scholarly journals Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury

Lab on a Chip ◽  
2014 ◽  
Vol 14 (16) ◽  
pp. 3081-3092 ◽  
Author(s):  
Mandy B. Esch ◽  
Gretchen J. Mahler ◽  
Tracy Stokol ◽  
Michael L. Shuler
Keyword(s):  
Gastrointestinal Tract ◽  
Liver Injury ◽  
Medical Applications ◽  
Human Tissues ◽  
Ingested Nanoparticles ◽  
Liver Tissues

The use of nanoparticles in medical applications is highly anticipated, and at the same time little is known about how these nanoparticles affect human tissues.

scholarly journals Simultaneous Inhibition of Three Major Cytokines and Its Therapeutic Effects: A Peptide-Based Novel Therapy against Endotoxemia in Mice

2021 ◽  
Vol 11 (5) ◽  
pp. 436
Author(s):  
Hung-Jen Shih ◽  
Chao-Yuan Chang ◽  
Milton Chiang ◽  
Van Long Le ◽  
Hao-Jen Hsu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Therapeutic Effects ◽  
The Novel ◽  
Tissue Water ◽  
Novel Therapy ◽  
Binding Domains ◽  
Tnf Α ◽  
Simultaneous Inhibition ◽  
Factor Α ◽  
Liver Tissues

Three major cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, mediate endotoxemia-induced liver injury. With the similar structures to the binding domains of the three cytokines to their cognate receptors, the novel peptide KCF18 can simultaneously inhibit TNF-α, IL-1β, and IL-6. We elucidated whether KCF18 can alleviate injury of liver in endotoxemic mice. Adult male mice (BALB/cJ) were intraperitoneally (i.p.) administered lipopolysaccharide (LPS, 15 mg/kg; LPS group) or LPS with KCF18 (LKCF group). Mice in the LKCF group received KCF18 (i.p.) at 2 h (0.6 mg/kg), 4 h (0.3 mg/kg), 6 h (0.3 mg/kg), and 8 h (0.3mg/kg) after LPS administration. Mice were sacrificed after receiving LPS for 24 h. Our results indicated that the binding levels of the three cytokines to their cognate receptors in liver tissues in the LKCF group were significantly lower than those in the LPS group (all p < 0.05). The liver injury level, as measured by performing functional and histological analyses and by determining the tissue water content and vascular permeability (all p < 0.05), was significantly lower in the LKCF group than in the LPS group. Similarly, the levels of inflammation (macrophage activation, cytokine upregulation, and leukocyte infiltration), oxidation, necroptosis, pyroptosis, and apoptosis (all p < 0.05) in liver tissues in the LKCF group were significantly lower than those in the LPS group. In conclusion, the KCF18 peptide–based simultaneous inhibition of TNF-α, IL-1β, and IL-6 can alleviate liver injury in mice with endotoxemia.

scholarly journals Ursodeoxycholic Acid (UDCA) Increases Lactate Clearance and Reduces Liver Injury by Inhibiting Farnesoid X Receptor (FXR) in Hemorrhagic Shock (HS)

2021 ◽  
Author(s):  
Lu Wang ◽  
Xi Rui ◽  
Huai-Wu He ◽  
Xiang Zhou ◽  
Yun Long
Keyword(s):  
Liver Injury ◽  
Hemorrhagic Shock ◽  
Ursodeoxycholic Acid ◽  
Adult Male ◽  
Acute Liver Injury ◽  
Lactate Concentration ◽  
Lactate Clearance ◽  
Farnesoid X Receptor ◽  
Lactate Levels ◽  
Liver Tissues

Abstract Background: Hemorrhagic shock (HS) is one of the leading causes of death worldwide. Acute liver injury (ALI) is an important manifestation of HS. Farnesoid X receptor (FXR) plays an important role in the liver protection of bile acids. Therefore, we designed this experiment to study the effect of ursodeoxycholic acid (UDCA) on acute liver injury and its relationship with the FXR pathway in HS.Methods: In this study, eighteen adult male C57BL/6 mice were randomly divided into 3 groups of six mice per group applying a table of random numbers: sham group; HS group and HS + UDCA group. Six FXR (-/-) adult male C57BL mice were classified as FXR (-/-) + HS + UDCA group. As to model of HS, MAP of 40 ± 5 mmHg was maintained for 1 hour. As to UDCA intervention, UDCA (300mg/kg) was given nasally fed. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) were quantified with chromatographic quantitative kits according to the manufacturer’s instructions. Lactate concentration was determined by an automatic biochemical analyzer. The liver tissues were stained with hematoxylin and eosin (H&E) and scored histopathologically.Results: Plasma ALT, AST and lactate levels decreased significantly after treatment with UDCA under HS conditions. Pathological scores of liver tissues decreased significantly after treatment with UDCA under HS conditions. In the case of FXR (-/-), the influence of UDCA was inhibited.Conclusions: UDCA can reduce ALT, AST and lactate levels and alleviate liver injury during HS through the FXR pathway.

