Advances in sepsis-associated liver dysfunction

Wang, Dawei; Yin, Yimei; Yao, Yong‐Ming

doi:10.4103/2321-3868.132689

Cited by 99 publications

(55 citation statements)

References 63 publications

(64 reference statements)

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“…Similar pathological developments are observed in acute hepatic encephalopathy (AHE) resulting from liver failure, which frequently complicates sepsis [94,95]. In AHE excessive plasma-borne ammonium crosses often compromised BBB; ammonium is subsequently converted to glutamine by astrocytic glutamine synthetase, which is the key component of glutamate/GABA-glutamine cycle.…”

Section: Neurobiology Of Septic Encephalopathymentioning

confidence: 81%

Astroglia in Sepsis Associated Encephalopathy

Shulyatnikova

Verkhratsky

2019

Neurochem Res

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Cellular pathophysiology of sepsis associated encephalopathy (SAE) remains poorly characterised. Brain pathology in SAE, which is manifested by impaired perception, consciousness and cognition, results from multifactorial events, including high levels of systemic cytokines, microbial components and endotoxins, which all damage the brain barriers, instigate neuroinflammation and cause homeostatic failure. Astrocytes, being the principal homeostatic cells of the central nervous system contribute to the brain defence against infection. Forming multifunctional anatomical barriers, astroglial cells maintain brain-systemic interfaces and restrict the damage to the nervous tissue. Astrocytes detect, produce and integrate inflammatory signals between immune cells and cells of brain parenchyma, thus regulating brain immune response. In SAE astrocytes are present in both reactive and astrogliopathic states; balance between these states define evolution of pathology and neurological outcomes. In humans pathophysiology of SAE is complicated by frequent presence of comorbidities, as well as age-related remodelling of the brain tissue with senescence of astroglia; these confounding factors further impact upon SAE progression and neurological deficits.

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Section: Neurobiology Of Septic Encephalopathymentioning

confidence: 81%

Astroglia in Sepsis Associated Encephalopathy

Shulyatnikova

Verkhratsky

2019

Neurochem Res

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“…To create a second-degree thermal burn injury, a scalding apparatus was applied using a permanent temperature and pressure (YSL-5Q). A stainless steel cylinder with an area of 2 cm 2 was heated to 80 °C and placed on the shaved dorsal skin for 3 seconds at a pressure of 500 g [26]. Two wounds were produced on every mouse, and eight mice were included in each group.…”

