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Summary: Purpose: Older adults have a higher risk of malnutrition and hospitalization and, likewise, malnutrition can be a risk factor for hospitalization. The purpose of the present study was to determine the possible association between malnutrition and hospitalization in older adults at the Naval Medical Center “Cirujano Mayor Santiago Távara'' in Peru. Patients and Methods: A cross-sectional analytical study was conducted in older adults over 60 years of age attended by the outpatient and Day Clinic during the period 2010–2015. Malnutrition was assessed using the Mini Nutritional Assessment scale. Multivariate analysis of the association between malnutrition and hospitalization with control of confounding variables was performed using a Poisson regression model with robust variance, obtaining an adjusted prevalence ratio (aPR). Results: The study included 1865 older adults. 58.7% were male, and 46% were between 70 and 80 years of age. 16.3% had malnutrition, 80.6% had at least one emergency department visit, and 35.6% were hospitalized at least once. Multivariate analysis showed a statistically significant association between malnutrition and hospitalization (aPR = 3.22; 95% confidence interval [CI]: 2.56–4.03), as well as between depressive symptoms and hospitalization (aPR = 1.54; 95% CI: 1.23–1.93). On the other hand, emergency department visits were associated with a lower frequency of hospitalization (aPR = 0.70; 95% CI: 0.54–0.90). Conclusion: Malnutrition and depressive symptoms were associated with hospitalization in retired naval personnel and their families at the Naval Medical Center, while emergency department visits constituted a protective factor.

Purpose: To compare intensity-modulated proton therapy with CyberKnife (CK) therapy for hypo-fractionated treatments of prostate with focal boost, as a first planning study for prostate with dose escalation to a dominant intraprostatic lesion (DIL)., Materials and Methods: Ten patients who possess one DIL in their prostate and their CK plans that were used to treat the planning target volume of prostate were chosen. Six of the plans were further escalated to DIL. Intensity-modulated proton therapy plans were created for the patients with robust optimization, accounting for setup and range uncertainties for the clinical target volume (CTV) of prostate. The CK plans were then compared with the proton plans., Results: In the worst scenario of the robust evaluation, the proton plans reasonably met all objectives and constraints used in CK planning for both CTV coverage and organs-at-risk (OAR) sparing. Under the nominal scenario of the robust optimization, the proton plans produced dosimetric values comparable to those by the CK plans for both CTV and DIL coverage. The average dose to CTV, outside DIL and urethra, was found lower in the proton plans than in the CK plans due to the uncertainties. A similar trend was observed for the dose conformity to CTV. These two findings, however, were not planning objectives. Regarding organs-at-risk sparing, the proton plans in the nominal scenario were comparable to the CK plans for doses >18.125 Gy; for doses below it, the proton performed better. This study offers a basis for a clinical trial of treatment of prostate cancer by proton that may be transferred from the CK system in our center., Conclusion: The dosimetric objectives and constraints used in the CK plans were achieved with the proton plans., (© 2024 The Author(s).)

Initial chronic obstructive lung disease (COPD) pharmacotherapy is based on symptom burden and exacerbation history. Inclusion of inhaled cortico-steroids (ICS) is recommended only for those with a history of exacerbations. This brief report highlights that among individuals with previously unrecognized COPD about 1 in 5 have one or more exacerbation-like events and about 1 in 10 have two or more events in the prior 12 months whether or not they self-report concomitant asthma. Closer attention to prior exacerbation-like event history might lead to more guideline concordant care. In addition, there are two other groups that have impaired but non-obstructive spirometry, some with significant respiratory symptom burden who have frequencies of exacerbation-like events similar to those meeting COPD spirometry criteria. To date we have little guidance for treatment of these individuals., Competing