The human archaeome: methodological pitfalls and knowledge gaps

2018 ◽  
Vol 2 (4) ◽  
pp. 469-482 ◽  
Author(s):  
Alexander Mahnert ◽  
Marcus Blohs ◽  
Manuela-Raluca Pausan ◽  
Christine Moissl-Eichinger
Keyword(s):  
Multiple Sclerosis ◽  
Gastrointestinal Tract ◽  
Methanogenic Archaea ◽  
Human Tissues ◽  
Health Issues ◽  
Human Gastrointestinal Tract ◽  
Knowledge Gaps ◽  
Site Specific ◽  
Long Time ◽  
Methodological Problems

Forty years ago, archaea were described as a separate domain of life, distinct from bacteria and eukarya. Although it is known for quite a long time that methanogenic archaea are substantial components of the human gastrointestinal tract (GIT) and the oral cavity, the knowledge on the human archaeome is very limited. Various methodological problems contribute to the invisibility of the human archaeome, resulting in severe knowledge gaps and contradictory information. Similar to the bacteriome, the archaeal biogeography was found to be site-specific, forming (i) the thaumarchaeal skin landscape, (ii) the (methano)euryarchaeal GIT landscape, (iii) a mixed skin/GIT landscape in nose, and (iv) a woesearchaeal lung landscape, including numerous unknown archaeal clades. Compared with so-called universal microbiome approaches, archaea-specific protocols reveal a wide diversity and high quantity of archaeal signatures in various human tissues, with up to 1 : 1 ratios of bacteria and archaea in appendix and nose samples. The archaeome interacts closely with the bacteriome and the human body cells, whereas the roles of the human-associated archaea with respect to human health are only sparsely described. Methanogenic archaea and methane production were correlated with many health issues, including constipation, periodontitis and multiple sclerosis. However, one of the most burning questions — do archaeal pathogens exist? — still remains obscure to date.

scholarly journals Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
De-Long Kong ◽  
Fan-Yun Kong ◽  
Xiang-Ye Liu ◽  
Chao Yan ◽  
Jie Cui ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Injury ◽  
Schistosoma Japonicum ◽  
Hepatic Stellate Cells ◽  
Flow Cytometric Analysis ◽  
Stellate Cells ◽  
Ros Generation ◽  
Caspase 1 ◽  
Egg Antigen ◽  
Liver Tissues

Abstract Background Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous studies have shown that caspase-1-mediated pyroptosis participates in the development of multiple inflammation-related diseases. However, whether pyroptotic cell death of HSCs is involved in SEA-mediated liver damage is not well understood. Methods Primary cultured HSCs and Schistosoma japonicum-infected mouse liver tissue were analysed for histological changes and caspase-1 activation, and the role of pyroptosis in the mechanisms underlying SEA-induced HSC death was investigated. Accumulation of reactive oxygen species (ROS) in infected livers and SEA-stimulated HSCs was measured by flow cytometry and immunofluorescence. Results Caspase-1 activity was elevated in both liver tissues and HSCs of S. japonicum-infected mice. Furthermore, SEA stimulation increased the proportion of pyroptotic HSCs, as shown by lactate dehydrogenase (LDH) release assays and by flow cytometric analysis of propidium iodide (PI) and caspase-1 double staining in cells. In addition, ROS generation was elevated in infected liver tissues and SEA-stimulated HSCs, and ROS inhibition downregulated SEA-induced caspase-1 activation and pyroptosis in HSCs. Conclusions Our present study demonstrates that pyroptotic cell death in HSCs induced by SEA via ROS-mediated caspase-1 activation may serve as a significant mechanism to initiate the inflammatory response and thereby exacerbate liver injury during S. japonicum infection.

