scholarly journals Protective Role of an Initial Low-Dose Septic Challenge against Lethal Sepsis in Neonatal Mice: A Pilot Study

2021 ◽  
Vol 10 (24) ◽  
pp. 5823
Author(s):  
Ruka Nakasone ◽  
Mariko Ashina ◽  
Takumi Kido ◽  
Harunori Miyauchi ◽  
Masafumi Saito ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Lethal Dose ◽  
Protective Role ◽  
Bacterial Invasion ◽  
Initial Exposure ◽  
Lethal Sepsis

Neonatal sepsis is characterized by systemic bacterial invasion followed by a massive inflammatory response. At present, no therapeutic strategy has been found that significantly reduces the mortality of neonatal sepsis. We aimed to investigate the protective role of an initial low-dose septic challenge for the prevention of subsequent lethal sepsis in a mouse model. A stock cecal slurry (CS) solution was prepared from adult ceca. The LD83 (1.5 mg CS/g) was used for all animals. An initial challenge of normal saline (NS) or 0.5 mg CS/g (non-lethal dose) was administered at four days of age, then 1.5 mg CS/g was administered intraperitoneally at seven days of age (72 h post-initial challenge), and survival was monitored. Initial exposure to NS (n = 10) resulted in 90% mortality following exposure to the LD83 CS dose in contrast to an initial exposure to CS (n = 16), which significantly decreased mortality to 6% (p < 0.0001), reduced blood bacterial counts, attenuated inflammatory responses, and suppressed lipid mediators. Initial exposure to a non-lethal CS dose prior to exposure to a lethal CS dose significantly reduces sepsis mortality, a protective effect that might be mediated by modulating abnormal systemic inflammatory responses.

Protective role of low-dose TGF-β1 in early diabetic nephropathy induced by streptozotocin

2013 ◽  
Vol 17 (3) ◽  
pp. 752-758 ◽  
Author(s):  
Xiaodong Ma ◽  
Jingjing Ding ◽  
Haiyan Min ◽  
Yanting Wen ◽  
Qian Gao
Keyword(s):  
Diabetic Nephropathy ◽  
Low Dose ◽  
Protective Role ◽  
Early Diabetic Nephropathy ◽  
Tgf Β1

The protective role of alpha-lipoic acid on long-term exposure of rats to the combination of chlorpyrifos and deltamethrin pesticides

2016 ◽  
Vol 33 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Chidiebere Uchendu ◽  
Suleiman F Ambali ◽  
Joseph O Ayo ◽  
King AN Esievo
Keyword(s):  
Lipoic Acid ◽  
Lethal Dose ◽  
Liver Homogenate ◽  
Experimental Period ◽  
Protective Role ◽  
Serum Glucose ◽  
Group I ◽  
Male Wistar Rats

The study was aimed at evaluating the protective role of α-lipoic acid (ALA) on long-term exposure of rats to the combination of chlorpyrifos (CPF) and deltamethrin (DLT). Forty-two (42) male Wistar rats were divided into 6 exposure groups with 7 animals in each group: (I) soya oil (2 ml kg−1), (II) ALA (60 mg kg−1), (III) DLT (6.25 mg kg−1), (IV) CPF (4.75 mg kg−1), (V) (CPF + DLT) DLT (6.25 mg kg−1) and CPF (4.75 mg kg−1; 1/20th of the previously determined median lethal dose) and (VI) (ALA + CPF + DLT) pretreated with ALA (60 mg kg−1) and then co-exposed to CPF and DLT, 45 min later. The regimens were administered by gavage once daily for a period of 16 weeks. Sera obtained from blood collected at the end of the experimental period were used for the evaluation of serum glucose, total protein, albumin, urea, creatinine and the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and acetylcholinesterase. The liver homogenate was used to assay for the activities of superoxide dismutase and glutathione peroxidase and the concentrations of malondialdehyde, cytokine and tumour necrotic factor α. The result showed that the combination of CPF and DLT resulted in marked alterations of these biochemical parameters in most cases compared to either of the pesticides singly, supplementation with ALA ameliorated these alterations.

scholarly journals Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice

2020 ◽  
Vol 40 (9) ◽  
pp. 2070-2083
Author(s):  
Lin-Lin Wei ◽  
Ning Ma ◽  
Kun-Yi Wu ◽  
Jia-Xing Wang ◽  
Teng-Yue Diao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Protective Role ◽  
Plaque Burden ◽  
Aortic Tissue ◽  
M2 Macrophage ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Objective: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar −/− /Apoe −/− mice were generated by cross-breeding of atherosclerosis-prone Apoe −/− mice and C3ar −/− mice. C3ar −/− /Apoe −/− mice and Apoe −/− mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b + leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe −/− mice, C3ar −/− /Apoe −/− mice developed more severe atherosclerosis. In addition, C3ar −/− /Apoe −/− mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. Conclusions: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis–mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.

scholarly journals A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 589 ◽  
Author(s):  
Christoph F. A. Vogel ◽  
Yasuhiro Ishihara ◽  
Claire E. Campbell ◽  
Sarah Y. Kado ◽  
Aimy Nguyen-Chi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Responses ◽  
Environmental Pollutants ◽  
Protective Role ◽  
Potential Therapeutic Target ◽  
Embryonic Fibroblasts ◽  
Aryl Hydrocarbon ◽  
Enhancer Binding Protein

