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2.
J Indian Prosthodont Soc ; 23(4): 347-355, 2023.
Article in English | MEDLINE | ID: mdl-37861611

ABSTRACT

Aim: Neglected oral health is a major issue, especially in women of developing countries, leading to early loss of teeth which may further lead to malnutrition, degradation of overall health, and increased chances of osteoporosis. Thus, the aim of this study was to assess the effect of food supplement on masticatory performance, nutritional status, electromyography (EMG) (masseter and temporalis), and bone mineral density (BMD) among women rehabilitated with complete denture. Settings and Design: Hospital based randomized controlled trial. Materials and Methods: A randomized controlled trial with 106 women of 45-65 years rehabilitated with complete denture (56 received food supplement and 50 did not receive food supplement) and 52 healthy control was conducted. The outcomes were assessed at baseline and 3 and 6 months of follow up (after complete denture fabrication). Outcomes were measured via masticatory performance, nutritional status (hemoglobin, serum calcium, albumin, and Vitamin D level), EMG of masseter and temporalis muscles, and BMD. Statistical Analysis Used: Friedman's analysis of variance test was used as a nonparametric test, and the Statistical Package for the Social Sciences version 21.0 at a significance level of 0.05 was used for statistical analysis. Results: A statistically significant change was observed during follow up for the group with food supplement for BMD, EMG, and masticatory performance. When biochemical parameters were assessed during follow up, no statistically significant change was observed for both groups (with and without food supplement), except for serum calcium level in group which received food supplement. Conclusion: It was found that the magnitude of effect was remarkably meager in food supplement group which could be perhaps due to less time given for follow up period. Longer duration of trials would yield better results.


Subject(s)
Calcium , Mouth, Edentulous , Female , Humans , Dietary Supplements , Denture, Complete , Nutritional Status
3.
J Oral Biol Craniofac Res ; 13(5): 584-588, 2023.
Article in English | MEDLINE | ID: mdl-37576799

ABSTRACT

Aim: To know attitudes, perceptions and barriers towards the use of Artificial Intelligence (AI) in dentistry in India among undergraduate and postgraduate students. Methodology: A questionnaire-based cross-sectional study was conducted among participants pursuing graduation and postgraduation. The questionnaire consisted of 23 close-ended and 2 open-ended questions divided into various sections of attitude, perception and barriers. The data was analysed using Statistical Package for Social Sciences (SPSS) version 24.0. Result: Out of 937 responses, 55.2% responded that they get information about AI from social media platforms. 51.3% of respondents have basic knowledge about the use of AI in dentistry. 59.6% agreed that AI can be used as a "definitive diagnostic tool" in the diagnosis of diseases. 66.5% agreed that AI can be used for radiographic diagnosis of tooth caries. 71.3% stated that AI can be used as a "treatment planning tool" in dentistry. 55.7% stated that AI should be part of undergraduate dental training. Conclusion: This study concluded that both dental students are aware of the concept of AI. Participants were positive when asked if AI can increase the efficiency of diagnosis, prognosis and treatment planning procedures as well as in managing patient data. Both participants believed that the barriers to the introduction of AI in dentistry are a lack of technical resources and a lack of training personnel in college.

