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https://www.readbyqxmd.com/read/28526706/cardiac-hyporesponsiveness-in-severe-sepsis-is-associated-with-nitric-oxide-dependent-activation-of-g-protein-receptor-kinase
#1
Daniela Dal-Secco, Silvia DalBó, Natalia E S Lautherbach, Fábio N Gava, Mara Rubia Nunes Celes, Patricia Oliveira Benedet, Adriana H Souza, Juliana Akinaga, Vanessa Lima, Katiussia P Silva, Luiz Ricardo A Kiguti, Marcos A Rossi, Isis do Carmo Kettelhut, André Sampaio Pupo, Fernando Queiroz Cunha, Jamil Assreuy
G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS-2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP)...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28525390/microrna-155-attenuates-late-sepsis-induced-cardiac-dysfunction-through-jnk-and-%C3%AE-arrestin-2
#2
Yu Zhou, Yan Song, Zahir Shaikh, Hui Li, Haiju Zhang, Yi Caudle, Shouhua Zheng, Hui Yan, Dan Hu, Charles Stuart, Deling Yin
Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP)...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524264/maternal-occupational-physical-activity-and-risk-for-orofacial-clefts
#3
A J Agopian, Jihye Kim, Peter H Langlois, Laura Lee, Lawrence W Whitehead, Elaine Symanski, Michele L Herdt, George L Delclos
OBJECTIVES: To perform a case-control study of maternal occupational physical activity and risk for orofacial clefts in Texas during 1999-2009. METHODS: We used logistic regression to assess 14 measures of physical activity estimated from a job exposure matrix, using the maternal occupation reported on the birth certificate, among 887 children with cleft lip with or without cleft palate (CLP), 436 children with cleft palate only (CP), and 1932 controls. RESULTS: After adjusting for several potential confounders, seven measures of physical activity (as a categorical and/or continuous variable) were significantly associated with CLP, CP, or both...
May 19, 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28523271/the-protein-chaperone-clpx-targets-native-and-non-native-aggregated-substrates-for-remodeling-disassembly-and-degradation-with-clpp
#4
Christopher J LaBreck, Shannon May, Marissa G Viola, Joseph Conti, Jodi L Camberg
ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28515693/rolipram-improves-outcome-in-a-rat-model-of-infant-sepsis-induced-cardiorenal-syndrome
#5
Clark R Sims, Sharda P Singh, Shengyu Mu, Neriman Gokden, Dala Zakaria, Trung C Nguyen, Philip R Mayeux
While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28513569/intravenous-arginine-administration-promotes-proangiogenic-cells-mobilization-and-attenuates-lung-injury-in-mice-with-polymicrobial-sepsis
#6
Chiu-Li Yeh, Man-Hui Pai, Yao-Ming Shih, Juey-Ming Shih, Sung-Ling Yeh
This study investigated the influence of intravenous arginine (Arg) administration on alteration of circulating proangiogenic cells and remote lung injury in a model of polymicrobial sepsis. Mice were assigned to one normal control group (NC) and two sepsis groups that were induced by cecal ligation and puncture (CLP). One of the sepsis groups was injected with saline (SS), whereas the other (SA) was administered with a single bolus of 300 mg Arg/kg body weight via the tail vein 1 h after CLP. Septic mice were sacrificed at either 24 or 48 h after CLP, with their blood and lung tissues collected for analysis...
May 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28508944/suppressive-effects-of-zingerone-on-tgfbip-mediated-septic-responses
#7
Gahee Min, Sae-Kwang Ku, Taeho Lee, Jong-Sup Bae
Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess various pharmacological activities. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells and functions as a mediator of experimental sepsis. We hypothesized that ZGR could reduce TGFBIp-mediated severe inflammatory responses in human endothelial cells and mice...
