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1.
Cancers (Basel) ; 16(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38254878

RESUMO

Galactosylceramide (GalCer) increases the resistance of breast cancer cells to doxorubicin, paclitaxel, and cisplatin by acting as an anti-apoptotic molecule. GalCer was found to specifically downregulate the levels of the pro-apoptotic TNFRSF1B and TNFRSF9 genes and upregulate the levels of the anti-apoptotic BCL2 gene, suggesting that this glycosphingolipid regulates their expression at the transcriptional level. Consistent with this hypothesis, MDA-MB-231 and MCF7 breast cancer cells with high levels of GalCer showed lower activity of the TNFRSF1B and TNFRSF9 promoters than cells lacking GalCer. In contrast, the activity of the BCL2 promoter was higher in MCF7 cells overproducing GalCer than in MCF7 cells without GalCer. However, no difference in BCL2 promoter activity was observed between MDA-MB-231 cells with high and no GalCer content. Instead, we found that high levels of GalCer increased the stability of Bcl-2 mRNA. Subsequent studies showed that breast cancer cells with high levels of GalCer are characterized by significantly lower expression of P53. Importantly, inhibition of P53 expression by siRNA in MCF7 and MDA-MB-231 cells lacking GalCer resulted in decreased expression and promoter activity of the TNFRS1B and TNFRSF9 genes. On the other hand, increased expression and promoter activity of the BCL2 gene was found in such MCF7 cells, and increased stability of Bcl-2 transcripts was observed in such MDA-MB-231 cells. Taken together, these data strongly suggest that the regulatory protein that simultaneously increases the expression of the TNFRSF1B and TNFRSF9 genes and decreases the expression of the BCL2 gene and the stability of Bcl-2 transcripts is most likely P53, the expression of which is GalCer dependent.

2.
J Aging Stud ; 67: 101188, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38012947

RESUMO

There is increasing interest across European contexts in promoting active social lives in older age, and counteracting pathways and outcomes related to social isolation and loneliness for men and women in later life. This is evidenced within national and European level policy, including the 2021 Green Paper on Ageing and its concern with understanding how risks can accrue for European ageing populations in the relational sphere. Research indicates that life-course transitions can function as a source of these risks, leading to a range of potentially exclusionary impacts for the social relations of older men and women. Findings presented in this paper are drawn from the qualitative component of a larger European mixed-methods study on exclusion from social relations (GENPATH: A life course perspective on the GENdered PATHways of social exclusion in later life, and its consequences for health and well-being). We use data from 119 in-depth interviews from four jurisdictions: Austria, Czechia, Ireland and Spain. This research employed an approach that focused on capturing lived experienced insights related to relational change across the life course, the implications of these changes for multifaceted forms of exclusion from social relations and the role of gender in patterning these changes and implications. We focused on transitions that commonly emerged across those jurisdictions for older people: onset of ill-health, bereavement, retirement and relocation. We found that these transitions translate into multidimensional experiences of exclusion from social relations in the lives of older men and women by constraining their social networks, support networks, social opportunities and intimate relationships.


Assuntos
Acontecimentos que Mudam a Vida , Isolamento Social , Masculino , Humanos , Feminino , Idoso , Pesquisa Qualitativa , Solidão , Envelhecimento
3.
J Aging Stud ; 65: 101137, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37268382

RESUMO

Unequal ageing patterns are increasingly prevalent within the life courses of heterogeneous older populations. Critical transitions in later life may contribute to these patterns and to more multifaceted deep-rooted forms of social exclusion. Yet despite significant research in this area, knowledge gaps remain regarding the subjective experiences of these transitions, the trajectories and constituent events of these transitions, and the related mechanisms that may drive exclusion. With a focus on lived experience, this article aims to investigate the role of critical life transitions in older age in constructing multidimensional social exclusion. The onset of dementia, bereavement of a significant other, and forced migration are selected as three illustrative transitions in older age. Based on 39 in-depth life-course interviews and life-path analyses, the study sets out to illuminate common features of the transitional process that increases exclusion susceptibility, and the potential commonalities regarding transition-related exclusionary mechanisms. Transition trajectories related to each of the transitions are first described identifying shared exclusionary risk features. Transition-related mechanisms that can generate multidimensional social exclusion are then presented as arising from a transition's nature and character, its structural and management aspects, and its symbolic and normative positioning. Findings are discussed with reference to the international literature and future conceptualisation of social exclusion in later life.