4.
J Indian Prosthodont Soc ; 22(4): 314-327, 2022.
Article in English | MEDLINE | ID: mdl-36511065

ABSTRACT

The study aimed to assess the effect of mandibular advancement device (MAD) in patients with obstructive sleep apnea for reduction in 24-h mean blood pressure, sleep quality, Apnea Hypopnea Index (AHI), and patient compliance, compared to continuous positive airway pressure (CPAP), other interventions, or no treatment. Three different databases such as PubMed, EMBASE, and CENTRAL were searched using different search terms till July 2021 as per the inclusion and exclusion criteria. After inclusion of studies, data extraction including risk of bias assessment was done. For each study, we used odds ratio, mean difference, and 95% confidence interval to assess and synthesize the outcomes. The quality of evidence was evaluated as per the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Twenty-one randomized controlled trials were included: 497 patients in the MAD group, 239 patients in the CPAP group, and 274 patients in the sham group. In MAD-CPAP comparison, the results favored CPAP in the reduction of AHI of 3.48 (1.76-5.19). However, unclear results were found for sleep quality measured as Epworth Sleepiness Scale (ESS), patient compliance, and 24-h mean blood pressure. In MAD-sham comparison, the results favored MAD in the reduction of AHI of - 8.39 (-10.90--5.88] and ESS of - 0.91 (-1.70--0.12) and favored sham in terms of patient compliance while, unclear results for 24-h mean blood pressure. The GRADE score indicated that the quality of evidence is very low, low, and moderate for different outcomes. CPAP in comparison to MAD and MAD in comparison to sham showed a significant AHI reduction. However, patient compliance and 24-h mean blood pressure were not significantly different in MAD-CPAP or MAD-sham. Quality of evidence is very low and low when MAD was compared with CPAP and sham, respectively, for AHI.


Subject(s)
Mandibular Advancement , Sleep Apnea, Obstructive , Humans , Mandibular Advancement/methods , Sleep Apnea, Obstructive/therapy , Continuous Positive Airway Pressure/methods , Patient Compliance , Occlusal Splints
5.
J Food Sci Technol ; 59(8): 3283-3295, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35872732

ABSTRACT

Dahi is widely used fermented milk product in India. Low Density Polyethylene (LDPE) is the most extensively used packaging material for Dahi in India. The present study was conducted to develop the analytical methods for extraction and migration of chemical additives from LDPE into dahi. Characterization of dahi packaging materials collected from five different firms was done by Fourier Transform Infrared Spectroscopy. Focused ultrasound solid liquid extraction method was observed to be better as compared to solid liquid extraction method as the former extracted maximum additives from the LDPE. Out of total 76 chemical additives extracted from LDPE, only eight (10.52%) matched with the existing positive list of polyolefins prescribed by Bureau of Indian Standads (BIS). The overall migration of chemical additives from all the LDPE samples was below their maximum limit as given by BIS standards. Chemical additives which migrated into the simulants included the antioxidants, fatty acids and their derivatives, unreacted hydrocarbons, plasticizers, lubricants and surfactant etc.

6.
Environ Sci Pollut Res Int ; 28(42): 58819-58836, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33410029

ABSTRACT

Hydrocarbon is a primary source of energy in the current urbanized society. Considering the increasing demand, worldwide oil productions are declining due to maturity of oil fields and because of difficulty in discovering new oil fields to substitute the exploited ones. To meet current and future energy demands, further exploitation of oil resources is highly required. Microorganisms inhabiting in these areas exhibit highly diverse catabolic activities to degrade, transform, or accumulate various hydrocarbons. Enrichment of hydrocarbon-utilizing bacteria in oil basin is caused by continuous long duration and low molecular weight hydrocarbon microseepage which plays a very important role as an indicator for petroleum prospecting. The important microbial metabolic processes in most of the oil reservoir are sulfate reduction, fermentation, acetogenesis, methanogenesis, NO3- reduction, and Fe (III) and Mn (IV) reduction. The microorganisms residing in these sites have critical control on petroleum composition, recovery, and production methods. Physical characteristics of heavy oil are altered by microbial biotransformation and biosurfactant production. Considering oil to be one of the most vital energy resources, it is important to have a comprehensive understanding of petroleum microbiology. This manuscript reviews the recent research work referring to the diversity of bacteria in oil field and reservoir sites and their applications for enhancing oil transformation in the target reservoir and geomicrobial prospecting scope for petroleum exploration.