May 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28507543/long-term-monocyte-dysfunction-after-sepsis-in-humanized-mice-is-related-to-persisted-activation-of-macrophage-colony-stimulation-factor-m-csf-and-demethylation-of-pu-1-and-it-can-be-reversed-by-blocking-m-csf-in-vitro-or-by-transplanting-na%C3%A3-ve-autologous
#8
Natalia Lapko, Mateusz Zawadka, Jacek Polosak, George S Worthen, Gwenn Danet-Desnoyers, Monika Puzianowska-Kuźnicka, Krzysztof Laudanski
The duration of post-sepsis long-term immune suppression is poorly understood. Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several acute conditions, but it is unclear for how long MO aberrancy post-sepsis can persist. Interestingly, the positive feedback loop sustaining secretion of macrophage-colony stimulation factor (M-CSF) can persist even after resolution of sepsis and significantly alters performance of MO...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28505020/the-role-of-thioredoxin-1-in-suppression-sepsis-through-inhibiting-mitochondrial-induced-apoptosis-in-spleen
#9
Guobing Chen, Xiang Li, Mengbing Huang, Xiaoshuang Zhou, Ye Li, Xiaoqin Mao, Jie Bai
Sepsis is a serious public health issue and the leading cause of death in critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a protein of regulating redox, as well as a modulator of inflammation and apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum-mediated inflammation involved in lung in a model of experimental sepsis. However, its effect on mitochondrial-mediated apoptosis in spleen has not been reported. We studied whether Trx-1 could prevent spleen cells apoptosis in sepsis...
June 2017: Shock
https://www.readbyqxmd.com/read/28503576/sirtuin-2-regulates-microvascular-inflammation-during-sepsis
#10
Nancy Buechler, Xianfeng Wang, Barbara K Yoza, Charles E McCall, Vidula Vachharajani
Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1-7), epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT), SIRT2 knockout (SIRT2KO), and SIRT2 overexpressing (SIRT2KI) mice by cecal ligation and puncture (CLP)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28501779/coenzyme-q10-improves-the-survival-mesenteric-perfusion-organs-and-vessel-functions-in-septic-rats
#11
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Ibrahim Kilinc, Sultan Pehlivan, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28501568/polytrauma-induced-hepatic-stress-response-and-the-development-of-liver-insulin-resistance
#12
Robert M Akscyn, J Lee Franklin, Tatyana A Gavrikova, Joseph L Messina
Insulin resistance and metabolic dysfunction are common following injury. Polytrauma is defined as combined injuries to more than one body part or organ system, and is common in modern warfare, as well as automobile and industrial accidents. Polytrauma can include any combination of burn injury, fracture, hemorrhage, trauma to the extremities, and blunt or penetrating trauma. Multiple minor injuries are often more deleterious than a more severe single injury. To investigate the mechanisms of development of insulin resistance following injury, we have developed a rat model of polytrauma which combined soft tissue trauma with burn injury and penetrating gastrointestinal (GI) trauma...
May 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28498297/gastrointestinal-colonization-of-candida-albicans-increases-serum-1%C3%A2-3-%C3%AE-d-glucan-without-candidemia-and-worsens-cecal-ligation-and-puncture-sepsis-in-murine-model
#13
Wimonrat Panpetch, Naraporn Somboonna, Dewi Embong Bulan, Jiraphorn Issara-Amphorn, Navaporn Worasilchai, Malcolm Finkelman, Ariya Chindamporn, Tanapat Palaga, Somying Tumwasorn, Asada Leelahavanichkul
The role of intestinal Candida albicans in bacterial sepsis, in the absence of candidemia, was investigated in murine models. Live C. albicans or normal saline solution (NSS) was administered orally once, followed by 5 days of daily oral antibiotic-mixtures (ATB). Cecal ligation and puncture (CLP) was then performed to induce sepsis.Fecal Candida was detected by culture only in models with Candida administration. Oral Candida administration with/without ATB enhanced gut-pathogenic bacteria as determined by microbiome analysis...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28497397/xuebijing-injection-and-resolvin-d1-synergize-to-regulate-leukocyte-adhesion-and-improve-survival-rate-in-mice-with-sepsis-induced-lung-injury
#14
Shu-Kun Zhang, Yu-Zhen Zhuo, Cai-Xia Li, Lei Yang, Hong-Wei Gao, Xi-Mo Wang
OBJECTIVES: To investigate the effect of combined application of Xuebijing Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. METHODS: The cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specifific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 μL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28490437/high-throughput-crispri-phenotyping-identifies-new-essential-genes-in-streptococcus-pneumoniae
#15
Xue Liu, Clement Gallay, Morten Kjos, Arnau Domenech, Jelle Slager, Sebastiaan P van Kessel, Kèvin Knoops, Robin A Sorg, Jing-Ren Zhang, Jan-Willem Veening
Genome-wide screens have discovered a large set of essential genes in the opportunistic human pathogen Streptococcus pneumoniae However, the functions of many essential genes are still unknown, hampering vaccine development and drug discovery. Based on results from transposon sequencing (Tn-seq), we refined the list of essential genes in S. pneumoniae serotype 2 strain D39. Next, we created a knockdown library targeting 348 potentially essential genes by CRISPR interference (CRISPRi) and show a growth phenotype for 254 of them (73%)...