Protective role of Salvia miltiorrhiza Polysaccharides on Florfenicol Induced Oxidative and Apoptotic Injury of Liver in Broilers

2021 ◽  
Author(s):  
Xiao Wang ◽  
Yuqing Cui ◽  
Chao Han ◽  
Yumeng Geng ◽  
Di Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Protein Expression ◽  
Liver Tissue ◽  
Salvia Miltiorrhiza ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mrna And Protein Expression ◽  
Liver Tissues

Abstract Salvia miltiorrhiza Polysaccharides (SMPs) can alleviate liver injury in mice, but there are few reports on liver injury of broilers, especially the liver injury caused by antibiotics. To explore the hepatoprotective effects of SMPs against florfenicol (FFC) induced broilers liver injury, the broilers were treated with FFC and SMPs. The results showed SMPs could significantly inhibit the decrease of weight gain and the increase of liver index induced by FFC (P < 0.05). SMPs could significantly reduce the contents of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) in serum and the malondialdehyde (MDA), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in liver tissues (P < 0.05), also significantly increased the content of total protein (TP) in serum and superoxide dismutase (SOD), catalase (CAT) in liver tissues (P < 0.05). QPCR and western bolt results showed that SMPs significantly increased the mRNA and protein expression of cytochrome P4501A1 (CYP1A1), cytochrome P4502H1 (CYP2H1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in liver tissue, also significantly reduced the rate of hepatocyte apoptosis and the mRNA and protein expression of p53, cytochrome-C (CytC), caspase-3 in liver tissue (P < 0.05). The results demonstrated that SMPs can inhibit the oxidative stress in hepatocytes by regulating the related proteins in Nrf2 pathway, thereby reducing the apoptosis of hepatocytes, and protecting liver injury.

The Liver

Bioprinting ◽  
2021 ◽  
pp. 119-137
Author(s):  
Kenneth Douglas
Keyword(s):  
Liver Injury ◽  
Blood Supply ◽  
Liver Tissue ◽  
Liver Cells ◽  
Human Hepatocytes ◽  
Human Tissues ◽  
Vital Functions ◽  
Regenerative Ability ◽  
Hybrid Printing

Abstract: This chapter reports on efforts to bioprint liver tissue, including the important types of liver cells and also the liver’s cytoarchitecture—the typical pattern of cellular arrangement within liver tissue. The chapter gives an account of the liver’s remarkable regenerative ability, its over 500 vital functions, its unusual blood supply, and the difficulty of growing liver cells in vitro (in the laboratory). The chapter includes a description of a hybrid printing/casting method employing human hepatocytes (liver cells) encapsulated in a hydrogel called a “liver tissue seed.” Implanted into mice with a liver injury, the seed tissue provided functional support to the failing liver and expanded in size by 50-fold over the course of 11 weeks. The chapter also mentions Organovo, the first commercial bioprinting company and a pioneer in bioprinting commercially available human tissues, notably their lead product, liver tissue.

scholarly journals Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro

2016 ◽  
Vol 40 (1-2) ◽  
pp. 49-61 ◽  
Author(s):  
Quanfang Huang ◽  
Chunhong Liang ◽  
Ling Wei ◽  
Jinlan Nie ◽  
Shengjuan Lu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Inhibitory Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitory Protein ◽  
Liver Tissues

Background/Aims: Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. Methods: In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. Results: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. Conclusion: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.

scholarly journals Immunohistochemical Localization of Fibrinogen C Domain Containing 1 on Epithelial and Mucosal Surfaces in Human Tissues

2017 ◽  
Vol 66 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Sebastian von Huth ◽  
Jesper B. Moeller ◽  
Anders Schlosser ◽  
Niels Marcussen ◽  
Ole Nielsen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Epithelial Cells ◽  
Immunohistochemical Localization ◽  
Human Tissues ◽  
Sebaceous Glands ◽  
Binding Properties ◽  
High Affinity ◽  
Mucosal Surfaces ◽  
Columnar Cells ◽  
Small And Large Intestine

Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane receptor that binds chitin and other acetylated compounds with high affinity. FIBCD1 has previously been shown to be present in the epithelium of the gastrointestinal tract. In the present study, we performed a detailed analysis of normally structured human tissues for the expression of FIBCD1 by quantitative PCR and immunohistochemistry. We find that FIBCD1 is expressed in epithelial cells derived from all three germ layers. Endodermal-derived epithelial cells throughout the gastrointestinal tract and the respiratory system showed high expression of FIBCD1 and also mesodermal-derived cells in the genitourinary system and ectodermal-derived epidermis and sebaceous glands cells expressed FIBCD1. In some columnar epithelial cells, for example, in the salivary gland and gall bladder, the FIBCD1 expression was clearly polarized with strong apical reaction, while other columnar cells, for example, in small and large intestine and in bronchi, the staining was equally strong apically and basolaterally. In keratinocytes in skin, tongue, and oral cavity, the FIBCD1 staining was granular. This expression pattern together with the known binding properties supports that FIBCD1 plays a role in innate immunity in the skin and at mucosal surfaces.

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