Grape Peel Extract and Resveratrol Inhibit Wrinkle Formation in Mice Model Through Activation of Nrf2/HO‐1 Signaling Pathway

Prokineticins are highly conserved small peptides family expressed in all vertebrates, which contain a wide spectrum of functions. In this study, a prokineticin homolog (Bv8-AJ) isolated from the venom of frog Amolops jingdongensis was fully characterized. Bv8-AJ accelerated full-thickness wounds healing of mice model by promoting the initiation and the termination of inflammatory phase. Moreover, Bv8-AJ exerted strong proliferative effect on fibroblasts and keratinocytes isolated from newborn mice by activating interleukin (IL)-1 production. Our findings indicate that Bv8 is a potent wound healing regulator and may reveal the mechanism of rapid wound-healing in amphibian skins.

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DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury

Cell Death Discovery ◽

10.1038/s41420-021-00528-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yinwu Bao ◽

Mengqiu Bai ◽

Huanhuan Zhu ◽

Yuan Yuan ◽

Ying Wang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Cell Injury ◽

Inflammatory Responses ◽

Kidney Injury ◽

Renal Tissue ◽

Clinical Samples ◽

Mice Model ◽

Expression Levels ◽

Ppar Signaling

AbstractDemethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

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YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia

Frontiers in Pediatrics ◽

10.3389/fped.2020.618226 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chao Zheng ◽

Jiaqian Luo ◽

Yifan Yang ◽

Rui Dong ◽

Fa-Xing Yu ◽

...

Keyword(s):

Bile Duct ◽

Liver Fibrosis ◽

Mouse Model ◽

Biliary Atresia ◽

Signaling Pathway ◽

Target Genes ◽

Hippo Signaling ◽

Mice Model ◽

Hippo Signaling Pathway ◽

Ductal Cells

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.

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Methionine Restriction Alleviates Aging-related Cognitive Dysfunction via Stimulating FGF21-driven Mitochondrial Biogenesis (P14-026-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz052.p14-026-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Bo Ren ◽

Luanfeng Wang ◽

Zhigang Liu ◽

Xuebo Liu

Keyword(s):

Amino Acid ◽

Cognitive Function ◽

Signaling Pathway ◽

Mitochondrial Biogenesis ◽

Metabolic Phenotype ◽

Fibroblast Growth Factor 21 ◽

Behavioral Tests ◽

Mice Model ◽

Neuroprotective Effects ◽

Methionine Restriction

Abstract Objectives Moderate dietary methionine restriction (MR) extends life span in various animal models and delays the onset of aging-associated pathologies. However, the neuroprotective effects and underlying mechanism of MR on age and age-related diseases still remain to be investigated. Notably, fibroblast growth factor-21 (FGF21), a MR responding hormone mostly generated from liver, plays a critical role in neuronal mitochondrial function. Here, we aimed to reveal the neuroprotective effects of MR and the mediating role of FGF21 in aging mice model. Methods Male C57BL/6 mice (2-, 12-, and 15- month-old) were treated with control methionine diet (0.86% methionine) and methionine restriction diet (0.17% methionine) for 3 months. Adeno-associated virus was employed to build FGF21 knockdown mice model. Behavioral tests, synapse ultrastructure detection, and amino acid metabolomics were performed to evaluate cognitive function, neuron damage and signaling pathway activation. Results In behavioral tests, we found that MR significantly improved aging-induced decreased in spatial memory and cognitive function. Meanwhile, MR ameliorated neuronal damage and synapses structure damages in aging mice hippocampus. Moreover, MR significantly improved the mRNA expression of mitochondrial biogenesis and dynamics related genes such as COX2/fis1/pink1/binp1/drp1 in aging mice brain. MR also altered plasma amino acid metabolic phenotype-related glutathione synthesis, energy metabolism, and nervous system function. Furthermore, we found that MR could significant increase FGF21 level in both liver and serum of aging mice. Knockdown of FGF21 dramatically diminished the benefits of MR on cognitive impairments. Conclusions These results showed that MR mitigated aging-induced memory impairment and synapses structure damages via activating FGF21 signaling pathway. The study suggest that this dietary restriction might be plausible therapeutic intervention for aging and other neurodegenerative diseases such AD and PD. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China. Supporting Tables, Images and/or Graphs