Assuntos
Envelhecimento , Isolamento Social , Humanos , Fatores de Risco , Acontecimentos que Mudam a Vida
4.
Z Gerontol Geriatr ; 56(5): 357-361, 2023 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-37322267

RESUMO

There is much to be gained from participatory research: it can increase the closeness of research to everyday life, the acceptance of the resulting practical implications and holds the potential to fundamentally democratize scientific knowledge production. It is not surprising that this is not without irritation on the part of academic researchers and their institutional environment as well as on the part of nonacademically trained co-researchers. Based on an inspection of the relevant literature this article outlines the different understanding and definitions of participatory age(ing) research, its current fields of application, and utilization in different phases of the research process. Subsequently, the challenges that participatory approaches in age(ing) research can pose in these different fields and phases are discussed and possible solutions are outlined.

5.
Int J Mol Sci ; 24(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37372998

RESUMO

B-cell leukemia/lymphoma 11A (BCL11A) may be one of the potential biomarkers of non-small cell lung cancer (NSCLC). However, its role in the development of this cancer has not yet been precisely established. The aim of this study was to investigate the expression of BCL11A at the mRNA and protein levels in NSCLC cases and non-malignant lung tissue (NMLT) and to determine the relationship between BCL11A expression and the clinicopathological factors and Ki-67, Slug, Snail and Twist. The localization and the level of BCL11A protein were examined using immunohistochemistry (IHC) on 259 cases of NSCLC, and 116 NMLT samples were prepared as tissue microarrays and using immunofluorescence (IF) in the following cell lines: NCI-H1703, A549 and IMR-90. The mRNA expression of BCL11A was determined using real-time PCR in 33 NSCLC cases, 10 NMLT samples and the cell lines. BCL11A protein expression was significantly higher in NSCLC cases compared to NMLT. Nuclear expression was found in lung squamous cell carcinoma (SCC) cells, while cytoplasmic expression was demonstrated in adenocarcinoma (AC) cells. Nuclear expression of BCL11A decreased with increasing malignancy grade and correlated positively with Ki-67 and Slug and Twist expression. The opposite relationships were found for the cytoplasmic expression of BCL11A. Nuclear expression of BCL11A in NSCLC cells may affect tumor cell proliferation and change their phenotype, thus promoting tumor progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Antígeno Ki-67/metabolismo , Fatores de Transcrição/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
7.
Sci Rep ; 13(1): 6574, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085653

RESUMO

We have previously shown that high expression of prolactin-induced protein (PIP) correlates with the response of breast cancer (BC) patients to standard adjuvant chemotherapy (doxorubicin and cyclophosphamide), which suggests that the absence of this glycoprotein is associated with resistance of tumor cells to chemotherapy. Therefore, in the present study, we analyzed the impact of PIP expression on resistance of BC cells to anti-cancer drugs and its biological role in BC progression. Expression of PIP and apoptotic genes in BC cell lines was analyzed using real-time PCR and Western blotting. PIP was detected in BC tissue specimens using immunohistochemistry. The tumorigenicity of cancer cells was analyzed by the in vivo tumor growth assay. Apoptotic cells were detected based on caspase-3 activation, Annexin V binding and TUNEL assay. The interaction of PIP with BC cells was analyzed using flow cytometry. Using two cellular models of BC (i.e. T47D cells with the knockdown of the PIP gene and MDA-MB-231 cells overexpressing PIP), we found that high expression of PIP resulted in (1) increased sensitivity of BC cells to apoptosis induced by doxorubicin (DOX), 4-hydroperoxycyclophosphamide (4-HC), and paclitaxel (PAX), and (2) improved efficacy of anti-cancer therapy with DOX in the xenograft mice model. Accordingly, a clinical study revealed that BC patients with higher PIP expression were characterized by longer 5-year overall survival and disease-free survival. Subsequent studies showed that PIP up-regulated the expression of the following pro-apoptotic genes: CRADD, DAPK1, FASLG, CD40 and BNIP2. This pro-apoptotic activity is mediated by secreted PIP and most probably involves the specific surface receptor. This study demonstrates that a high expression level of PIP sensitizes BC cells to anti-cancer drugs. Increased sensitivity to chemotherapy is the result of pro-apoptotic activity of PIP, which is evidenced by up-regulation of specific pro-apoptotic genes. As high expression of PIP significantly correlated with a better response of patients to anti-cancer drugs, this glycoprotein can be a marker for the prognostic evaluation of adjuvant chemotherapy.