Subject(s)
Archaea , Petroleum , Bacteria , Biodegradation, Environmental , Bioprospecting , Hydrocarbons , Oil and Gas Fields
7.
Natl J Maxillofac Surg ; 11(1): 94-97, 2020.
Article in English | MEDLINE | ID: mdl-33041584

ABSTRACT

OBJECTIVES: A randomized prospective double-blind study was conducted to determine the efficacy of sub-mucosal local infiltration vs. intravenous dexamethasone in reducing postoperative pain, swelling and trismus after surgical removal of impacted mandibular third molars. MATERIALS AND METHODS: Forty five patients were included in the study and were randomly divided into three groups. Each group consisted of 15 patients for which the first and second groups were given 8 mg of dexamethasone intrlesionally & intravenously respectively, at 30 minutes prior to surgery; the third group served as control. Duration of facial swelling was evaluated subjectively by the patients themselves. Severity of postoperative pain was quantified by counting the number of analgesics taken by the patients during and after surgery (six subsequent days). Postoperative trismus was determined by measuring the maximum incisal opening before surgery and on the seventh day. RESULTS: Results showed that duration of postoperative edema was almost the same in the three test groups. During surgery, the intravenous dexamethasone group showed a significantly lesser pain than the other two groups; the intralesional dexamethasone group showed less marked pain than the control group. Additionally, patients who had taken steroids had a marked increase in the incisal opening postoperatively over the control group. Trismus was significantly reduced in the methylprednisolone group as compared to the dexamethasone group. CONCLUSION: It is concluded that both preoperative local infiltration and intravenous administration of dexamethasone significantly reduced postoperative pain and trismus after surgical removal of mandibular third molars. An intravenous dexamethasone is more effective in reducing postoperative inflammatory sequelae than its intralesional route.

8.
J Oral Biol Craniofac Res ; 7(3): 188-192, 2017.
Article in English | MEDLINE | ID: mdl-29123998

ABSTRACT

OBJECTIVES: The present evaluate the feasibility of Computed tomography (Dentascan), in assessment of the implant site in posterior maxilla & mandible. MATERIAL AND METHODS: data of total 11 patients with 20 implant sites were involved in the present study. Out of the 20 implant sites selected 10 were in posterior maxilla and 10 in posterior mandible. All the patients were routinely examined by panoramic radiography and CT. All images obtained i.e., conventional panoramic radiograph, and film based Dentascan MPR- CT images were evaluated for the detectability of mandibular canal at the mental foramen, 1 cm, 2 cm, and 3 cm posterior to mental foramen. The judgments were then compared by using the four point grading score. RESULTS: Both the statistical analysis and radiographic observation showed that Dentascan MPR CT gives significantly clearer images at the mental foramen and 1 cm, 2 cm , 3 cm posterior to it. Dentascan also provides significantly better visualization of the vital structures along with the bone density. The panoramic and Dentascan MPR CT images did not show a significant difference in visualization of the crest of alveolar ridge in both maxillary as well as the mandibular arch. CONCLUSION: The Dentascan MPR- CT images revealed significantly clearer images as well as better visualization of the vital structures than conventional panoramic radiography. Apart from providing clearer images Dentascan also gives the buccopalatal/buccolingual dimension at the implant site, along with the density of the available bone.

9.
J Oral Biol Craniofac Res ; 7(2): 123-126, 2017.
Article in English | MEDLINE | ID: mdl-28706787

ABSTRACT

INTRODUCTION: Host response and environmental factors are known to modify periodontal status adversely. Presently serum, saliva, and GCF are being investigated for its biochemical constituents. GCF contains array of biochemical factors, offering potential use as a diagnostic or prognostic biomarker of the biologic state of the periodontium in health and disease. Alkaline phosphatase is produced locally in the periodontium and shows positive correlation with disease activity and PD. Present study was designed to analyze the levels of ALP in GCF and serum of patients with gingivitis, chronic & aggressive periodontitis before and after SRP & to compare the difference within the study groups. METHODS: OPD patients grouped into: Gingivitis, Aggressive periodontitis & chronic periodontitis patients. Clinical parameters recorded for each patient prior to therapy. Pooled GCF samples collected using micro capillary tubes from the deepest pocket sites for each patient and stored at -70° C. Serum samples also collected and stored at -20° C. Each patient was subjected to scaling and root planing with two weeks maintenance recall. After 6 to 8 weeks GCF and serum samples collected again and all clinical parameters rerecorded. GCF and serum samples analyzed for levels of ALP by using para nitro phenol assay for the three groups. RESULTS: ALP levels in GCF increased significantly during active phase of disease followed by statistically significant reduction after phase I therapy. Baseline levels of ALP in GCF was CP > AP > G with maximum reduction in GCF ALP after SRP in G > CP > AP group.