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Curcumin improves age-related and surgically induced osteoarthritis by promoting autophagy in mice

Bioscience Reports ◽

10.1042/bsr20171691 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 13

Author(s):

Guowang Zhang ◽

Jiaqing Cao ◽

Erzhu Yang ◽

Bo Liang ◽

Jianing Ding ◽

...

Keyword(s):

Signaling Pathway ◽

B Cell Lymphoma ◽

In Vivo Studies ◽

Terminal Deoxynucleotidyl Transferase ◽

Mice Model ◽

Curcumin Treatment ◽

Chondrocyte Death ◽

Age Related ◽

Surgically Induced

Reduced autophagy has been implied in chondrocyte death and osteoarthritis. Curcumin (Cur) owns therapeutic effect against osteoarthritis (OA) and enhances autophagy in various tumor cells. Whether the cartilage protection of curcumin is associated with autophagy promotion and the potential signaling pathway involved remains unclear. The present study aimed to investigate the role of autophagy in the anti-OA activity of curcumin using spontaneous and surgically induced OA mice model. Spontaneous and surgically induced OA mice model was established and treated with Cur. Articular cartilage destruction and proteoglycan loss were scored through Safranin O/Fast green staining. Apoptotic cell death was detected with TUNEL (terminal deoxynucleotidyl transferase-mediated dTUP-biotin nick end labeling assay) staining and Western blot for caspase-3, Bcl-2 associated X protein (Bax), and Bcl-2 (B-cell lymphoma-2). Light chain 3 (LC3) immunohistochemistry was used to evaluate autophagy. In vitro, primary chondrocytes were treated with interleukin 1 beta (IL-1β) and Cur. Autophagy was inhibited using 3-methyladenine. Apoptosis and autophagy were detected using flow cytometry and Western blotting assay. Curcumin treatment enhanced autophagy, reduced apoptosis, and cartilage loss in both OA models. In vitro, curcumin treatment improved IL-1β induced autophagy inhibition, cell viability decrease, and apoptosis. Mechanistically, in vivo studies suggested curcumin promoted autophagy through regulating Akt/mTOR pathway. In conclusion, our results demonstrate that curcumin-induced autophagy via Akt/mTOR signaling pathway contributes to the anti-OA effect of curcumin.

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Long non-coding RNA HAL suppresses the migration and invasion of serous ovarian cancer by inhibiting EMT signaling pathway

Bioscience Reports ◽

10.1042/bsr20194496 ◽

2020 ◽

Vol 40 (3) ◽

Cited By ~ 1

Author(s):

Ke Wu ◽

Lei Li ◽

Lin Li ◽

Dong Wang

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Migration And Invasion ◽

Serous Ovarian Cancer ◽

Mice Model ◽

Protein Levels ◽

Non Coding Rna ◽

Skov3 Cells ◽

Long Non Coding Rna

Abstract Objective: To investigate the specific function of long non-coding RNA HAL in serous ovarian cancer (SOC) and to further clarify the regulation of HAL on EMT pathway. Materials and methods: The expression of HAL and TWIST1 was detected by qRT-PCR. CCK8 assay, wound healing assay, transwell assay and flow cytometry were used to detect the HAL function on proliferation, migration, invasion and apoptosis in SOC cells. Western blot was used to calculate protein level of Vimentin, N-cadherin and E-cadherin. The effect of HAL on tumorigenesis of SOC was confirmed by xenograft nude mice model. Results: HAL was significantly decreased in SOC tissues and cells. Overexpression of HAL inhibited the proliferation, migration and invasion of SKOV3 cells, but promoted apoptosis. Furthermore, overexpression of HAL decreased the mRNA and protein levels of TWIST1 via a binding between HAL and TWIST1. Forced expression of TWIST1 reversed the inhibitory role of HAL on SOC cells’ migration and invasion. The in vivo tumor growth assay showed that HAL suppressed SOC tumorigenesis with inhibiting EMT pathway. Conclusions: Our research emphasized HAL acting as a tumor-inhibiting gene by regulating EMT signaling pathway, thus providing some novel experimental basis for clinical treatment of SOC.