Assuntos
Apoptose , Neoplasias da Mama , Animais , Feminino , Humanos , Camundongos , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Glicoproteínas/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Prolactina , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico
8.
Front Sociol ; 6: 686674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262964

RESUMO

In the institutionalized life course transition from work to retirement is the transition that culturally defines the beginning of later life. However, there is no universal way of experiencing retirement or understanding retirees' social roles. Especially in the context of the post-communist, liquid modern reality in Poland. The social role of the retiree, defined as a set of rules and expectations generated for individuals occupying particular positions in the social structure, is constructed at the intersection of what is culturally defined and individually negotiated. Therefore, the way in which individuals (re)define term "retiree" and "do retirement" reflects not only inequalities in individual resources and attitudes, but also in social structure in a given place and at a given time. In this contribution, I draw upon data from 68 qualitative interviews with retirees from Poland to analyze retirement practices and meanings assigned to the term "retiree." Applying practice theory, I explore the inequalities they (re)produce, mirror and reinforce at the same time. Results show that there are four broad types of retirement practices: caregiving, working, exploring and disengaging. During analysis of meanings assigned by participants to the term "retiree," two definitions emerged: one of a "new wave retiree" and the other of a "stagnant retiree." Results suggest that in the post-communist context, retirement practices and meanings assigned to the term "retiree" are in the ongoing process of (re)negotiation and are influenced on the one hand by the activation demands resulting from discourses of active and productive aging, and on the other by habitus and imaginaries of retirement formed in the bygone communist era. Retirement practices and definitions of the term "retiree" that emerged from the data reflect structural and individual inequalities, highlighting intersection of gender, age and socioeconomic status in the (re)production of inequalities in retirement transition in the post-communist context.

9.
Food Funct ; 12(3): 1271-1290, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33434253

RESUMO

The aim of the study was to broadly determine the biological activities of purple potato ethanolic extract of the Blue Congo variety (BCE). The antioxidant activity of BCE was determined in relation to liposome membranes, and peroxidation was induced by UVB and AAPH. To clarify the antioxidant activity of BCE, we investigated its interactions with hydrophilic and hydrophobic regions of a membrane using fluorimetric and FTIR methods. Next, we investigated the cytotoxicity and pro-apoptotic activities of BCE in two human colon cancer cell lines (HT-29 and Caco-2) and in normal cells (IPEC-J2). In addition, the ability to inhibit enzymes that are involved in pro-inflammatory reactions was examined. Furthermore, BCE interactions with serum albumin and plasmid DNA were investigated using steady state fluorescence spectroscopy and a single molecule fluorescence technique (TCSPC-FCS). We proved that BCE effectively protects lipid membranes against the process of peroxidation and successfully inhibits the cyclooxygenase and lipoxygenase enzymes. Furthermore, it interacts with the hydrophilic and hydrophobic parts of lipid membranes as well as with albumin and plasmid DNA. It was observed that BCE is more cytotoxic against colon cancer cell lines than normal IPEC-J2 cells; it also induces apoptosis in cancer cell lines, but does not induce cell death in normal cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Solanum tuberosum/química , Albuminas , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Humanos , Lipídeos/química , Lipossomos , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Extratos Vegetais/química , Plasmídeos , Ligação Proteica , Espécies Reativas de Oxigênio , Albumina Sérica/química , Albumina Sérica/metabolismo
10.
J Biol Chem ; 296: 100299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33460651