10.
Natl J Maxillofac Surg ; 8(2): 106-109, 2017.
Article in English | MEDLINE | ID: mdl-29386812

ABSTRACT

AIM: Present study is designed to explore the effect of sodium bicarbonate oral rinse on salivary pH and oral micro flora. MATERIALS AND METHODS: Twenty five healthy subjects were recruited for the study in department of dentistry in Era Medical College. Subjects were abstained from tooth brushing overnight pre rinse (control) samples were collected after one hour of dinner and were asked to rinse with pre calibrated freshly prepared sodium bicarbonate solution. The salivary samples were then collected the following morning using sterile gauze in marked bottles. Aerobic bacterial culture was done by plating the sample directly from the swab on the surface of Blood agar and Mac Conkeys media respectively. The colony forming units and ph were calculated for the pre rinse and post rinse saliva sample. RESULT: Results shows that salivary pH increased significantly after sodium Bicarbonate oral rinse. There was a marginal decrease in number of CFU/ml for bacteria especially Viridans Streptococci, Moraxella species. CONCLUSION: Sodium Bicarbonate oral rinse may be considered as a cheap and effective alternative for chlorhexidine and alcohol based mouth wash, especially where long duration usage is required.

11.
J Cell Physiol ; 2015 May 07.
Article in English | MEDLINE | ID: mdl-25953328

ABSTRACT

The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression. Protein kinase C (PKC) is often found to regulate the action of nuclear receptors and cross talk between this kinase family and JNK and/or PI3K has been shown in several settings. We have therefore investigated a potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found to attenuate the induction of ABCA1 protein expression, the activation of the JNK signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed further by the use of more isotype-specific inhibitors. These studies therefore reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA in human macrophages. This article is protected by copyright. All rights reserved.

12.
J Cell Biochem ; 116(9): 2032-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25752819

ABSTRACT

The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression. Protein kinase C (PKC) is often found to regulate the action of nuclear receptors and cross talk between this kinase family and JNK and/or PI3K has been shown in several settings. We have, therefore, investigated a potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found to attenuate the induction of ABCA1 protein expression, the activation of the JNK signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed further by the use of more isotype-specific inhibitors. These studies, therefore, reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA in human macrophages.


Subject(s)
ATP Binding Cassette Transporter 1/metabolism , Hydroxycholesterols/pharmacology , Macrophages/drug effects , Protein Kinase C/metabolism , Tretinoin/pharmacology , ATP Binding Cassette Transporter 1/antagonists & inhibitors , Alitretinoin , Cell Line , Gene Expression Regulation/drug effects , Humans , Indoles/pharmacology , Liver X Receptors , MAP Kinase Signaling System/drug effects , Macrophages/cytology , Maleimides/pharmacology , Orphan Nuclear Receptors/agonists , Orphan Nuclear Receptors/metabolism , Retinoid X Receptors/agonists , Retinoid X Receptors/metabolism
13.
J Contemp Dent Pract ; 15(1): 34-6, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-24939262

ABSTRACT

The purpose of this study is to analyze the incidence of complications in a group of 171 patients in whom extractions of impacted mandibular third molar have been performed by two oral surgeons between the period April 2010 and March 2012. This retrospective study comprises evaluation of 270 impacted mandibular third molars which were classified into two groups A and B on the basis of procedure of osteotomy only and osteotomy and odontotomy both respectively. Total no of complications reported were 40 (14.81%). Maximum no of cases reported alveolar osteitis (AO) (11.11%) while other complications reported root tip fractures (2.22%), lingual nerve parasthesia and TMJ problems (each 0.74%) in descending frequency. Conclusion drawn is that the risk of complications in extractions of impacted mandibular third molars always exists, and extractions associated with both osteotomy and odontotomy are associated with higher risk of complications.


