Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
J Int Soc Prev Community Dent ; 13(4): 287-298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876584

RESUMO

Aims and Objectives: Periodontitis is a chronic disease affecting the supporting tissues of the teeth and exhibits bidirectional relation with systemic diseases. This study aims to determine the association between chronic periodontitis and erythrocyte functional measures: total red blood cells (RBCs), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC) by systematic review and meta-analysis. Materials and Methods: A systematic search of the electronic databases PUBMED, OVID, Embase, Web on Science, and Google Scholar was undertaken from inception to July 2022. English language studies that evaluated the erythrocyte functional measures in periodontitis and health were selected. Other review reports, letters/opinion articles, studies without a definition of periodontitis, and the concomitant presence of systemic conditions (diabetes, kidney disease, cancer) were excluded. Two reviewers determined full-text eligibility in a blinded process. Meta-Essentials software was used to generate forest plots and to determine heterogeneity and publication bias. Results: Twenty-six studies involving 1082 patients with chronic periodontitis and 980 healthy controls were analyzed. Pooled results showed lower Hb concentration (Hedges' g = -1.16; 95% confidence intervals [CI], -1.7 to -0.62), RBC counts (Hedges' g = -0.85; 95% CI, -1.31 to -0.38) and packed cell volume (-0.56; 95% CI, -1.02 to -0.11) in patients with chronic periodontitis. Conclusion: This meta-analysis showed a decreasing trend in the hematological parameters, including hemoglobin concentration, number of erythrocytes, and hematocrit in patients with chronic periodontitis compared to healthy controls.

2.
PLoS One ; 18(7): e0289335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37523369

RESUMO

Established classifications exist to confirm Sjögren's Disease (SD) (previously referred as Sjögren's Syndrome) and recruit patients for research. However, no established classification exists for diagnosis in clinical settings causing delayed diagnosis. SD patients experience a huge dental disease burden impairing their quality of life. This study established criteria to characterize Indiana University School of Dentistry (IUSD) patients' SD based on symptoms and signs in the electronic health record (EHR) data available through the state-wide Indiana health information exchange (IHIE). Association between SD diagnosis, and comorbidities including other autoimmune conditions, and documentation of SD diagnosis in electronic dental record (EDR) were also determined. The IUSD patients' EDR were linked with their EHR data in the IHIE and queried for SD diagnostic ICD9/10 codes. The resulting cohorts' EHR clinical findings were characterized and classified using diagnostic criteria based on clinical experts' recommendations. Descriptive statistics were performed, and Chi-square tests determined the association between the different SD presentations and comorbidities including other autoimmune conditions. Eighty-three percent of IUSD patients had an EHR of which 377 patients had a SD diagnosis. They were characterized as positive (24%), uncertain (20%) and negative (56%) based on EHR clinical findings. Dry eyes and mouth were reported for 51% and positive Anti-Ro/SSA antibodies and anti-nuclear antibody (ANA) for 17% of this study cohort. One comorbidity was present in 98% and other autoimmune condition/s were present in 53% respectively. Significant differences were observed between the three SD clinical characteristics/classifications and certain medical and autoimmune conditions (p<0.05). Sixty-nine percent of patients' EDR did not mention SD, highlighting the huge gap in reporting SD during dental care. This study of SD patients diagnosed in community practices characterized three different SD clinical presentations, which can be used to generate SD study cohorts for longitudinal studies using EHR data. The results emphasize the heterogenous SD clinical presentations and the need for further research to diagnose SD early in community practice settings where most people seek care.