Interests: Declaration of competing interest Dr. Martinez reports grants from NHLBI Sponsor of the parent trial, grants from COPD Foundation Organizes the financial contributions of Industry Advisory Consortium, grants from AstraZeneca Member of the CAPTURE Industry Advisory Consortium, grants from Boehringer Ingelheim Member of the CAPTURE Industry Advisory Consortium, grants from GlaxoSmithKline Member of the CAPTURE Industry Advisory Consortium, grants from Sunovion Member of the CAPTURE Industry Advisory Consortium, grants from Teva Member of the CAPTURE Industry Advisory Consortium, and grants from Viatris Member of the CAPTURE Industry Advisory Consortium during the conduct of the study; grants from AstraZeneca Study Steering Committee, personal fees from AstraZeneca Advisory Boards, disease state presentations, non-financial support from AstraZeneca Travel to meetings, grants from Boehringer Ingelheim Steering Committee of ILD study, personal fees from Boehringer Ingelheim COPD and ILD Advisory Boards, personal fees from Boehringer Ingelheim ILD disease state presentation, non-financial support from Boehringer Ingelheim Travel to meetings, grants from Chiesi COPD Steering Committee, non-financial support from Chiesi including travel to meeting, grants from Csl Behring COPD Advisory Board, nonfinancial support from Csl Behring Travel to meeting, grants from GlaxoSmithKline COPD Study Steering Committee, personal fees from GlaxoSmithKline COPD Advisory Boards, personal fees from GlaxoSmithKline COPD disease state presentations, non-financial support from GlaxoSmithKline Travel to meetings, other from GlaxoSmithKline COPD Study DSMB, grants from Medtronic COPD study adjudication committee, grants from Novartis COPD Study Steering Committee, grants from Novartis COPD Advisory Boards, grants from Polarean COPD Advisory Board, other from Pulmatrix COPD tele consultation, other from Polarean COPD tele consultation, grants from Sanofi/Regeneron COPD Study Steering Committee, personal fees from Sanofi/Regeneron COPD Advisory Board, and personal fees from Theravance/Viatris COPD Advisory Board outside the submitted work; in addition, Dr. Martinez has a patent for CAPTURE licensed to Weill Cornell. Ms. Anderson has nothing to disclose. Dr. Brown reports personal fees from Teva outside the submitted work Dr Dolor reports grants from NIH 1R01 HL136682 and grants from COPD Foundation during the conduct of the study. Dr. Elder reports grants from national institutes of health during the conduct of the study. Dr. Han reports grants from NIH and grants from COPD Foundation during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from AstraZeneca sponsored research, funds paid to institution, personal fees from Verona, personal fees from Merck, personal fees from MDBriefcase, personal fees from Mylan, other from Sanofi sponsored research, funds paid to institution, personal fees from DevPro, personal fees from Aerogen, personal fees from Polarean, personal fees from Regeneron, personal fees from UpToDate, personal fees from Altesa Pharmaceuticals, personal fees from Medscape, personal fees from Integrity, non-financial support from Sunovion, grants from American Lung Association, grants from COPD Foundation, other from Biodesix sponsored research, funds paid to institution, other from Gala Therapeutics sponsored research, funds paid to institution, other from Nuvaira sponsored research, funds paid to institution, personal fees from Boehringer Ingelheim, personal fees from Cipla, personal fees from Chiesi, other from Novartis DSMB with funds paid to institution and drug for trial, personal fees from Pulmonx, personal fees from Teva, other from AstraZeneca sponsored research, funds paid to institution, grants from Boehringer Ingelheim, other from Sanofi sponsored research, funds paid to institution, personal fees from NACE, other from Medtronic DSMB with funds paid to institution, other from Altesa Pharmaceuticals stock options, and other from Meissa Vaccines stock options outside the submitted work. Dr. Joo reports grants from NIH and grants from COPD Foundation during the conduct of the study. Dr. Khan reports other from Circuit Clinical Standard Clinical Trial Site and Enrollment Fees were paid for study execution to the clinical trials company of which I am CEO during the conduct of the study. Dr. Knox has nothing to disclose. Ms. Angulo has nothing to disclose. Mr. Lopez