Subject(s)
Molar, Third/surgery , Postoperative Complications , Tooth Extraction/adverse effects , Dry Socket/etiology , Female , Follow-Up Studies , Humans , Lingual Nerve Injuries/etiology , Male , Mandible/surgery , Operative Time , Osteotomy/methods , Pain, Postoperative/etiology , Paresthesia/etiology , Retrospective Studies , Temporomandibular Joint Disorders/etiology , Tooth Fractures/etiology , Tooth Root/injuries
14.
J Conserv Dent ; 17(2): 159-63, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24778514

ABSTRACT

AIM: The aim of the following study is to compare the evaluation of different irrigation activation system-F-File, CanalBrush (CB) and EndoActivator (EA) in removing smear layer from root canal. MATERIALS AND METHODS: Root canals of eighty single rooted decoronated premolar teeth were instrumented using crown-down technique and then equally divided into four groups on basis of irrigation activation methods used: Without irrigation - control group, irrigation with F-File, CB, EA into Group I, II, III respectively. Samples were then longitudinally sectioned and examined under scanning electron microscope by three qualified observers using score from 1 to 4. Data was analyzed using Statistical Package for Social Sciences (SPSS), version 15.0 (SPSS Inc., Chicago IL) at significance level of P ≤ 0.05. RESULTS: Minimum mean score was observed in Group II at coronal, apical locations. Group III had minimum score at middle third. Groups difference in score were found to be significant statistically for all three locations as well as for overall assessment (P < 0.001). CONCLUSION: CB remove smear layer more efficiently from the root canal than F-File and EA in coronal and apical region.

15.
J Virol ; 85(13): 6725-35, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21507983

ABSTRACT

The activation of AP-1 is a hallmark of cell transformation by tyrosine kinases. In this study, we characterize the role of AP-1 proteins in the transformation of chicken embryo fibroblasts (CEF) by v-Src. In normal CEF, the expression of a dominant negative mutant of c-Jun (TAM67) induced senescence. In contrast, three distinct phenotypes were observed when TAM67 was expressed in v-Src-transformed CEF. While senescent cells were also present, the inhibition of AP-1 caused apoptosis in a fraction of the v-Src-transformed cells. In addition, cells containing lipid-rich vesicles accumulated, suggesting that a subpopulation of the v-Src-transformed cells underwent differentiation in response to the inhibition of AP-1. JunD and Fra-2 were the main components of this factor, while c-Jun accounted for a minor fraction of AP-1 in v-Src-transformed CEF. The downregulation of c-Jun expression by short hairpin RNA (shRNA) induced senescence in normal and v-Src-transformed cells. In contrast, a high incidence of apoptosis was caused by the downregulation of JunD, suggesting that it is required for the survival of v-Src-transformed CEF. Levels of the p53 tumor suppressor were elevated under conditions of JunD inhibition. Repression of p53 by shRNA enhanced the survival and anchorage-independent proliferation of v-Src-transformed CEF with JunD/AP-1 inhibition. The inhibition of Fra-2 had no visible phenotype in normal CEF but caused the appearance of lipid-rich vesicles in v-Src-transformed CEF. Therefore, AP-1 facilitated transformation by acting as a survival factor, by inhibiting premature entry into senescence, and by blocking the differentiation of v-Src-transformed CEF.