The aryl hydrocarbon receptor (AhR) is known for mediating the toxicity of environmental pollutants such as dioxins and numerous dioxin-like compounds, and is associated with the promotion of various malignancies, including lymphoma. The aryl hydrocarbon receptor repressor (AhRR), a ligand-independent, transcriptionally inactive AhR-like protein is known to repress AhR signaling through its ability to compete with the AhR for dimerization with the AhR nuclear translocator (ARNT). While AhRR effectively blocks AhR signaling, several aspects of the mechanism of AhRR’s functions are poorly understood, including suppression of inflammatory responses and its putative role as a tumor suppressor. In a transgenic mouse that overexpresses AhRR (AhRR Tg) we discovered that these mice suppress 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)- and inflammation-induced tumor growth after subcutaneous challenge of EL4 lymphoma cells. Using mouse embryonic fibroblasts (MEF) we found that AhRR overexpression suppresses the AhR-mediated anti-apoptotic response. The AhRR-mediated inhibition of apoptotic resistance was associated with a suppressed expression of interleukin (IL)-1β and cyclooxygenase (COX)-2, which was dependent on activation of protein kinase A (PKA) and the CAAT-enhancer-binding protein beta (C/EBPβ). These results provide mechanistic insights into the role of the AhRR to suppress inflammation and highlight the AhRR as a potential therapeutic target to suppress tumor growth.

scholarly journals The effect of low dose statin combined with grapefruit on muscle structure and the possible protective role of mesenchymal stem cells

QJM ◽  
2018 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
W Baher ◽  
A A Abo Zeid ◽  
B Mohamed Fahmy ◽  
A Mohamed Hashem ◽  
R Ashraf Sakr ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Low Dose ◽  
Protective Role ◽  
Muscle Structure

scholarly journals Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1β

2008 ◽  
Vol 294 (4) ◽  
pp. E709-E718 ◽  
Author(s):  
Klemen Strle ◽  
Robert H. McCusker ◽  
Rodney W. Johnson ◽  
Samantha M. Zunich ◽  
Robert Dantzer ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Muscle Wasting ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Protective Role ◽  
Igf I ◽  
Anti Inflammatory ◽  
Kinase Pathway ◽  
Anti Inflammatory Cytokine

Prolonged and excessive inflammation is implicated in resistance to the biological actions of IGF-I and contributes to the pathophysiology of neurodegenerative, metabolic, and muscle-wasting disorders. IL-10 is a critical anti-inflammatory cytokine that restrains inflammatory responses in macrophages and T cells by inhibiting cytokine and chemokine synthesis and reducing expression of their receptors. Here we demonstrate that IL-10 plays a protective role in nonhematopoietic cells by suppressing the ability of exogenous IL-1β to inhibit IGF-I-induced myogenin and myosin heavy chain expression in myoblasts. This action of IL-10 is not caused by impairment of IL-1β-induced synthesis of IL-6 or the ability of IL-1β to activate two members of the MAPK family, ERK1/2 and p38. Instead, this newly defined protective role of IL-10 occurs by specific reversal of IL-1β activation of the JNK kinase pathway. IL-10 blocks IL-1β-induced phosphorylation of JNK, but not ERK1/2 or p38, indicating that only the JNK component of the IL-1β-induced MAPK signaling pathway is targeted by IL-10. This conclusion is supported by the finding that a specific JNK inhibitor acts similarly to IL-10 to restore IGF-I-induced myogenin expression, which is suppressed by IL-1β. Collectively, these data demonstrate that IL-10 acts in a novel, nonclassical, protective manner in nonhematopoietic cells to inhibit the IL-1β receptor-induced JNK kinase pathway, resulting in prevention of IGF-I resistance.

Protective Role of Poria Cocos Polysaccharide Induced Differentiation of Bone Marrow Mesenchymal Stem Cells in Chronic Kidney Disease

2021 ◽  
Vol 20 (1) ◽  
pp. 177-184
Author(s):  
Yanping Fu ◽  
Daliang Yu ◽  
Xi Xie ◽  
Yu Huang ◽  
Shuhui Li
Keyword(s):  
Therapeutic Strategy ◽  
Protective Role ◽  
Poria Cocos ◽  
Traditional Chinese Herbal Medicine ◽  
Chinese Herbal ◽  
Renal Morphology ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Renal Regeneration

The progressive loss of renal function and accumulation of collagen leads to CKD. Human BM-MSCs are considered as an ideal therapeutic strategy for renal regeneration in the CKD. Polysaccharides extracted from Poria cocos, an edible medicinal mushroom, have been in use in the traditional Chinese herbal medicine as they exhibit antidiabetic, antioxidative, antitumor, and other pharmacological effects. Whether the polysaccharides of P. cocos could ameliorate the CKD via induction of BM-MSC differentiation remains to be explored. The data presented here show that the polysaccharides of P. cocos not only induced BM-MSC proliferation and differentiation, but also reduced the levels of proinflammatory cytokines and improved renal morphology.

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