May 10, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28485787/pachymic-acid-improves-survival-and-attenuates-acute-lung-injury-in-septic-rats-induced-by-cecal-ligation-and-puncture
#16
J-Y Li, H-X Wu, G Yang
OBJECTIVE: The purpose of this study was to elucidate the possible beneficial effects of pachymic acid (PA) on acute lung injury (ALI) in a rat model of sepsis. MATERIALS AND METHODS: A rat model of sepsis induced by cecal ligation and puncture (CLP) was used. Rats were randomly divided into five groups: sham, CLP, CLP + PA 1 mg/kg, CLP + PA 5 mg/kg, CLP + PA 10 mg/kg. CLP + PA groups received PA by intraperitoneal injection daily for consecutive 3 days, respectively, and the rats in sham and CLP groups were given equivalent volume of olive oil...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28485784/pachymic-acid-ameliorates-sepsis-induced-acute-kidney-injury-by-suppressing-inflammation-and-activating-the-nrf2-ho-1-pathway-in-rats
#17
Z-Y Cai, Z-X Sheng, H Yao
OBJECTIVE: To investigate the protective effects and underlying mechanisms of pachymic acid (PA) on sepsis-induced acute kidney injury (AKI). MATERIALS AND METHODS: Sepsis-induced AKI model was made by cecal ligation and puncture (CLP) surgery in SD rats. Animals were randomly divided into 5 groups: a sham group, a CLP group, and three PA-treated groups, which received intraperitoneal injection of PA at the dosage of 5, 20 and 50 mg/kg.bw, respectively. Kidney index, Cre and BUN contents were determined to evaluate the renal function...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28485323/rhubarb-monomers-protect-intestinal-mucosal-barrier-in-sepsis-via-junction-proteins
#18
Lyu Wang, Yun-Liang Cui, Zhe Zhang, Zhao-Fen Lin, De-Chang Chen
BACKGROUND: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. METHODS: Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0...
May 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28484719/glycyrrhizin-protects-rats-from-sepsis-by-blocking-hmgb1-signaling
#19
Feng Zhao, Yong Fang, Shuixiang Deng, Xiantao Li, Yun Zhou, Ye Gong, Hechen Zhu, Wei Wang
Background. HMGB1 acts as an important inflammatory mediator and is a potential therapeutic target for sepsis. Glycyrrhizin (GL), a natural triterpene glycoside derived from licorice, has been demonstrated to inhibit HMGB1 activity. The aim of this study is to explore how GL affects the HMGB1 signaling in sepsis. Methods. We used a CLP model of sepsis and in vitro LPS or HMGB1-treated NR8383 cells to examine the effects of GL on expression of HMGB1 and proinflammatory cytokines. Furthermore, we explored the effect of GL on interactions between HMGB1 and RAGE or TLR4 and the activations of NF-κB and MAPKs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28483456/protective-role-of-cgmp-in-early-sepsis
#20
Vanessa Kovalski, Ana P Prestes, Junior G Oliveira, Gustavo F Alves, Daiandra Fr Colarites, Jheniffer El Mattos, Regina Sordi, José Cr Vellosa, Daniel Fernandes
Septic shock, which is triggered by microbial products, is mainly characterised by inadequate tissue perfusion, which can lead to multiple organ dysfunction and death. An intense release of vasoconstrictors agents occurs in the early stages of shock, which can lead to ischemic injury. In this scenario, cGMP could play a key role in counterbalancing these agents and preventing tissue damage. Sildenafil, which is a phosphodiesterase-5 inhibitor, increases cGMP in smooth muscle cells and promotes vasodilation...
May 5, 2017: European Journal of Pharmacology
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