Subject(s)
Cell Transformation, Viral , Fibroblasts/virology , Gene Expression Regulation , Genes, src , Genetic Pleiotropy/physiology , Rous sarcoma virus/physiology , Transcription Factor AP-1/metabolism , Animals , Cell Line, Transformed , Chick Embryo , Enzyme Activation , Fibroblasts/metabolism , Fibroblasts/physiology , Fos-Related Antigen-2 , Genetic Pleiotropy/genetics , Proto-Oncogene Proteins c-jun/genetics , Proto-Oncogene Proteins c-jun/metabolism , Transcription Factor AP-1/genetics
16.
Int J Biochem Cell Biol ; 43(5): 805-11, 2011 May.
Article in English | MEDLINE | ID: mdl-21334453

ABSTRACT

Atherosclerosis is an inflammatory disorder of the vasculature that is orchestrated by the action of cytokines. Macrophages play a prominent role in all stages of this disease, including foam cell formation, production of reactive oxygen species, modulation of the inflammatory response and the regulation of the stability of atherosclerotic plaques. The role of the matrix metalloproteinase family in the control of plaque stability is well established. A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS) family has been implicated in several diseases and the expression of ADAMTS-4 in macrophages of atherosclerotic lesions has suggested a potential role for this protease in atherosclerosis. However, the action of cytokines on the expression of ADAMTS-4 in macrophages is poorly understood. We have investigated here the effect of transforming growth factor-ß (TGF-ß) on ADAMTS-4 expression in macrophages along with the regulatory mechanisms underlying its actions. Consistent with the anti-atherogenic role of TGF-ß, this cytokine decreased the expression of ADAMTS-4 mRNA and protein in human macrophages. Transient transfection assays showed that the -100 to +10 promoter region contained the minimal TGF-ß response elements. Small-interfering RNA-mediated knockdown revealed a critical role for Smads, p38 mitogen-activated protein kinase and c-Jun in the action of TGF-ß on ADAMTS-4 mRNA expression. These studies show for the first time that TGF-ß inhibits the expression of ADAMTS-4 in human macrophages and identifies the signalling pathways underlying this response. The inhibition of macrophage ADAMTS-4 expression is likely to contribute to the anti-atherogenic, plaque stabilisation action of TGF-ß.


Subject(s)
ADAM Proteins/metabolism , Gene Expression Regulation, Enzymologic/drug effects , JNK Mitogen-Activated Protein Kinases/metabolism , Macrophages/drug effects , Procollagen N-Endopeptidase/metabolism , Smad Proteins/metabolism , Transforming Growth Factor beta1/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , ADAM Proteins/genetics , ADAMTS4 Protein , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Cell Line, Tumor , Down-Regulation/drug effects , Humans , Macrophages/metabolism , Procollagen N-Endopeptidase/genetics , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transforming Growth Factor beta1/therapeutic use
17.
Cell Signal ; 23(3): 542-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21070853

ABSTRACT

Liver X receptors (LXRs) are ligand-dependent transcription factors that are activated by metabolites of cholesterol, oxysterols, and a number of synthetic agonists. LXRs play potent anti-atherogenic roles in part by stimulating the efflux of cholesterol from macrophage foam cells. The LXR-induced expression of ATP-binding cassette transporter (ABC)-A1 and Apolipoprotein E (ApoE) in macrophages is essential for the stimulation of cholesterol efflux and the prevention of atherosclerotic development. Unfortunately, the signaling pathways underlying such regulation are poorly understood and were therefore investigated in human macrophages. The expression of ApoE and ABCA1 induced by synthetic or natural LXR ligands [TO901317, GW3965, and 22-(R)-hydroxycholesterol (22-(R)-HC), respectively] was attenuated by inhibitors of c-Jun N-terminal kinase (JNK) (curcumin and SP600125) and phosphoinositide 3-kinase (PI3K) (LY294002). Similar results were obtained with ABCG1 and LXR-α, two other LXR target genes. LXR agonists activated several components of the JNK pathway (SEK1, JNK and c-Jun) along with AKT, a downstream target for PI3K. In addition, dominant negative mutants of JNK and PI3K pathways inhibited the LXR-agonists-induced activity of the ABCA1 and LXR-α gene promoters in transfected cells. LXR agonists also induced the binding of activator protein-1 (AP-1), a key transcription factor family regulated by JNK, to recognition sequences present in the regulatory regions of the ApoE and ABCA1 genes. These studies reveal a novel role for JNK and PI3K/AKT signaling in the LXR-regulated expression in macrophages of several key genes implicated in atherosclerosis.