Assuntos
Síndromes do Olho Seco , Troca de Informação em Saúde , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Qualidade de Vida , Anticorpos Antinucleares
3.
J Clin Med ; 12(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37240704

RESUMO

Emerging data suggest an increasing prevalence of persistent symptoms in individuals affected by coronavirus disease-19 (COVID-19). The objective of this study was to determine the relative frequency of altered taste and smell in COVID reinfection (multiple COVID positive tests) and long COVID (one COVID positive test). We sent an electronic survey to patients in the Indiana University Health COVID registry with positive COVID test results, querying if they were experiencing symptoms consistent with long COVID including altered chemosensory perceptions. Among the 225 respondents, a greater long COVID burden and COVID reinfection was observed in women. Joint pain was reported as the most common symptom experienced by 18% of individuals in the long COVID cohort. In the COVID reinfection cohort >20% of individuals reported headache, joint pain, and cough. Taste perception worse than pre-COVID was reported by 29% and 42% of individuals in the long COVID and COVID reinfection cohorts, respectively. Smell perception worse than pre-COVID was reported by 37% and 46% of individuals in long COVID and COVID reinfection cohorts, respectively. Further, Chi-square test suggested significant association between pre-COVID severity of taste/smell perception and headache in both cohorts. Our findings highlight the prevalence of persistent chemosensory dysfunction for two years and longer in long COVID and COVID reinfection.

4.
JMIR Form Res ; 7: e45281, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37155234

RESUMO

BACKGROUND: Oral ulcers are a common condition affecting a considerable proportion of the population, and they are often associated with trauma and stress. They are very painful, and interfere with eating. As they are usually considered an annoyance, people may turn to social media for potential management options. Facebook is one of the most commonly accessed social media platforms and is the primary source of news information, including health information, for a significant percentage of American adults. Given the increasing importance of social media as a source of health information, potential remedies, and prevention strategies, it is essential to understand the type and quality of information available on Facebook regarding oral ulcers. OBJECTIVE: The goal of our study was to evaluate information on recurrent oral ulcers that can be accessed via the most popular social media network-Facebook. METHODS: We performed a keyword search of Facebook pages on 2 consecutive days in March 2022, using duplicate, newly created accounts, and then anonymized all posts. The collected pages were filtered, using predefined criteria to include only English-language pages wherein oral ulcer information was posted by the general public and to exclude pages created by professional dentists, associated professionals, organizations, and academic researchers. The selected pages were then screened for page origin and Facebook categories. RESULTS: Our initial keyword search yielded 517 pages; interestingly however, only 112 (22%) of pages had information relevant to oral ulcers, and 405 (78%) had irrelevant information, with ulcers being mentioned in relation to other parts of the human body. Excluding professional pages and pages without relevant posts resulted in 30 pages, of which 9 (30%) were categorized as "health/beauty" pages or as "product/service" pages, 3 (10%) were categorized as "medical & health" pages, and 5 (17%) were categorized as "community" pages. Majority of the pages (22/30, 73%) originated from 6 countries; most originated from the United States (7 pages), followed by India (6 pages). There was little information on oral ulcer prevention, long-term treatment, and complications. CONCLUSIONS: Facebook, in oral ulcer information dissemination, appears to be primarily used as an adjunct to business enterprises for marketing or for enhancing access to a product. Consequently, it was unsurprising that there was little information on oral ulcer prevention, long-term treatment, and complications. Although we made efforts to identify and select Facebook pages related to oral ulcers, we did not manually verify the authenticity or accuracy of the pages included in our analysis, potentially limiting the reliability of our findings or resulting in bias toward specific products or services. Although this work forms something of a pilot project, we plan to expand the project to encompass text mining for content analysis and include multiple social media platforms in the future.

5.
ASN Neuro ; 14: 17590914221120190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317290

RESUMO

Inflammation including neuroinflammation is considered a protective response and is directed to repair, regenerate, and restore damaged tissues in the central nervous system. Persistent inflammation due to chronic stress, age related accrual of free radicals, subclinical infections or other factors lead to reduced survival and increased neuronal death. Circadian abnormalities secondary to altered sleep/wake cycles is one of the earliest signs of neurodegenerative diseases. Brain specific or global deficiency of core circadian trans-activator brain and muscle ARNT (Arylhydrocarbon Receptor Nuclear Translocator)-like protein 1 (BMAL1) or that of the transrepressor REV-ERBα, impaired neural function and cognitive performance in rodents. Consistently, transcripts of inflammatory cytokines and host immune responses have been shown to exhibit diurnal variation, in parallel with the disruption of the circadian rhythm. Glucocorticoids that exhibit both a circadian rhythm similar to that of the core clock transactivator BMAL1 and tissue specific ultradian rhythm are critical in the control of neuroinflammation and re-establishment of homeostasis. It is widely accepted that the glucocorticoids suppress nuclear factor-kappa B (NF-κB) mediated transactivation and suppress inflammation. Recent mechanistic elucidations suggest that the core clock components also modulate NF-κB mediated transactivation in the brain and peripheral tissues. In this review we discuss evidence for interactions between the circadian clock components, glucocorticoids and NF-κB signaling responses in the brain and propose glucocorticoid induced leucine zipper (GILZ) encoded by Tsc22d3, as a molecular link that connect all three pathways in the maintenance of CNS homeostasis as well as in the pathogenesis of neuroinflammation-neurodegeneration.