has nothing to disclose. Dr. Make reports grants from NHLBI Research grant funds provided to and controlled by National Jewish Health. Grant review study section., grants from American Lung Association Research grant funds to and controlled by National Jewish Health., grants from Department of Defense Research grant funds provided to and controlled by National Jewish Health, other from Astra Zeneca Medical Advisory Board. Disease-state presentation. Research grant funds provided to and controlled by National Jewish Health. Consultant for data analysis. Steering Committee for NOVELTY observational study. other from Spiration Reviewed clinical trial data. Data and Safety Monitoring Board., other from Glaxo Smith Kline Advisory Board member. Disease-state presentation., other from Boehringer Ingelheim Medical Advisory Board, other from Mylan Medical Advisory Board, other from Quintiles Data Safety and Monitoring Board, other from University of Wisconsin Data Safety and Monitoring Board, and other from Mt. Sinai CME activity. Data and Safety Monitoring Board. during the conduct of the study; personal fees from Web MD CME activity, personal fees from Novartis CME activity, personal fees from American College of Chest Physicians CME activity, personal fees from Projects in Knowledge CME activity, personal fees from Third Pole Consultant for proposed trial, personal fees from Optimum Patient Care Global Limited Consultant, and personal fees from Integritas Communications CME activity outside the submitted work; in addition, Dr. Make has a patent for Wolters Kluwer Health (Up-To-Date) with royalties paid Royalties. Dr. Mannino reports personal fees from GlaxoSmithKline, personal fees from AstraZeneca, personal fees from Up-to-Date, and personal fees from Schlesinger Law Firm outside the submitted work. Ms. Meldrum has nothing to disclose. Dr. Murray reports grants from NIH during the conduct of the study. Ms. Peters has nothing to disclose Dr. Spino reports grants from NIH and grants from Three Lakes Foundation during the conduct of the study. Dr. Tapp has nothing to disclose. Dr. Thomashow reports grants from NHLBI during the conduct of the study; personal fees from GSK consultant, personal fees from Boehringer Ingelheim advisory board, and personal fees from Reckitt Health consultant outside the submitted work; and cofounder and chief medical officer (volunteer position) COPD Foundation, a non for profit. Dr. Yawn reports grants from National Heart Lung and Blood Institute and personal fees from COPD Foundation during the conduct of the study; personal fees from GSK COPD and Herpes Zoster, investigator initiated grant and COPD advisory board and consulting, personal fees from TEVA Advisory board and consulting, personal fees from AZ Advisory board and consulting, and personal fees from BI Consulting outside the submitted work. Dr. Zittleman has nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: We compared the analgesic efficacy of a continuous suprascapular nerve block (C-SSNB) and a single-shot interscalene brachial plexus block (S-ISNB) for postoperative pain management in patients undergoing arthroscopic rotator cuff repair., Methods: A total of 118 patients undergoing arthroscopic rotator cuff repair were randomly allocated to the S-ISNB or C-SSNB groups. Postoperative pain was assessed using the visual analog scale (VAS) at 1, 2, 6, 12, and 24 h postoperatively. Supplemental analgesic use was recorded as total equianalgesic fentanyl consumption., Results: The C-SSNB group showed significantly higher VAS scores at 0-1 h and 1-2 h after the surgery than the S-ISNB group (4.9±2.2 versus 2.3±2.2; p<0.0001 and 4.8±2.1 versus 2.4±2.3; p<0.0001, respectively). The C-SSNB group showed significantly lower VAS scores at 6-12 h after the surgery than the S-ISNB group (4.1±1.8 versus. 5.0±2.5; p=0.031). The C-SSNB group required significantly higher doses of total equianalgesic fentanyl in the post-anesthesia care unit than the S-ISNB group (53.66±44.95 versus 5.93±18.25; p<0.0001). Total equianalgesic fentanyl in the ward and total equianalgesic fentanyl throughout the hospital period were similar between the groups (145.99±152.60 versus 206.13±178.79; p=0.052 and 199.72±165.50 versus 212.15±180.09; p=0.697, respectively)., Conclusion: C-SSNB was more effective than S-ISNB at 6-12 h after the surgery for postoperative analgesia after arthroscopic rotator cuff repair.

