Sirolimus Attenuates Reduced-Size Liver Ischemia–Reperfusion Injury But Impairs Liver Regeneration in Rats

Liu, Yuan; Jin, Liming; Zhou, Lin; Xie, Haiyang; Jiang, Guoping; Chen, Hui; Zheng, Shusen

doi:10.1007/s10620-009-1002-2

Cited by 18 publications

(6 citation statements)

References 47 publications

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“…The I/R process leads to remarkable enhancement in the activities of these serum enzymes (Fig. 7d), proving that direct correlation between liver dysfunction and I/R process does exist, and the results are similar to literature reports 62,63 .…”

Section: Resultssupporting

confidence: 90%

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Chen

et al. 2021

Nat Commun

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Developing high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.

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Section: Resultssupporting

confidence: 90%

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Chen

et al. 2021

Nat Commun

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“…However, delayed liver regeneration has been reported in the initial phase after orthotopic liver transplantation [27–29]. Furthermore, several previously published studies have shown a significant decrease in proliferating hepatocytes after treatment with mTOR inhibitors, based on the function of the phosphoinositide 3-kinase (PI3K) signaling pathway on survival, autophagy, and proliferation [29–31]. Fouraschen et al showed that the mTOR inhibitor, rapamycin, regulated not only cell proliferation but also increased hepatic autophagy during liver regeneration [32].…”

Section: Discussionmentioning

confidence: 99%

Alloresponses of Mixed Lymphocyte Hepatocyte Culture to Immunosuppressive Drugs as an In-Vitro Model of Hepatocyte Transplantation

et al. 2019

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Background Hepatocyte transplantation (HCTx) has the potential for the treatment of end-stage liver disease. However, failure of engraftment and the long-term acceptance of cellular allografts remain significant challenges for its clinical application. The aim of this study was to investigate the efficacy of the immunosuppressive agents, Cyclosporine, Everolimus, and Belatacept to suppress the alloresponse of primary human hepatocytes in a mixed lymphocyte-hepatocyte culture (MLHC) and their potential hepatotoxicity in vitro . Material/Methods Primary human hepatocytes were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an MLHC. Proliferative alloresponses were determined by flow cytometry, and cytokine secretion was measured using Luminex-based multiplex technology. Using an MLHC, the alloresponses of primary human hepatocytes were compared in the presence and absence of Cyclosporine, Everolimus, and Belatacept. Cultured primary human hepatocytes were assessed for the production of albumin, urea, aspartate transaminase (AST) and DNA content. Metabolic activity was determined with the MTT assay. Results Immune responses induced by primary human hepatocytes were effectively suppressed by Cyclosporine, Everolimus, and Belatacept. Everolimus significantly reduced the metabolic activity of primary human hepatocytes in vitro , suggesting impairment of cell viability. However, further functional analysis showed no significant differences between treated and untreated controls. Conclusions Cyclosporine, Everolimus, and Belatacept suppressed the alloresponse of primary human hepatocytes in an MLHC without significant cytotoxicity or functional cell impairment.

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“…Reductions in MDA levels by the administration of rapamycin were detected in several studies. 28,29 Accordingly, it was shown that rapamycin reduced increased levels of NO in the rat brain. 29 Nevertheless, how rapamycin alleviates tissue insult in diabetic retinopathy remains tentative.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

Özdemir

Kılınç

Ergün

et al. 2014

Canadian Journal of Ophthalmology

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Sirolimus Attenuates Reduced-Size Liver Ischemia–Reperfusion Injury But Impairs Liver Regeneration in Rats

Abstract: Long term, BMDCs could repopulate recipient's intestinal epithelium even without any special treatment, which suggests a novel insight into the maintenance of the intestinal epithelial constitution.

Cited by 18 publications

References 47 publications

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Alloresponses of Mixed Lymphocyte Hepatocyte Culture to Immunosuppressive Drugs as an In-Vitro Model of Hepatocyte Transplantation

Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

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