scholarly journals Stimulation of MMP-1 and CCL2 by NAMPT in PDL Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
Andressa Vilas Boas Nogueira ◽  
Per Hoffmann ◽  
Stefan Herms ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
In Vitro Study ◽  
Serum Levels ◽  
Pathogenic Microorganisms ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Pdl Cells ◽  
Increased Risk ◽  
Circulating Levels ◽  
Stimulation Of

Periodontitis is an inflammatory disease caused by pathogenic microorganisms and characterized by the destruction of the periodontium. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), may be a pathomechanistic link between both diseases. The aim of this in vitro study was to examine the regulation of periodontal ligament (PDL) cells by NAMPT and its production under inflammatory and infectious conditions. NAMPT caused a significant upregulation of 9 genes and downregulation of 3 genes, as analyzed by microarray analysis. Eight of these genes could be confirmed by real-time PCR: NAMPT induced a significant upregulation of EGR1, MMP-1, SYT7, ITPKA, CCL2, NTM, IGF2BP3, and NRP1. NAMPT also increased significantly the MMP-1 and CCL2 protein synthesis. NAMPT was significantly induced by interleukin-1βand the periodontal microorganismP. gingivalis. NAMPT may contribute to periodontitis through upregulation of MMP-1 and CCL2 in PDL cells. Increased NAMPT levels, as found in obesity, may therefore represent a mechanism whereby obesity could confer an increased risk of periodontitis. Furthermore, microbial and inflammatory signals may enhance the NAMPT synthesis in PDL cells and thereby contribute to the increased gingival and serum levels of this adipokine, as found in periodontitis.

scholarly journals Regulation of Regenerative Periodontal Healing by NAMPT

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Marjan Nokhbehsaim ◽  
Sema Keser ◽  
Andreas Jäger ◽  
Søren Jepsen ◽  
James Deschner
Keyword(s):  
Periodontal Regeneration ◽  
Enamel Matrix Derivative ◽  
Regenerative Capacity ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Cell Functions ◽  
Periodontal Inflammation ◽  
Pdl Cells ◽  
Increased Risk ◽  
Periodontal Healing

Periodontitis is an inflammatory disease characterized by destruction of the tooth-supporting tissues. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of nicotinamide phosphoribosyltransferase (NAMPT) may be a pathomechanistic link between both diseases. Recently, increased levels of NAMPT have also been found in patients with periodontitis, irrespective of the presence of obesity. This in vitro study sought to examine the effects of NAMPT on the regenerative capacity of human periodontal ligament (PDL) cells and, thereby, periodontal healing. PDL cells treated with enamel matrix derivative (EMD), which was used to mimic regenerative healing conditions in vitro, were grown in the presence and absence of NAMPT for up to 14 d. EMD stimulated significantly (P<0.05) the expression of growth factors and their receptors, matrix molecules, osteogenesis-associated factors, and wound closure and calcium accumulation. In the presence of NAMPT, all these stimulatory effects were significantly (P<0.05) reduced. In conclusion, the beneficial effects of EMD on a number of PDL cell functions critical for periodontal regeneration are counteracted by NAMPT. Enhanced levels of NAMPT, as found in obesity and periodontal inflammation, may compromise the regenerative capacity of PDL cells and, thereby, periodontal healing in the presence of EMD.

Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

2019 ◽  
Vol 25 (22) ◽  
pp. 2474-2479 ◽  
Author(s):  
Alisson Diego Machado ◽  
Gustavo Rosa Gentil Andrade ◽  
Jéssica Levy ◽  
Sara Silva Ferreira ◽  
Dirce Maria Marchioni
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Coronary Artery ◽  
Coronary Artery Calcification ◽  
Serum Levels ◽  
Antioxidant Compounds ◽  
Increased Risk ◽  
Coronary Events ◽  
Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

scholarly journals Genotoxicity and inflammatory potential of stainless steel welding fume particles: an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals

2021 ◽  
Author(s):  
Sarah McCarrick ◽  
Valentin Romanovski ◽  
Zheng Wei ◽  
Elin M. Westin ◽  
Kjell-Arne Persson ◽  
...  
Keyword(s):  
Dna Damage ◽  
In Vitro Study ◽  
Human Monocyte ◽  
Welding Fumes ◽  
Welding Fume ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Cored Wires

AbstractWelders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5–100 µg/mL) and human monocyte-derived macrophages (THP-1, 10–50 µg/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (< 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders.

scholarly journals Irisin and Secondary Osteoporosis in Humans

2022 ◽  
Vol 23 (2) ◽  
pp. 690
Author(s):  
Roberta Zerlotin ◽  
Angela Oranger ◽  
Patrizia Pignataro ◽  
Manuela Dicarlo ◽  
Filippo Maselli ◽  
...  
Keyword(s):  
Mouse Models ◽  
Clinical Evidence ◽  
Bone Fractures ◽  
Secondary Osteoporosis ◽  
Men And Women ◽  
Physiological Relevance ◽  
Increased Risk ◽  
Induced Apoptosis ◽  
Circulating Levels

Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.

scholarly journals The FAM171A2 gene is a key regulator of progranulin expression and modifies the risk of multiple neurodegenerative diseases

2020 ◽  
Vol 6 (43) ◽  
pp. eabb3063
Author(s):  
Wei Xu ◽  
Si-Da Han ◽  
Can Zhang ◽  
Jie-Qiong Li ◽  
Yan-Jiang Wang ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Genome Wide Association Study ◽  
In Vitro Study ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Pathophysiological Role ◽  
Independent Cohort

Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of FAM171A2 were associated with lower CSF PGRN levels (rs708384, P = 3.95 × 10−12). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia and could modify the expression of the FAM171A2 gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that FAM171A2 is a key player in regulating PGRN production.

scholarly journals The Niemann-Pick C1 Like 1 (NPC1L1) Inhibitor Ezetimibe Improves Metabolic Disease Via Decreased Liver X Receptor (LXR) Activity in Liver of Obese Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2810-2819 ◽  
Author(s):  
Taichi Sugizaki ◽  
Mitsuhiro Watanabe ◽  
Yasushi Horai ◽  
Nao Kaneko-Iwasaki ◽  
Eri Arita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Insulin Signaling ◽  
Metabolic Diseases ◽  
In Vitro Study ◽  
Liver X Receptor ◽  
Gene Expressions ◽  
The Metabolic Syndrome ◽  
Increased Risk

Dyslipidemic patients with diabetes mellitus, including metabolic syndrome, are at increased risk of coronary heart disease. It has been reported that ezetimibe, a cholesterol absorption inhibitor, improves metabolic diseases in mice and humans. However, the underlying mechanism has been unclear. Here we explored the effects of ezetimibe on lipid and glucose homeostasis. Male KK-Ay mice were fed a high-fat diet, which is the mouse model of metabolic syndrome, with or without ezetimibe for 14 weeks. Ezetimibe improved dyslipidemia, steatosis, and insulin resistance. Ezetimibe decreased hepatic oxysterols, which are endogenous agonists of liver X receptor (LXR), to decrease hepatic lipogenic gene expressions, especially in stearoyl-CoA desaturase-1 (SCD1), leading to a remarkable reduction of hepatic oleate content that would contribute to the improvement of steatosis by reducing triglycerides and cholesterol esters. Simultaneously, hepatic β-oxidation, NADPH oxidase and cytochrome P450 2E1 (CYP2E1) were reduced, and thus reactive oxygen species (ROS) and inflammatory cytokines were also decreased. Consistent with these changes, ezetimibe diminished c-Jun N-terminal kinase (JNK) phosphorylation and improved insulin signaling in the liver. In vitro study using primary hepatocytes obtained from male SD rats, treated with oleate and LXR agonist, showed excess lipid accumulation, increased oxidative stress and impaired insulin signaling. Therefore, in obese subjects, ezetimibe reduces hepatic LXR activity by reducing hepatic oxysterols to lower hepatic oleate content. This improves steatosis and reduces oxidative stress, and this reduction improves insulin signaling in the liver. These results provide insight into pathogenesis and strategies for treatment of the metabolic syndrome.

scholarly journals Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 284
Author(s):  
John H. White
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
Antimicrobial Peptides ◽  
Active Form ◽  
Cytokine Network ◽  
Increased Risk ◽  
Tract Infections ◽  
Circulating Levels

Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.

Interleukin-1 beta release from rat gastric fundus

1996 ◽  
Vol 271 (2) ◽  
pp. G275-G281 ◽  
Author(s):  
P. Montuschi ◽  
G. Tringali ◽  
A. Mirtella ◽  
L. Parente ◽  
E. Ragazzoni ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Ex Vivo ◽  
Interleukin 1 ◽  
Gastric Fundus ◽  
Interleukin 1 Beta ◽  
Rat Gastric Fundus ◽  
Hypothalamic Level ◽  
Stimulation Of

Interleukin-1 (IL-1) is known to regulate gastric functions via a central action at the hypothalamic level, and it has also been shown that this cytokine can directly modulate rat gastric motility. This study was conducted to determine whether IL-1 beta is produced and released by rat gastric fundi in vitro. IL-1 beta immunoreactivity was released in measurable amounts from explanted rat gastric tissue. This release was not affected by electrical stimulation of the gastric strips or by agents that induce IL-1 biosynthesis. It could be inhibited only by the glucocorticoid dexamethasone. Ex vivo experiments confirmed the inhibitory role of glucocorticoids and showed that IL-1 beta release can be inhibited by agents that reduce gastric acid secretion, suggesting that the latter might stimulate IL-1 beta synthesis and release. In light of the well-established gastroprotection exerted by IL-1, H(+)-induced IL-1 beta release might serve as a protection against mucosal injuries caused by acid secretion, and the inhibition of this release by glucocorticoids might be involved in the pathogenesis of gastric damage associated with severe stress or steroid therapy.

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