Section: Methodsmentioning

confidence: 99%

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

Yao

Wang

et al. 2016

Stem Cell Res Ther

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BackgroundEpithelial to mesenchymal transition, especially to myofibroblasts, plays an important role in wound healing, fibrosis, and carcinogenesis. Epidermal stem cells (EpSCs) are responsible for epidermal renewal and wound re-epithelialization. However, it remains unclear whether and how EpSCs transdifferentiate into myofibroblasts or myofibroblast-like cells (MFLCs). Here, we provide the first evidence showing that P311 induces EpSC to MFLC transdifferentiation (EpMyT) via TGFβ1/Smad signaling.MethodsWound healing and mesenchymal features were observed in the P311 KO and P311 WT mouse model of superficial second-degree burns. After the primary human or mouse EpSCs were forced to highly express P311 using an adenoviral vector, EpMyT was observed by immunofluorescence, real-time PCR, and western blot. The activity of TGFβ1 and Smad2/3 in EpSCs with different P311 levels was observed by western blot. The TβRI/II inhibitor LY2109761 and Smad3 siRNA were applied to block the EpMyT in P311-overexpressing EpSCs and exogenous TGFβ1 was to restore the EpMyT in P311 KO EpSCs. Furthermore, the mechanism of P311 regulating TGFβ1 was investigated by bisulfite sequencing PCR, luciferase activity assay, and real-time PCR.ResultsP311 KO mouse wounds showed delayed re-epithelialization and reduced mesenchymal features. The human or mouse EpSCs with overexpressed P311 exhibited fusiform morphological changes, upregulated expression of myofibroblast markers (α-SMA and vimentin), and downregulated expression of EpSC markers (β1-integrin and E-cadherin). P311-expressing EpSCs showed decreased TGFβ1 mRNA and increased TGFβ1 protein, TβRI/II mRNA, and activated Smad2/3. Moreover, LY2109761 and Smad3 siRNA reversed P311-induced EpMyT. Under the stimulation of exogenous TGFβ1, the phosphorylation of Smad2 and Smad3 in P311 KO EpSCs was significantly lower than that in P311 WT EpSCs and the EpMyT in P311 KO EpSCs was restored. Furthermore, P311 enhanced the methylation of TGFβ1 promoter and increased activities of TGFβ1 5′/3′ untranslated regions (UTRs) to stimulate TGFβ1 expression. P311+α-SMA+ cells and P311+vimentin+ cells were observed in the epidermis of human burn wounds. Also, P311 was upregulated by IL-1β, IL-6, TNFα, and hypoxia.ConclusionsP311 is a novel TGFβ1/Smad signaling-mediated regulator of transdifferentiation in EpSCs during cutaneous wound healing. Furthermore, P311 might stimulate TGFβ1 expression by promoting TGFβ1 promoter methylation and by activating the TGFβ1 5′/3′ UTR.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0421-1) contains supplementary material, which is available to authorized users.

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“…6 mm sterile biopsy punches were used to create bilateral fullthickness wounds on the dorsum of the mice, and silicon splints (inner diameter = 6 mm, outer diameter = 9 mm, thickness = 1 mm) were then sutured on top of each wound. [60] The animals were assigned randomly to two endpoints and four groups for analysis: i) DPBS control (DPBS), ii) pure GelMA hydrogels (GelMA), iii) GelMA/NP negative miRNA control (Neg miRNA) and iv) GelMA/NP miR-233* (5.0%(w/w) NPs to GelMA concentration). For animals receiving the DPBS control, 50 µL of sterile DPBS was pipetted on top of each wound.…”

Section: Wwwsmall-journalcommentioning

confidence: 99%

Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA‐Laden Nanoparticles Promotes Wound Healing

Saleh

Dhaliwal

Portillo‐Lara

et al. 2019

Small

235

179

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Chronic wounds are characterized by impaired healing and uncontrolled inflammation, which compromise the protective role of the immune system and may lead to bacterial infection. Upregulation of miR‐223 microRNAs (miRNAs) shows driving of the polarization of macrophages toward the anti‐inflammatory (M2) phenotype, which could aid in the acceleration of wound healing. However, local‐targeted delivery of microRNAs is still challenging, due to their low stability. Here, adhesive hydrogels containing miR‐223 5p mimic (miR‐223*) loaded hyaluronic acid nanoparticles are developed to control tissue macrophages polarization during wound healing processes. In vitro upregulation of miR‐223* in J774A.1 macrophages demonstrates increased expression of the anti‐inflammatory gene Arg‐1 and a decrease in proinflammatory markers, including TNF‐α, IL‐1β, and IL‐6. The therapeutic potential of miR‐223* loaded adhesive hydrogels is also evaluated in vivo. The adhesive hydrogels could adhere to and cover the wounds during the healing process in an acute excisional wound model. Histological evaluation and quantitative polymerase chain reaction (qPCR) analysis show that local delivery of miR‐223* efficiently promotes the formation of uniform vascularized skin at the wound site, which is mainly due to the polarization of macrophages to the M2 phenotype. Overall, this study demonstrates the potential of nanoparticle‐laden hydrogels conveying miRNA‐223* to accelerate wound healing.

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Advances in sepsis-associated liver dysfunction

Cited by 99 publications

References 63 publications

Astroglia in Sepsis Associated Encephalopathy

Astroglia in Sepsis Associated Encephalopathy

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression

Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA‐Laden Nanoparticles Promotes Wound Healing

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