RESUMO

The human Gb3/CD77 synthase, encoded by the A4GALT gene, is an unusually promiscuous glycosyltransferase. It synthesizes the Galα1→4Gal linkage on two different glycosphingolipids (GSLs), producing globotriaosylceramide (Gb3, CD77, Pk) and the P1 antigen. Gb3 is the major receptor for Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli. A single amino acid substitution (p.Q211E) ramps up the enzyme's promiscuity, rendering it able to attach Gal both to another Gal residue and to GalNAc, giving rise to NOR1 and NOR2 GSLs. Human Gb3/CD77 synthase was long believed to transfer Gal only to GSL acceptors, therefore its GSL products were, by default, considered the only human Stx receptors. Here, using soluble, recombinant human Gb3/CD77 synthase and p.Q211E mutein, we demonstrate that both enzymes can synthesize the P1 glycotope (terminal Galα1→4Galß1→4GlcNAc-R) on a complex type N-glycan and a synthetic N-glycoprotein (saposin D). Moreover, by transfection of CHO-Lec2 cells with vectors encoding human Gb3/CD77 synthase and its p.Q211E mutein, we demonstrate that both enzymes produce P1 glycotopes on N-glycoproteins, with the mutein exhibiting elevated activity. These P1-terminated N-glycoproteins are recognized by Stx1 but not Stx2 B subunits. Finally, cytotoxicity assays show that Stx1 can use P1 N-glycoproteins produced in CHO-Lec2 cells as functional receptors. We conclude that Stx1 can recognize and use P1 N-glycoproteins in addition to its canonical GSL receptors to enter and kill the cells, while Stx2 can use GSLs only. Collectively, these results may have important implications for our understanding of the Shiga toxin pathology.


Assuntos
Galactosiltransferases/química , Globosídeos/química , Toxina Shiga I/química , Triexosilceramidas/química , Acetilgalactosamina/química , Acetilgalactosamina/metabolismo , Acetilglucosamina/química , Acetilglucosamina/metabolismo , Animais , Sítios de Ligação , Células CHO , Sequência de Carboidratos , Cricetulus , Escherichia coli Êntero-Hemorrágica/química , Escherichia coli Êntero-Hemorrágica/patogenicidade , Galactose/química , Galactose/metabolismo , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Expressão Gênica , Globosídeos/biossíntese , Globosídeos/metabolismo , Glucose/química , Glucose/metabolismo , Humanos , Modelos Moleculares , Mutação , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Toxina Shiga I/metabolismo , Toxina Shiga II/química , Toxina Shiga II/metabolismo , Triexosilceramidas/biossíntese
11.
Health Soc Care Community ; 29(5): e97-e106, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33285022

RESUMO

Major transitions in older people's lives can give rise to multifaceted forms of social exclusion, with subsequent impacts for later life health and well-being. With place now a central concept within policy on ageing and community care, there is the potential that it may offer new pathways to support older people undergoing these critical life transitions (CLTs). However, how policy and practice stakeholders working with and on behalf of these population groups understand, conceptualise and capitalise on the involvement of place in CLTs has not been investigated. This paper aims to address this deficit and explores the perspectives of key national and local actors on three CLTs-dementia, bereavement and forced migration-and their relationship with place and exclusion. The analysis involved 18 semi-structured interviews with stakeholders from policy, practice and advocacy spheres related to the CLTs and ageing in general. Interviews highlighted the differences across stakeholders in perceived exclusionary impacts, and the different degrees to which place is conceptualised in relation to these transitions. Findings illustrate the lack of a holistic policy approach to the needs of older people experiencing CLTs that impedes our capacity to truly harness place in supporting older people. The article concludes by arguing for a more nuanced reconstruction of place and its meanings in the context of CLTs.