Assuntos
Relógios Circadianos , Ritmo Ultradiano , Humanos , NF-kappa B/metabolismo , Glucocorticoides/farmacologia , Fatores de Transcrição ARNTL/metabolismo , Zíper de Leucina , Doenças Neuroinflamatórias , Inflamação
6.
Front Microbiol ; 12: 727430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707585

RESUMO

Emerging concerns following the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) pandemic are the long-term effects of coronavirus disease (COVID)-19. Dysgeusia in COVID-19 is supported by the abundant expression of the entry receptor, angiotensin-converting enzyme-2 (ACE2), in the oral mucosa. The invading virus perturbs the commensal biofilm and regulates the host responses that permit or suppress viral infection. We correlated the microbial recognition receptors and soluble ACE2 (sACE2) with the SARS-CoV2 measures in the saliva of COVID-19 patients. Data indicate that the toll-like receptor-4, peptidoglycan recognition protein, and sACE2 are elevated in COVID-19 saliva and correlate moderately with the viral load.

8.
Dent J (Basel) ; 9(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068053

RESUMO

As the landscape of oral healthcare and the delivery of services continue to undergo change, the dental hygienist plays an increasing role in assisting dentists with oral diagnosis and preventive strategies. Hence, the dental hygiene curriculum standards require biomedical science instructions, including general and oral pathology. Student learning and cognitive competencies are often measured using multiple-choice questions (MCQs). The objectives of this study were to perform a longitudinal analysis of test items and to evaluate their relation to the absolute grades of the oral pathology course in the dental hygiene curriculum. A total of 1033 MCQs covering different concepts of oral pathology administered from 2015 through 2019 were analyzed for difficulty and discriminatory indices, and the differences between the years were determined by one-way ANOVA. Test reliability as determined by the average KR-20 value was 0.7 or higher for each exam. The mean difficulty index for all exams was 0.73 +/- 0.05, and that of the discriminatory index was 0.33 +/- 0.05. Wide variations were observed in the discriminatory indices of test items with approximately the same difficulty index, as well as in the grade distribution in each cohort. Furthermore, longitudinal data analyses identified low achieving cohorts amongst the groups evaluated for the same knowledge domain, taught with the same instruction, and using similar test tools. This suggest that comparative analyses of tests could offer feedback not only on student learning attributes, but also potentially on the admission processes to the dental hygiene program.

9.
Biomed Pharmacother ; 138: 111405, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33756153

RESUMO

A disproportionate increase in activated nuclear factor-kappa B (NF-κB) has been shown to drive the Aß deposition, neuroinflammation and neurodegeneration in Alzheimer's disease (AD). Hence, selective targeting of activated p65 represents an attractive therapeutic approach for AD. Glucocorticoid induced leucine zipper (GILZ) is a NF-κB interactant that binds and sequesters the activated p65 in the cytoplasm. The p65 binding domain of GILZ adopts a polyproline type II helical conformation, a motif that acts as an adaptable glove in the interface with the binding partner and constitutes an excellent template for drug design. Previously, peptide analogs of the p65 binding domain of GILZ, referred to as GA have been shown to suppress pathology in the lipopolysaccharide induced model of neuroinflammation. In this study, we investigated the CNS delivery of labeled GA administered intraperitoneally in adult mice for a period of upto 24 h. Further, we evaluated the suppressive potential of GA in 5xFAD mice, an aggressive model with five genetic mutations closely associated with human AD. Groups of 5xFAD mice administered GA or control peptide intraperitoneally on alternate days for six weeks were evaluated for Aß deposition, microglia, inflammation and innate immune responses by immunohistochemistry and real time polymerase reaction. GA was observed in proximity with NeuN positive neurons suggesting that the compound crossed the blood brain barrier to reach the brain parenchyma. Further, GA treatment decreased Aß load, reduced Iba1 + microglia and glial fibrillary acidic protein (GFAP)+ astrocytes, inhibited inflammatory cytokines and suppressed toll like receptor (TLR-2, TLR-4) expressions in 5xFAD mice.


