL4Ralpha-TIR1/2, IL4-TIR1/2 or gammaC-TIR1/2 hybrid receptor pairs also constitutively activated NF-kappaB suggesting that IL-4, IL4Ralpha and gammaC form homodimers or homotypic interactions. This was confirmed by immunoprecipitation studies. In summary, we report a TIR1/2-based assay for detecting interactions between membrane proteins, receptors/ligands and secreted proteins on live eukaryotic cells.

Cell Line↗
PubMed2004

Wear resistance of packable resin composites after simulated toothbrushing test.

PURPOSE: The purpose of this study was to determine the wear resistance of five different packable composites versus two different composite controls using a laboratory toothbrushing simulation test. MATERIALS AND METHODS: Twelve samples measuring 5 mm in diameter and 3 mm thick were prepared from the following resin composites: Packable resin composites SureFil (Dentsply Ind. Com. Ltda, Petrópolis, Rio de Janeiro, Brazil), Alert (Jeneric Pentron Incorporated, Wallingford, CT, USA), Filtek P60 (3M ESPE Dental Products, St. Paul, MN, USA), Prodigy Condensable (sds Kerr, Orange CA, USA), Solitaire (Heraeus Kulzer GmbH, Wehrheim, Germany), and control resin composites Z100 Restorative (3M ESPE) and Silux Plus (3M ESPE). Finishing and polishing were conducted with Sof-Lex disks (3M ESPE), and baseline weight (grams) and surface roughness (measured with Hommel Tester T 1000, Hommelwerke, GmbH, Alte Tuttinger Strebe 20. D-7730 VS-Schwenningen, Germany) were recorded. Specimens were aged for 2 weeks until they reached a weight that remained constant for 5 consecutive days, and then were subjected to 100,000 cycles of brushing (representative of 4.2 yr) using a toothbrushing testing machine. Toothbrush heads with soft bristle tips (Colgate Classic, Colgate-Palmolive Co., Osasco, São Paulo, Brazil) with dentifrice suspension (Colgate MFP, Colgate-Palmolive Co.) in deionized water were used under a 200 g load. Changes in weight and surface roughness were determined after toothbrushing cycles. RESULTS: Significant differences of weight loss and surface roughness were found (paired t-test, p < .05). Weight loss percentage (mean [SD]) ranged from 0.38 to 1.69% (analysis of variance and Tukey's least significant difference, p < .05); the weight loss of the materials ranked from least to most as follows: SureFil (0.38 [0.56]), Alert (0.52 [0.18]), Z100 (1.16 [0.27]), Filtek P60 (1.31 [0.17]), Solitaire (1.51 [0.45]), Prodigy Condensable (1.55 [0.471), and Silux Plus (1.69 [0.66]). Regarding surface roughness, Prodigy Condensable (0.19 [0.08]), Solitaire (0.28 [0.06]), and Z100 (0.30 [0.07]) became less rough after toothbrushing, whereas all the others were rendered rougher: Alert (0.49 [0.29]), Filtek P60 (0.28 [0.08]), Silux Plus (0.39 [0.091), and SureFil (0.81 [0.32]). CONCLUSION: SureFil and Alert were statistically more resistant to wear (less weight loss) than were the other materials. SureFil became significantly rougher than did all the others. CLINICAL SIGNIFICANCE: Overal, packable resin composites are unlikely to show superior wear resistance with regard to weight loss and surface roughness compared with current resin composites also indicated for posterior restorations.

Analysis of Variance↗
PubMed2003

Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain.

The presenilins and nicastrin form high molecular mass, multimeric protein complexes involved in the intramembranous proteolysis of several proteins. Post-translational glycosylation and trafficking of nicastrin is necessary for the activity of these complexes. We report here that although there are differences in the post-translational processing of nicastrin in neurons and glia, both of the presenilins are required for the physiological post-translational modification and for the correct subcellular distribution of nicastrin. Absence of presenilin 1 (PS1) is associated with dramatic reductions in the level of mature glycosylated nicastrin and with redistribution of nicastrin away from the cell surface. In contrast, absence of presenilin 2 (PS2) is associated with only modest reductions in the levels of immature nicastrin. It is notable that these differential effects parallel the differential effects of null mutations in PS1 and PS2 on APP and Notch processing. Our data therefore suggest that the differential interactions of PS1 and PS2 with nicastrin reflect different functions for the PS1 and PS2 complexes.

Amyloid Precursor Protein Secretases↗
PubMed2003

Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles.

Elevated levels of p25 and constitutive activation of CDK5 have been observed in AD brains. This has led to the hypothesis that increased p25 levels could promote neurofibrillary tangles (NFT) through CDK5-mediated hyperphosphorylation of tau, the principal component of NFTs. We examined p25 immunoreactivity in brains from sporadic and familial AD cases, as well as other neurologic diseases that exhibit NFT, such as Down's syndrome (DS), Pick's disease (Pick), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD). Neither the p25 immunoreactivity nor the p25/p35 ratio was elevated in the AD brains or in the other tauopathies (n = 34) compared with controls (n = 11). Although Abeta peptides have been suggested to activate calpain-mediated cleavage of p35 to p25 in cultured neurons, p25 levels in brains of TgCRND8 mice, which express high levels of brain Abeta peptides, were similar to those of non-Tg littermates. Our data suggest that high Abeta levels in brain do not activate p35 proteolysis, and p25 is unlikely to be a causative agent for NFT formation in AD or other tauopathies.

Adult↗
PubMed2002

Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts.

Angiogenesis is important in tumor growth, progression and metastatic dissemination. Vascular endothelial growth factor (VEGF) is one key factor in promotion of breast cancer angiogenesis. VEGFs are bioactive in the extracellular space where they become available to the endothelial cells. Phytoestrogens such as lignans have been shown to alter breast cancer incidence and be cancer-protective in rats. We show that supplementation of 10% flaxseed, the richest source of mammalian lignans, to nude mice with established human breast tumors reduced tumor growth and metastasis. Moreover, flaxseed decreased extracellular levels of VEGF, which may be one mechanistic explanation to the decreased tumor growth and metastasis.

Animals↗