Background: Experiencing difficulties and challenges though COVID-19 pandemic, there are voices that it needs to be discussed to seek direction of basic research and college education of Korean Medicine (KM) so that KM community can play a significant role in the future infectious disease outbreaks., Methods: This paper summarizes the edited highlights of an online video meeting by Google meet on May 19, 2020, organized by the Korean Medicine Convergence Research Information Center. Five researchers specialized in immunology, microbiology, virology, preventive medicine, and herbology, respectively, presented what KM community should prepare for the future acute infectious disease outbreaks by learning from the previous research on antiviral effect of herbs for coronavirus and the experiences of the present COVID-19 pandemic., Results: There are a lot of herbs or natural products with potential anti-coronavirus effects reported from in vitro experiments and despite criticism, many clinical trials on traditional herbal medicine for COVID-19 are being conducted. In addition to establishing research evidence, KM community should train and produce public health professionals among Korean Medicine Doctors (KMDs) and official participation in public healthcare system should be ensured in terms of regulation and policy. Newly developed KM treatments can be interpreted by the KM theories and also should be allowed by regulations for KMDs to utilize them., Conclusion: The present online discussion suggested directions of basic research for acute viral infections diseases utilizing KM and how to enforce relevant education and regulations in the post-COVID-19 era., (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

Aflatoxin B 1 (AFB 1 ) is a carcinogenic substance produced by fungi of genus Aspergillus, especially Aspergillus flavus. Few nanograms of AFB 1 that permeated through the skin is sufficient to cause liver cancer and stunted growth. In this study, a rapid aptamer-based assay for AFB 1 was developed using the fluorescence quenching property of graphene oxide (GO) and a fluorescein amidite (FAM)-modified aptamer specific to AFB 1 . The aptamer, modified with the fluorescence dye FAM on its 5'-end, was used as a probe. Once bound by AFB 1 , a conformational change of the aptamer was caused that led to its interaction with the well-known fluorescence quencher GO, resulting in a decrease of the fluorescence intensity of the system. In the absence of AFB 1 , the fluorescence intensity remained unchanged. The aptamer-based AFB 1 assay process was conducted through 3 steps within 40min. The aptamer was incubated with AFB 1 before the addition of GO. The amount of AFB 1 present was measured by the change in fluorescence intensity. The detection system was evaluated with standard solutions of AFB 1 of various concentrations. The results showed that the fluorescence intensity decreased linearly as the concentration of AFB 1 gradually increased. Although the assay was specific to AFB 1 , there was slight interference by other types of aflatoxin. When the assay was applied to a real sample, the limit of detection was 4.5 ppb, which was within the wide detection range of up to 300ppb with good linearity. Thus, this biosensor is considered to be competitive with the conventional detection methods in the field owing to its wide detection range and assay rapidity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ambient cold temperature, as an abiotic stress, regulates the survival, stability, transmission, and infection of pathogens. However, the effect of cold temperature on the host receptivity to the pathogens has not been fully studied. In this study, the expression of terminal α-2,3- and α-2,6-sialic acids were increased in murine lung tissues, especially bronchial epithelium, by exposure to cold condition. The expression of several sialyltransferases were also increased by exposure to cold temperature. Furthermore, in human bronchial epithelial BEAS-2B cells, the expressions of α-2,3- and α-2,6-sialic acids, and mRNA levels of sialyltransferases were increased in the low temperature condition at 33 °C. On the other hand, the treatment of Lith-Gly, a sialyltransferase inhibitor, blocked the cold-induced expression of sialic acids on surface of BEAS-2B cells. The binding of influenza H1N1 hemagglutinin (HA) toward BEAS-2B cells cultured at low temperature condition was increased, compared to 37 °C. In contrast, the cold-increased HA binding was blocked by treatment of lithocholicglycine and sialyl-N-acetyl-D-lactosamines harboring α-2,3- and α-2,6-sialyl motive. These results suggest that the host receptivity to virus at cold temperature results from the expressions of α-2,3- and α-2,6-sialic acids through the regulation of sialyltransferase expression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Kaurenoic acid (ent-kaur-16-en-19-oic acid: KA) is a key constituent found in the roots of Aralia continentalis Kitagawa (Araliaceae), a remedy to treat patients with inflammatory diseases in traditional Asian medicine. Since KA activates Nrf2, a key anti-inflammatory factor, at the cellular level, we explored a possible therapeutic usage of KA against neutrophilic inflammatory lung disease such as acute lung injury (ALI). Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) to C57BL/6 mice induced lung inflammation as in ALI. 2 h after i.p. LPS, intratracheal (i.t.) delivery of KA (0.3, 3, or 30 μg/kg body weight) improved lung structure and significantly suppressed neutrophil infiltrations to mouse lungs, with concomitant reduction of myeloperoxidase activity and of the expression of pro-inflammatory cytokine genes. While activating Nrf2 and expressing Nrf2-dependent genes in mouse lungs, KA did not significantly suppress neutrophil lung inflammation in Nrf2 KO mice. In a mouse model of sepsis, a major cause of ALI, single i.t. KA (3 μg/kg) 2 h after the onset of sepsis significantly decreased the mortality of mice. Together, these results suggest that KA has a therapeutic potential against inflammatory lung disease, the effect of which is associated with Nrf2 activation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Fibromatosis of the breast, also known as a desmoid tumor, is extremely rare and most often appears as an aggressive lesion mimicking breast carcinoma. It lacks metastatic potential but can grow aggressively in a localized area. Ultrasonography often shows an irregular spiculated hypoechoic mass with posterior acoustic shadowing. We discuss a case of breast fibromatosis that presented as a painful palpable breast mass in a 32-year-old woman and mimicked an abscess in the sonogram. We found that this lesion displayed atypical sonographic features such as a heterogeneous echoic mass with an internal anechoic area., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Metastasis is major cause of malignant cancer-associated mortality. Fucoxanthin has effect on various pharmacological activities including anti-cancer activity. However, the inhibitory effect of fucoxanthin on cancer metastasis remains unclear. Here, we show that fucoxanthin isolated from brown alga Saccharina japonica has anti-metastatic activity. To check anti-metastatic properties of fucoxanthin, in vitro models including assays for invasion, migration, actin fiber organization and cancer cell-endothelial cell interaction were used. Fucoxanthin inhibited the expression and secretion of MMP-9 which plays a critical role in tumor invasion and migration, and also suppressed invasion of highly metastatic B16-F10 melanoma cells as evidenced by transwell invasion assay. In addition, fucoxanthin diminished the expressions of the cell surface glycoprotein CD44 and CXC chemokine receptor-4 (CXCR4) which play roles in migration, invasion and cancer-endothelial cell adhesion. Fucoxanthin markedly suppressed cell migration in wound healing assay and inhibited actin fiber formation. The adhesion of B16-F10 melanoma cells to the endothelial cells was significantly inhibited by fucoxanthin. Moreover, in experimental lung metastasis in vivo assay, fucoxanthin resulted in significant reduction of tumor nodules. Taken together, we demonstrate, for the first time, that fucoxanthin suppresses metastasis of highly metastatic B16-F10 melanoma cells in vitro and in vivo., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Advanced glycation end-products (AGEs) play a pivotal role in the development of diabetic complications by inducing inflammation. We previously reported that the fresh roots of Rehmannia glutinosa Libosch., which have been used for the treatment of diabetes in traditional Korean medicine, also have the potential to suppress AGE-mediated inflammatory response in THP-1 cells. In the present study, we isolated catalpol from R. glutinosa, and examined whether it has anti-inflammatory effects on AGE-stimulated THP-1 cells. Catalpol reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE). Promoter and electromobility shift assays showed that transcriptional activation of NF-κB was significantly reduced by catalpol treatment, while AP-1 was not. Catalpol also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of IκBα and the nuclear localization of NF-κB. Moreover, the production of intracellular reactive oxygen species (ROS) elicited by AGE was also suppressed by catalpol treatment, through dual action of reducing ROS itself and inhibiting NADPH oxidase activity. Our findings indicate that catalpol suppresses AGE-mediated inflammation by inhibiting ROS production and NF-κB activity. We suggest that catalpol, a major constituent of the fresh roots of R. glutinosa, contributes to the prevention of AGE-mediated diabetic complications., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a member of the immunoglobulin superfamily expressed on macrophage and neutrophils and is emerging as a potent amplifier of TLR initiated inflammatory responses. Blockade of TREM-1 improves survival in animal models of sepsis. In this study, we show that curcumin or diferuloylmethane, a yellow pigment present in turmeric, a major ingredient of curry spice inhibited the expression of TREM-1 in vitro in primary bone marrow derived macrophages and in vivo in lungs of mice with sepsis. Chromatin immunoprecipitation assay confirmed that curcumin inhibits the binding of p65 to TREM-1 promoter in response to LPS. Further we show that curcumin inhibited p300 activity in the TREM-1 promoter region leading to hypoacetylation of histone 3 and 4 in the lysine residues. Inhibition of TREM-1 by curcumin is oxidant independent. These studies are the first report to define a detailed molecular mechanism by which curcumin exerts anti-inflammatory effects through regulation of TREM-1 gene activity and provide additional mechanistic insights into the anti-inflammatory effect of curcumin., (Published by Elsevier Ltd.)

Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose β-1,4-N-acetylglucosamine (Galβ1-4GlcNAc) groups on N-linked sugar chains of glycoproteins, which play important roles in many biological events, including the proliferation and migration of cancer cells. A previous microarray study reported that this gene is expressed by estrogen treatment in breast cancer. In this study, we examined the regulatory mechanisms and biological functions of estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced expression of B4GALT1 is localized in intracellular compartments and in the plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the production of the Galβ1-4GlcNAc structure. The result from a promoter assay and chromatin immunoprecipitation revealed that 3 different estrogen response elements (EREs) in the B4GALT1 promoter are critical for responsiveness to estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-α-ERE binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However, the inhibition of signal molecules relating to the extra-nuclear pathway, including the G-protein coupled receptors, Ras, and mitogen-activated protein kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the significant inhibition of estrogen-induced proliferation of MCF-7 cells. Considering these results, we propose that estrogen regulates the expression of B4GALT1 through the direct binding of ER-α to ERE and that the expressed B4GALT1 plays a crucial role in the proliferation of MCF-7 cells through its activity as a membrane receptor., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The Great Barrier Reef (GBR) catchment area has been monitored simultaneously for sediment and nutrient exports from 10 priority catchments discharging into the GBR lagoon between 2006 and 2009. This allows GBR catchment-wide exports to be estimated and spatially compared within a discrete time-frame. Elevated levels of sediment and nutrient exports were recorded in all monitored catchments as compared to pre-European estimates, but vary around previous estimates of mean annual loads. During the period of monitoring, the Burdekin and Fitzroy catchments contributed the highest sediment and nutrient exports, however when loads were normalised for area, these catchments produced the lowest unit yields. In contrast, the highest yields were produced in the wetter and proportionately more intensively cultivated Johnstone, O'Connell, and Pioneer catchments particularly for dissolved nitrogens. This assessment offers the necessary scientific foundation for future monitoring, assessment, and management of sediment and nutrient loads entering the GBR., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

If not controlled properly, inflammatory response is often detrimental. However, in many cases, it can be self-limited and subsides without inflicting tissue damage. In this study, we tested the hypothesis that inflammatory stimuli can trigger anti-inflammatory response, which may contribute to limiting tissue damage induced by excessive inflammation. We found that treatment of bone marrow-derived macrophages with lipopolysaccharide (LPS) activated NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor that regulates inflammation, leading to expression of Nrf2-regulated genes including NAD(P)H:quinine oxidoreductase 1,glutamyl cysteine ligase catalytic unit and heme oxygenase-1. Suppression of Nrf2 by siRNA significantly diminished the expression of the Nrf2-regulated genes induced by LPS. By using pharmacological, genetic and epigenetic analyses, we found that activation of Nrf2 in response to LPS is dependent on MyD88 but independent of the production of reactive oxygen species. Together, our results show that activation of Nrf2 by MyD88 dependent signaling induced by LPS is an important intrinsic mechanism that limits excessive inflammation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

PU.1, an Ets family transcription factor, mediates macrophage effector function in inflammation by regulating gene expression. But, the extent and nature of PU.1 function in gene expression has not been genetically determined because ablation of PU.1 gene abolishes macrophage development. Here, we epigenetically suppressed PU.1 by stably expressing PU.1 specific siRNA in macrophages, and determined the effect of PU.1 deficiency on expressions of key inflammatory genes: Toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX-2), and macrophage inflammatory protein-1alpha (MIP-1alpha). PU.1-silenced cell lines expressed lower TLR4 mRNA and COX-2 protein, but higher MIP-1alpha protein, than controls. Over-expression of PU.1 suppressed lipopolysaccharide-induced MIP-1alpha production. PU.1 occupied proximal and distal cognate sites in the endogenous MIP-1alpha promoter, but dissociated only from the distal sites in response to lipopolysaccharide, suggesting a novel negative regulatory mechanism by PU.1. Together, our results defined PU.1 function in differentially regulating expressions of TLR4, COX-2, and MIP-1alpha.