Assuntos
Doença de Alzheimer/prevenção & controle , Gliose/prevenção & controle , Imunidade Inata/efeitos dos fármacos , NF-kappa B/farmacologia , Receptores Imunológicos/antagonistas & inibidores , Fatores de Transcrição/farmacologia , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Animais , Feminino , Gliose/genética , Gliose/imunologia , Imunidade Inata/fisiologia , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/imunologia , NF-kappa B/genética , NF-kappa B/uso terapêutico , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Fatores de Transcrição/uso terapêutico , eIF-2 Quinase/genética , eIF-2 Quinase/imunologia
11.
Clin Oral Investig ; 24(7): 2523-2528, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32529494

RESUMO

OBJECTIVE: Soluble toll-like receptor-2 (sTLR2) and soluble CD14 (sCD14) in saliva are defense proteins that bind specific microbe-associated molecular patterns. Since the oral flora changes with aging, the objective of this study is to determine and compare the concentration of sTLR2 and sCD14 in the saliva of healthy individuals in age groups from the first to the sixth decade of life. METHODS: Unstimulated whole saliva was collected after obtaining informed consent. The concentration of sCD14 and sTLR-2 was measured by enzyme-linked immunosorbent assay. Statistical differences between the age groups were determined by analysis of variance. The relationship between the two markers in each age group was evaluated by Pearson's correlation coefficient and linear regression analyses. RESULTS: The concentration of salivary sTLR2 was highest in the youngest, and that of the sCD14 was highest in the oldest age group. While the salivary sCD14 and the sTLR2 exhibited a moderate negative correlation in the youngest, the relationship between the two markers was inversed in the oldest age group. CONCLUSIONS AND CLINICAL RELEVANCE: The results of our exploratory study suggest a need to adjust for age-dependent changes in sCD14 and sTLR2 in healthy saliva while assessing the two proteins as biomarkers.


Assuntos
Envelhecimento , Proteínas e Peptídeos Salivares , Receptor 2 Toll-Like , Adolescente , Adulto , Biomarcadores/análise , Criança , Pré-Escolar , Humanos , Receptores de Lipopolissacarídeos , Pessoa de Meia-Idade , Saliva/metabolismo , Receptor 2 Toll-Like/metabolismo , Adulto Jovem
12.
PLoS One ; 13(12): e0200231, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30571680

RESUMO

Chronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and TLR-4 mRNA exhibited an inverse correlation (r2 = 0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.


Assuntos
Periodontite Crônica/metabolismo , Saliva/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Adulto , Biomarcadores/metabolismo , Periodontite Crônica/diagnóstico , Periodontite Crônica/patologia , Estudos de Coortes , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Domínios Proteicos , RNA Mensageiro/biossíntese , Solubilidade
13.
J Inflamm Res ; 11: 407-419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464573

RESUMO

The transcription factor NF-κB is a critical regulator of immune and inflammatory responses. In mammals, the NF-κB/Rel family comprises five members: p50, p52, p65 (Rel-A), c-Rel, and Rel-B proteins, which form homo- or heterodimers and remain as an inactive complex with the inhibitory molecules called IκB proteins in resting cells. Two distinct NF-κB signaling pathways have been described: 1) the canonical pathway primarily activated by pathogens and inflammatory mediators, and 2) the noncanonical pathway mostly activated by developmental cues. The most abundant form of NF-κB activated by pathologic stimuli via the canonical pathway is the p65:p50 heterodimer. Disproportionate increase in activated p65 and subsequent transactivation of effector molecules is integral to the pathogenesis of many chronic diseases such as the rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and even neurodegenerative pathologies. Hence, the NF-κB p65 signaling pathway has been a pivotal point for intense drug discovery and development. This review begins with an overview of p65-mediated signaling followed by discussion of strategies that directly target NF-κB p65 in the context of chronic inflammation.