Subject(s)
JNK Mitogen-Activated Protein Kinases/physiology , Macrophages/enzymology , Orphan Nuclear Receptors/metabolism , Phosphatidylinositol 3-Kinases/physiology , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/biosynthesis , ATP-Binding Cassette Transporters/genetics , Cells, Cultured , Cholesterol/metabolism , Humans , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Liver X Receptors , Macrophages/drug effects , Orphan Nuclear Receptors/agonists , Orphan Nuclear Receptors/genetics , Phosphoinositide-3 Kinase Inhibitors , Signal Transduction , Transcription Factor AP-1/metabolism , Transcriptional Activation
18.
J Immunol ; 184(10): 5827-34, 2010 May 15.
Article in English | MEDLINE | ID: mdl-20410491

ABSTRACT

TNF-like protein 1A (TL1A), a TNF superfamily cytokine that binds to death receptor 3 (DR3), is highly expressed in macrophage foam cell-rich regions of atherosclerotic plaques, although its role in foam cell formation has yet to be elucidated. We investigated whether TL1A can directly stimulate macrophage foam cell formation in both THP-1 and primary human monocyte-derived macrophages with the underlying mechanisms involved. We demonstrated that TL1A promotes foam cell formation in human macrophages in vitro by increasing both acetylated and oxidized low-density lipoprotein uptake, by enhancing intracellular total and esterified cholesterol levels and reducing cholesterol efflux. This imbalance in cholesterol homeostasis is orchestrated by TL1A-mediated changes in the mRNA and protein expression of several genes implicated in the uptake and efflux of cholesterol, such as scavenger receptor A and ATP-binding cassette transporter A1. Furthermore, through the use of virally delivered DR3 short-hairpin RNA and bone marrow-derived macrophages from DR3 knockout mice, we demonstrate that DR3 can regulate foam cell formation and contributes significantly to the action of TL1A in this process in vitro. We show, for the first time, a novel proatherogenic role for both TL1A and DR3 that implicates this pathway as a target for the therapeutic intervention of atherosclerosis.


Subject(s)
Cell Differentiation/immunology , Foam Cells/cytology , Foam Cells/immunology , Receptors, Tumor Necrosis Factor, Member 25/physiology , Signal Transduction/immunology , Tumor Necrosis Factor Ligand Superfamily Member 15/physiology , Animals , Atherosclerosis/immunology , Atherosclerosis/pathology , Biological Transport/immunology , Cell Line, Tumor , Cells, Cultured , Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Cholesterol Ester Transfer Proteins/metabolism , Female , Foam Cells/pathology , Humans , Intracellular Fluid/immunology , Intracellular Fluid/metabolism , Lipoproteins, LDL/metabolism , Mice , Mice, Knockout , Receptors, Tumor Necrosis Factor, Member 25/deficiency , Up-Regulation/immunology
19.
Int J Biochem Cell Biol ; 42(1): 113-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19800021

