High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of thePI3K/Akt1 pathway

Chen, Ouyang; Cao, Zhiyong; Li, He; Ye, Zhouheng; Zhang, Rongjia; Zhang, Ning; Huang, Jun; Zhang, Ting; Wang, Liping; Han, Ling; Liu, Wenwu; Sun, Xuejun

doi:10.1038/s41598-017-14072-x

Cited by 24 publications

(18 citation statements)

References 38 publications

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“…The recent development of the H 2 generator has led to a gradual increase in the number of studies using high concentrations of H 2 . Inhalation of high concentrations of H 2 has been proved to ameliorate ischemia/reperfusion injury ( 36 , 37 ), endometriosis ( 38 ) and glyoxylate-induced calcium oxalate deposition ( 39 ) in animal models. Commercially available machines for inhalation of high concentrations of H 2 have also been used in patients ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats

Liu¹,

Xue²,

Zhang³

et al. 2020

Mol Med Rep

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Hydrogen exhibits therapeutic and preventive effects against various diseases. The present study investigated the potential protective effect and dose-dependent manner of hydrogen inhalation on high fat and fructose diet (HFFd)-induced nonalcoholic fatty liver disease (naFld) in Sprague-dawley rats. rats were randomly divided into four groups: i) control group, regular diet/air inhalation; ii) model group, HFFd/air inhalation; iii) low hydrogen group, HFFd/4% hydrogen inhalation; and iv) high hydrogen group, HFFd/67% hydrogen inhalation. after a 10-week experiment, hydrogen inhalation ameliorated weight gain, abdominal fat index, liver index and body mass index of rats fed with HFFd and lowered the total area under the curve in an oral glucose tolerance test. Hydrogen inhalation also ameliorated the increase in liver lipid content and alanine transaminase and aspartate transaminase activities. liver histopathologic changes evaluated with hematoxylin and eosin as well as oil red o staining revealed lower lipid deposition in hydrogen inhalation groups, consistent with the decrease in the expression of the lipid synthesis gene SREBP-1c. The majority of the indicators were affected following treatment with hydrogen in a dose-dependent manner. in conclusion, hydrogen inhalation may play a protective role by influencing the general state, lipid metabolism parameters, liver histology and liver function indicators in the rat model of metabolic syndrome with naFld.

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Section: Discussionmentioning

confidence: 99%

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats

Liu¹,

Xue²,

Zhang³

et al. 2020

Mol Med Rep

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show abstract

“…To confirm the important role of AKT/GSK-3β in the treatment of PHLF by MSCs, we used an AKT inhibitor to activate GSK-3β by suppressing the phosphorylation of GSK-3β (Chen et al, 2017). We found that when GSK-3β was activated, the therapeutic effect of MSCs was eliminated.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Improve Glycometabolism and Liver Regeneration in the Treatment of Post-hepatectomy Liver Failure

et al. 2019

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Background The mortality rate of post-hepatectomy liver failure (PHLF) remains very high, and liver transplantation is the only effective treatment regimen for PHLF. Cell transplantation is a potential treatment for liver diseases. Previous studies have proved that mesenchymal stem cells (MSCs) have immunomodulatory functions. In the present study, we found that MSCs promoted glycogen synthesis and liver regeneration in the treatment of PHLF. MSC transplantation also improved the survival rate of rats after 90% partial hepatectomy (PH). In our current study, we aimed to determine the efficacy and mechanism of MSC transplantation in the treatment of PHLF. Methods Mesenchymal stem cells were isolated from Sprague-Dawley rats and cultured using a standardized protocol. The MSCs were transplanted to treat acute liver failure induced by 90% PH. The therapeutic efficacy of MSCs on PHLF was verified through measuring alanine transaminase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), serum ammonia, liver weight to body weight ratio, blood glucose, and histology. To further study the mechanism of MSC transplantation in treatment for PHLF, we assessed the changes in the AKT/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway. A-674563 (AKT inhibitor) and SB216763 (GSK-3β inhibitor) were employed to validate our findings. SPSS version 19.0 was used for statistical analysis, and the independent-samples t -test was carried out to analyze the collected data. Results Mesenchymal stem cell transplantation attenuated the liver injury in acute liver failure induced by 90% PH. MSC transplantation improved the glucose metabolism and survival rate in the PHLF model. The effect of MSC transplantation on hepatocyte proliferation might be related to AKT/GSK-3β/β-catenin pathway. Conclusion Mesenchymal stem cell transplantation could be use as a potential treatment for PHLF.

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“…The therapeutic agents, including paclitaxel, cisplatin, bevacizumab, and olaparib (all from Sigma-Aldrich), diluted with DMSO, was intraperitoneally administered to mice. Anti-BTLA Ab (clone 6A6, Bio X cell) [28], anti-PD-1 Ab (clone RMP1–14, Bio X cell) [29], anti-PD-L1 Ab (clone 10F.9G2, Bio X cell) [30], anti-CD19 Ab (clone 1D3, Bio X cell) [31], LY294002 (Selleck Chemicals) [32], and BP-1-102 (Selleck Chemicals) [33] were also used for the following experiments.…”

Section: Methodsmentioning

confidence: 99%

BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19high B lymphocytes

Chen

Lin

Chien

et al. 2019

j. immunotherapy cancer

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BackgroundThe standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC.MethodsInitially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases.ResultsThe combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19hi B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA+CD19hi B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients.ConclusionsBTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients.Trial registrationThe Trial Registration Number was NCT00854399.

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High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of thePI3K/Akt1 pathway

Cited by 24 publications

References 38 publications

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats

Mesenchymal Stem Cells Improve Glycometabolism and Liver Regeneration in the Treatment of Post-hepatectomy Liver Failure

BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19high B lymphocytes

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