Assuntos
Envelhecimento , Isolamento Social , Idoso , Humanos , Irlanda , Políticas
12.
Health Place ; 66: 102423, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32916385

RESUMO

The literature recognizes the great diversity of care arrangements among rural-dwelling older people. However, little is known about the complex relationships between spatial, social and infrastructural characteristics of place and the strategies that older people develop to navigate care. Even less is known about how navigating care impacts social exclusion from the perspective of older adults themselves. To fill this gap, in this secondary analysis we draw on data from twenty-one in-depth interviews from two studies conducted in rural environments in Germany and Poland. We identify three main strategies of navigating care in the rural environment: adaptation to circumstances, making use of the environment, and shaping circumstances. We present details from four cases that exemplify how strategies are interconnected with characteristics of place. The relationships between place and navigating care in rural environments is discussed with reference to the overall level of social exclusion experienced by rural-dwelling older adults with continuing care needs.


Assuntos
População Rural , Isolamento Social , Idoso , Alemanha , Humanos , Polônia , Meio Social
13.
Clin Cosmet Investig Dent ; 12: 241-250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636684

RESUMO

PURPOSE: An innovative hybrid toothbrush was designed to function either in manual sonic mode or combined mode (manual and sonic). The primary objective was to assess the efficacy of a new hybrid powered toothbrush (PTB) used in combined mode versus a comparative manual toothbrush (MTB) for plaque removal, after 14 days of twice-daily use under normal conditions. The secondary objectives were to evaluate the gingival state, to evaluate the tolerance of the hybrid PTB and to evaluate its acceptability. MATERIALS AND METHODS: This study was a monocentric, block-randomized, dual treatment, parallel group, and examiner-blinded trial with before and after evaluation. It was conducted on two groups of 55 subjects presenting a visible plaque accumulation (score ≥2 as measured by the Turesky Modification of the Quigley-Hein Plaque Index (TMQHPI)). On Day 1/Day 8/Day 15, the same investigator conducted blind clinical examinations on each subject and evaluated TMQHPI and Papillary Bleeding Score (PBS). On Day 1, the subjects received either the hybrid PTB or the comparative MTB and used it twice daily under normal conditions of use. RESULTS: The hybrid PTB used in its combined mode eliminates dental plaque more efficiently than the comparative MTB, especially in difficult-to-access areas such as posterior and interproximal dental surfaces, while remaining gentle on the gingivae. The PBS was significantly lower with the hybrid toothbrush compared with the reference manual one. CONCLUSION: The new device confirmed previous findings and should improve oral hygiene following the manufacturer's instructions. Moreover, the specific design of the toothbrush means that it can be used according to the oral environment conditions and personal feeling.

14.
Cancers (Basel) ; 12(3)2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156052

RESUMO

Retinol-binding protein 4 (RBP4) is proposed as an adipokine that links obesity and cancer. We analyzed the role of RBP4 in metastasis of breast cancer in patients and in mice bearing metastatic 4T1 and nonmetastatic 67NR mammary gland cancer. We compared the metastatic and angiogenic potential of these cells transduced with Rbp4 (4T1/RBP4 and 67NR/RBP4 cell lines). Higher plasma levels of RBP4 were observed in breast cancer patients with metastatic tumors than in healthy donors and patients with nonmetastatic cancer. Increased levels of RBP4 were observed in plasma, tumor tissue, liver, and abdominal fat. Moreover, the blood vessel network was highly impaired in mice bearing 4T1 as compared to 67NR tumors. RBP4 transductants showed further impairment of blood flow and increased metastatic potential. Exogenous RBP4 increased lung settlement by 67NR and 4T1 cells. In vitro studies showed increased invasive and clonogenic potential of cancer cells treated with or overexpressing RBP4. This effect is not dependent on STAT3 phosphorylation. RBP4 enhances the metastatic potential of breast cancer tumors through a direct effect on cancer cells and through increased endothelial dysfunction and impairment of blood vessels within the tumor.

15.
Health Place ; 60: 102234, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31671377

RESUMO

Understanding the role of place in protecting against social exclusion (SE) and risk during critical life transitions (CLTs) in older age is essential to create effective community-level ageing policies. However, existing knowledge is diffuse across a range of literatures and lacks coherency. Through a two-stage scoping review, this paper aims to synthesise state-of-the-art international research linking place, old-age SE and CLTs. Findings show that: (1) place serves as a setting for, and as a mediator of exclusion resulting from CLTs and (2) theoretical conceptualisation to address the intersection of CLTs, place and SE in later life is underdeveloped. The implications of the state of scientific knowledge on this topic are discussed in relation to future research needs and ageing in place policy.