14.
Alzheimers Dement (N Y) ; 4: 488-498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30338290

RESUMO

INTRODUCTION: Glucocorticoid-induced leucine zipper is a regulatory protein that sequesters activated nuclear factor-kappa B p65. Previously, we showed that rationally designed analogs of the p65-binding domain of glucocorticoid-induced leucine zipper, referred to as glucocorticoid-induced leucine zipper analogs (GAs), inhibited amyloid ß-induced metabolic activity and inflammatory cytokines in mixed brain cell cultures. Here, we investigate the therapeutic efficacy of GA in an Alzheimer's disease model. METHODS: GA and control peptides were synthesized covalently as peptide amides with the cell-penetrating agent. C57Bl/6J mice induced with lipopolysaccharide-mediated neuroinflammation (250 mg/kg i.p/day for six days) were treated on alternate days with GA-1, GA-2, or control peptides (25 mg/kg i.v). Brain tissues were assessed for gliosis, cytokines, and antiapoptotic factors. RESULTS: The brain tissues of GA-1- and GA-2-treated mice exhibited significantly reduced gliosis, suppressed inflammatory cytokines, and elevated antiapoptotic factors. DISCUSSION: The antineuroinflammatory effects of GA suggest potential therapeutic application for Alzheimer's disease.

15.
Biochem Res Int ; 2018: 7463796, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487749

RESUMO

Type 2 diabetes mellitus (T2DM) is emerging as a metabolic epidemic worldwide. Pathologically, dysregulation of many biological pathways precedes hyperglycemia and the clinical diagnosis of T2DM. Changing trajectories along the process of T2DM development necessitates frequent measurement of biomarkers for early identification of at-risk individuals and successful prevention. Increase in circulating inflammatory adipokines has been suggested as predictive of T2DM. Human saliva is an easily accessible biospecimen amenable for painless frequent collection and possesses nearly 50% of serum proteome. In this study, we measured the adipokines resistin, visfatin, TNF-α, and ghrelin as markers for T2DM in unstimulated whole saliva (UWS) using specific assay kits. Resistin and visfatin concentrations were significantly higher in T2DM saliva. Although the concentration of acylated or unacylated ghrelin was lower in diabetic saliva, the decrease was not significant. Since resistin and visfatin are biomarkers integral to T2DM pathology, their salivary assessments may receive clinical acceptance.

16.
Front Aging Neurosci ; 10: 432, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30740047

RESUMO

Glucocorticoids (GCs) are steroid hormones secreted as the end-product of the neuroendocrine stress cascade. Both absence and elevated GC mediate neurotoxic responses, suggesting that a narrow window ranging from physiological to slightly high GC mediate protective responses. The beneficial effects of GC are attributed to the transactivation of regulatory proteins and inhibition mediated by glucocorticoid receptor (GR) interactions with other co-factors. The glucocorticoid induced leucine zipper (GILZ) is a gene strongly upregulated by GC and mediates many of the anti-inflammatory and anti-proliferative effects of GC. Although GILZ is constitutively expressed in many tissues including the brain, the expression has been shown to occur with varying dynamics suggesting that the local milieu modulates its expression with consequent effects on cellular responses. Here we investigated the expression profile of GILZ in lipopolysaccharide (LPS) mediated neuroinflammation model of Alzheimer's disease (AD). Our data suggest that the GILZ expression is downregulated in neuroinflammation correlating inversely with the pro-inflammatory cytokines and innate immune responses.