ABSTRACT

Elevated circulating levels of acute phase proteins (APP) are associated with inflammation and inflammatory disorders such as cardiovascular disease. APP are mainly synthesised by hepatocytes and their transcription is induced by pro-inflammatory cytokines such as interleukin-1 (IL-1). The molecular mechanisms underlying the IL-1-induced expression of key transcription factors implicated in the regulation of APP are poorly understood. We have investigated this aspect using the CCAAT/enhancer binding protein-delta (C/EBPdelta) as a model gene. IL-1 induced the expression of C/EBPdelta mRNA and protein in the human hepatoma Hep3B cell line, a widely employed model system for studies on cytokine signalling in relation to the expression of APP. The IL-1-mediated induction of C/EBPdelta expression was attenuated in the presence of pharmacological inhibitors against c-Jun N-terminal kinase (JNK) (curcumin and SP600125), casein kinase 2 (CK2) (apigenin) and nuclear factor-kappaB (NF-kappaB) (NF-kappaB activation inhibitor). RNA interference assays showed significant attenuation of the IL-1-induced expression of C/EBPdelta following knockdown of the p50 and p65 subunits of NF-kappaB. IL-1 induced NF-kappaB DNA binding and activation by this transcription factor and this was attenuated by curcumin and apigenin. Taken together, these results suggest a potentially crucial role for NF-kappaB in the IL-1-induced expression of C/EBPdelta, and thereby downstream APP genes regulated by this transcription factor.


Subject(s)
CCAAT-Enhancer-Binding Protein-delta/genetics , Gene Expression Regulation, Neoplastic/drug effects , Hepatocytes/drug effects , Hepatocytes/metabolism , Interleukin-1beta/pharmacology , NF-kappa B/metabolism , Signal Transduction/drug effects , Apigenin/pharmacology , Binding Sites , CCAAT-Enhancer-Binding Protein-delta/metabolism , Casein Kinase II/antagonists & inhibitors , Cell Line, Tumor , Curcumin/pharmacology , DNA/metabolism , Enzyme Activation/drug effects , Gene Knockdown Techniques , Humans , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Protein Binding/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Time Factors , Transcriptional Activation/drug effects , Transcriptional Activation/genetics
20.
Int J Biochem Cell Biol ; 41(5): 1189-97, 2009 May.
Article in English | MEDLINE | ID: mdl-19027873

ABSTRACT

Tumour necrosis factor-alpha (TNF-alpha) is a key regulator of the immune and inflammatory responses along with numerous other cellular changes during physiological and pathophysiological conditions. The cellular actions of TNF-alpha are associated with both the activation and the inhibition of gene transcription. In contrast to gene activation, the mechanisms underlying the TNF-alpha-mediated transcriptional inhibition remain largely unclear. We have investigated this aspect using the transcription factor CCAAT/enhancer binding protein-alpha (C/EBPalpha) as a model gene. TNF-alpha decreased the expression of C/EBPalpha mRNA and protein in the human hepatoma Hep3B cell line. The activity of the proximal promoter of both the human and the Xenopus C/EBPalpha genes in transfected Hep3B cells was inhibited by TNF-alpha. Transient transfection assays using various Xenopus C/EBPalpha promoter-luciferase DNA constructs showed that a C/EBP recognition sequence was essential for the TNF-alpha response. Electrophoretic mobility shift assays showed that C/EBPalpha bound to this site and co-transfection assays revealed that it was a major activator of the promoter and its transactivation potential was reduced by TNF-alpha. The potential role of nuclear factor kappaB (NF-kappaB) in the response was also investigated in the light of its pivotal role in TNF-alpha signalling. Inhibition of NF-kappaB using pharmacological agents or by transfection of a plasmid specifying for a superrepressor attenuated the TNF-alpha-inhibited C/EBPalpha promoter activity. In addition, an involvement of NF-kappaB in DNA-protein interactions at the C/EBP recognition sequence was identified.


Subject(s)
CCAAT-Enhancer-Binding Protein-alpha/genetics , Hepatocytes/physiology , NF-kappa B/physiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , CCAAT-Enhancer-Binding Protein-alpha/antagonists & inhibitors , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Cell Line, Tumor , Electrophoretic Mobility Shift Assay , Hepatocytes/metabolism , Humans , NF-kappa B/genetics , NF-kappa B/metabolism , NF-kappa B/pharmacology , Promoter Regions, Genetic , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Transfection , Tumor Necrosis Factor-alpha/physiology , Up-Regulation , Xenopus laevis
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