Assuntos
Meio Social , Isolamento Social , Fatores Etários , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade
16.
Sci Rep ; 9(1): 220, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659229

RESUMO

In this study, novel phosphatidylcholines containing ibuprofen or naproxen moieties were synthesized in good yields and high purities. Under the given synthesis conditions, the attached drug moieties racemized, which resulted in the formation of phospholipid diastereomers. The comperative studies of the cytotoxicity of ibuprofen, naproxen and their phosphatidylcholine derivatives against human promyelocytic leukemia HL-60, human colon carcinoma Caco-2, and porcine epithelial intestinal IPEC-J2 cells were carried out. The results of these studies indicated that phospholipids with NSAIDs at both sn-1 and sn-2 positions (15 and 16) were more toxic than ibuprofen or naproxen themselves, whereas 2-lysophosphatidylcholines (7 and 8) were less toxic against all tested cell lines. Phospholipids with NSAIDs at sn-1 and palmitic acid at sn-2 (9 and 10) were also less toxic against Caco-2 and normal cells (IPEC-J2).


Assuntos
Ibuprofeno/química , Naproxeno/química , Fosfatidilcolinas/síntese química , Fosfatidilcolinas/toxicidade , Animais , Anti-Inflamatórios não Esteroides , Células CACO-2 , Linhagem Celular , Citotoxinas/toxicidade , Células Epiteliais , Humanos , Lisofosfatidilcolinas , Ácido Palmítico , Fosfolipídeos , Suínos
17.
Am J Cancer Res ; 8(11): 2150-2164, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555735

RESUMO

Prolactin-induced protein (PIP) is a small secreted glycoprotein carrying several N-linked carbohydrate chains. The expression of PIP is generally restricted to cells with apocrine properties. It was found in apocrine glands of the axilla, vulva, eyelid, ear canal, and seminal vesicle. Being a secretory protein, PIP is present in seminal plasma, saliva, lacrimal fluid, tears, sweat gland secretion. Little is known about the biological role of PIP. It binds to numerous proteins, however, in most cases the biological role of such interactions is poorly understood. A notable exception is its binding to CD4 receptors present on the surface of T lymphocytes, macrophages, and spermatozoa. The available data suggest that PIP can have immunomodulatory functions and plays an important role in cell-mediate adoptive immunity. PIP binds to bacteria from several genera, which suggests that this glycoprotein may participate also in innate immunity and protection of hosts against microbial infections. Increased levels of PIP were found in several types of human cancer (prostate, sweat and salivary gland cancers). It is especially common in breast cancer, however, data on the expression of PIP in normal and cancerous breast cancer tissues are to some degree conflicting. In early studies, it was shown that PIP is absent or its expression is very low in normal breast epithelium, whereas in breast cancers PIP is frequently expressed and present in large amounts. On the other hand, later study showed that expression of PIP is lower in advanced apocrine carcinomas and invasive carcinomas than in, respectively, in situ carcinomas and adjacent normal tissue. The most recent study revealed that PIP gene expression decreased gradually along with higher stage and grade of breast cancer. In agreement with these data, it was shown that that low levels or the lack of PIP expression are associated with a worse response of breast cancer cells to chemotherapy. It was proposed that PIP plays important role in the development and progression of breast cancer. However, its role in these processes is both unclear and controversial. In this review, the role of PIP in both physiological processes and carcinogenesis is discussed.

18.
Biochem Biophys Res Commun ; 499(2): 260-266, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29567473

RESUMO

Tumour necrosis factor (TNF) is produced by primary human macrophages in response to stimulation by exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) via Toll-like receptor (TLR) signalling. However, uncontrolled TNF production can be deleterious and hence it is tightly controlled at multiple stages. We have previously shown that Bruton's tyrosine kinase (Btk) regulates TLR4-induced TNF production via p38 MAP Kinase by stabilising TNF messenger RNA. Using both gene over-expression and siRNA-mediated knockdown we have examined the role of Btk in TLR7/8 mediated TNF production. Our data shows that Btk acts in the TLR7/8 pathway and mediates Ser-536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human macrophages. These data show an important role for Btk in TLR7/8 mediated TNF production and reveal distinct differences for Btk in TLR4 versus TLR7/8 signalling.