17.
Mol Neurobiol ; 54(10): 8063-8070, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27889894

RESUMO

The central nervous system (CNS) is a large network of intercommunicating cells that function to maintain tissue health and homeostasis. Considerable evidence suggests that glucocorticoids exert both neuroprotective and neurodegenerative effects on the CNS. Glucocorticoids act by binding two related receptors in the cytoplasm, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The glucocorticoid receptor complex mediates cellular responses by transactivating target genes and by protein: protein interactions. The paradoxical effects of glucocorticoids on neuronal survival and death have been attributed to the concentration and the ratio of mineralocorticoid to glucocorticoid receptor activation. Glucocorticoid-induced leucine zipper (GILZ) is a recently identified protein transcriptionally upregulated by glucocorticoids. Constitutively, expressed in many tissues including brain, GILZ mediates many of the actions of glucocorticoids. It mimics the anti-inflammatory and anti-proliferative effects of glucocorticoids but exerts differential effects on stem cell differentiation and lineage development. Recent experimental data on the effects of GILZ following induced stress or trauma suggest potential roles in CNS diseases. Here, we provide a short overview of the role of GILZ in CNS health and discuss three potential rationales for the role of GILZ in Alzheimer's disease pathogenesis.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Glucocorticoides/farmacologia , Zíper de Leucina/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Sistema Nervoso Central/metabolismo , Humanos , Receptores de Glucocorticoides/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
PLoS One ; 11(10): e0160314, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27764084

RESUMO

In the central nervous system (CNS), activation of the transcription factor nuclear factor-kappa B (NF-κß) is associated with both neuronal survival and increased vulnerability to apoptosis. The mechanisms underlying these dichotomous effects are attributed to the composition of NF-κΒ dimers. In Alzheimer's disease (AD), ß-amyloid (Aß) and other aggregates upregulate activation of p65:p50 dimers in CNS cells and enhance transactivation of pathological mediators that cause neuroinflammation and neurodegeneration. Hence selective targeting of activated p65 is an attractive therapeutic strategy for AD. Here we report the design, structural and functional characterization of peptide analogs of a p65 interacting protein, the glucocorticoid induced leucine zipper (GILZ). By virtue of binding the transactivation domain of p65 exposed after release from the inhibitory IκΒ proteins in activated cells, the GILZ analogs can act as highly selective inhibitors of activated p65 with minimal potential for off-target effects.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Apoptose/efeitos dos fármacos , Neurônios/metabolismo , Peptídeos/farmacologia , Fator de Transcrição RelA/metabolismo , Sítios de Ligação , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Células Cultivadas , Feto/citologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Simulação de Acoplamento Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Peptídeos/química , Peptídeos/genética , Peptídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Dent Res J (Isfahan) ; 13(3): 199-205, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27274338

RESUMO

BACKGROUND: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. MATERIALS AND METHODS: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. RESULTS: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. CONCLUSION: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated.

20.
Biomark Insights ; 10: 39-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26005324

RESUMO

The alarming increase in type 2 diabetes mellitus (T2DM) underscores the need for efficient screening and preventive strategies. Select protein biomarker profiles emerge over time during T2DM development. Periodic evaluation of these markers will increase the predictive ability of diabetes risk scores. Noninvasive methods for frequent measurements of biomarkers are increasingly being investigated. Application of salivary diagnostics has gained importance with the establishment of significant similarities between the salivary and serum proteomes. The objective of this study is to identify T2DM-specific salivary biomarkers by literature-based discovery. A serial interrogation of the PubMed database was performed using MeSH terms of specific T2DM pathological processes in primary and secondary iterations to compile cohorts of T2DM-specific serum markers. Subsequent search consisted of mining for the identified serum markers in human saliva. More than 60% of T2DM-associated serum proteins have been measured in saliva. Nearly half of these proteins have been reported in diabetic saliva. Measurements of salivary lipids and oxidative stress markers that can exhibit correlated saliva plasma ratio could constitute reliable factors for T2DM risk assessment. We conclude that a high percentage of T2DM-associated serum proteins can be measured in saliva, which offers an attractive and economical strategy for T2DM screening.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...