Assuntos
NF-kappa B/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/metabolismo , Transcrição Gênica , Fator de Necrose Tumoral alfa/genética , Regiões 3' não Traduzidas/genética , Tirosina Quinase da Agamaglobulinemia , Pareamento de Bases/genética , Núcleo Celular/metabolismo , Citocinas/biossíntese , Regulação para Baixo/genética , Humanos , Fosforilação , Regiões Promotoras Genéticas/genética , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Drugs Aging ; 34(8): 635-645, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28710707

RESUMO

OBJECTIVE: We studied prescription patterns for non-vitamin K oral anticoagulants (NOACs) in Norway between 2012 and 2015, and compared NOAC and warfarin patient characteristics such as age, gender and cardiovascular (CV) co-medications across reimbursed indications. Factors associated with NOAC prescribing in atrial fibrillation (AF) were also analysed. METHODS: All Norwegian patients (N = 156,124) who received at least one dispensed NOAC or warfarin prescription within the indications of AF, deep vein thrombosis and pulmonary embolism (DVT_PE) or prevention of venous thromboembolic events after a hip or knee surgery (VTE_surg) between 2012 and 2015 were included in the study. Descriptive statistics was applied to compare patient characteristics between NOACs and warfarin across indications and a logistic regression model was used to identify factors associated with NOAC prescribing in AF. RESULTS: NOACs and warfarin were most commonly prescribed in AF (83,729 patients in 2015), followed by DVT_PE (16,077 patients) and lastly in VTE_surg (4060 patients). In 2015, NOACs achieved a dominant (>50%) patient share over warfarin in AF and DVT_PE, and were prescribed in >80% of new oral anticoagulation (OAC) patients. Apixaban, despite its delayed market entry, emerged as the preferred NOAC in VTE_surg (46% share), whereas rivaroxaban captured a 43% patient share in DVT_PE. Warfarin patients were on average older and received more CV co-medication than NOAC patients in AF and DVT_PE. Age, gender and certain CV co-medications emerged as significant predictors of NOAC prescribing in AF. AF patients <70 years old had higher odds of NOAC prescribing (OR 1.19-1.29, depending on age category), in contrast to patients >74 years old (OR 0.51-0.77). Women had 32% higher odds of receiving a NOAC in AF. CONCLUSION: NOACs achieved a dominant market share over warfarin within 3 years from receiving reimbursement in Norway. There were significant differences in patient characteristics between drugs and indications.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Padrões de Prática Médica/tendências , Varfarina/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Tromboembolia/prevenção & controle
20.
Postepy Dermatol Alergol ; 32(1): 21-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25821423

RESUMO

INTRODUCTION: The spreading of bacterial antibiotic resistance among clinical strains of pathogenic bacteria has made investigators to search for other active antibacterial agents which could provide a valuable complement to the existing therapies. AIM: To determine the antibacterial activity of clary sage oil (Salvia sclarea L.) against Staphylococcus clinical strains which were isolated from patients with wound infections. MATERIAL AND METHODS: A comprehensive evaluation of Staphylococcus clinical strain resistance to antibiotics was performed. The constituents of clary sage oil were assayed by GC-FID-MS analysis. The minimal inhibitory concentration (MIC) of the tested essential oil against staphylococci by the micro-dilution broth method was determined. RESULTS: The clary sage oil was active against Staphylococcus aureus, S. epidermidis and S. xylosus with MIC values ranging from 3.75 to 7.00 µl/ml. CONCLUSIONS: The results of the in vitro tests encourage to use formulations containing sage oil as the active natural antimicrobial agent. Because of its antimicrobial properties clary sage oil may be applied to treat wounds and skin infections.

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