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Constipation in Tg2576 mice model for Alzheimer’s disease associated with dysregulation of mechanism involving the mAChR signaling pathway and ER stress response

PLoS ONE ◽

10.1371/journal.pone.0215205 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0215205 ◽

Cited By ~ 2

Author(s):

Ji Eun Kim ◽

Jin Ju Park ◽

Mi Rim Lee ◽

Jun Young Choi ◽

Bo Ram Song ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Stress Response ◽

Er Stress ◽

Signaling Pathway ◽

Mice Model ◽

Er Stress Response ◽

Tg2576 Mice

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Overexpression of immune-responsive gene 1 prevents acute otitis media due to streptococcus pneumoniae infection through Nrf2- Hmox1 pathway

10.21203/rs.2.19489/v1 ◽

2019 ◽

Author(s):

Peizhen Yang ◽

Yufen Li ◽

Dongqing Wang ◽

Zhipeng Chen

Keyword(s):

Streptococcus Pneumoniae ◽

Inflammatory Response ◽

Signaling Pathway ◽

Otitis Media ◽

Middle Ear ◽

Acute Otitis Media ◽

Lavage Fluid ◽

Mice Model ◽

Nrf2 Signaling Pathway ◽

Positive Rate

Abstract Background: Acute otitis media (AOM) is one of the most commonly diagnosed childhood diseases that are associated with influenza infection. Immunoresponsive gene 1 (Irg1) is overexpressed in mammalian macrophage during inflammation process. Here, the present study aims to investigate the role of Irg1 in streptococcus pneumoniae infection-induced inflammatory response in AOM through Nrf2 signaling pathway. Methods: Positive rate of streptococcus pneumoniae and expression of Irg1, Nrf2 and Hmox1 were determined in the middle ear lavage fluid from 85 AOM patients infected with streptococcus pneumoniae and 48 healthy subjects. After the successful establishment of mice model with AOM, macrophage was harvest from the middle ear lavage fluid of mice. At last, to investigate the effect of Irg1 and Nrf2 signaling pathway on inflammatory response and streptococcus pneumoniae infection by accumulating macrophage, Irg1, sh-Irg1 and retinoic acid (an inhibitor of Nrf2 signaling pathway) were injected into AOM mice. Results: Irg1 exhibited a high level and activated Nrf2 signaling pathway was detected in AOM. Besides, positive rate of streptococcus pneumoniae was increased in AOM. Furthermore, in the mice model with AOM, Irg1 could repress inflammatory response by downregulating expression of TNF-α, IL-6 and IL-1β and inhibit streptococcus pneumoniae infection by stimulating accumulation of macrophage to increase its endocytosis through activation of Nrf2 signaling pathway. Conclusion: Taken together, Irg1 contributes to inhibiting inflammatory response and streptococcus pneumoniae infection in AOM by promoting accumulation of macrophage through activation of Nrf2 signaling pathway, which provides novel therapeutic targets for AOM therapy.

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The Deficiency of Maged1 Attenuates Parkinson's Disease Progression by Inhibiting Apoptosis and Enhancing Autophagy in Mice

10.21203/rs.3.rs-92068/v1 ◽

2020 ◽

Author(s):

Jie Wang ◽

Wei-Yan You ◽

Qing Ye ◽

Jia-Qi Zhang ◽

Chuan He ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Signaling Pathway ◽

Knockout Mice ◽

Gene Transfection ◽

Motor Deficits ◽

Mice Model

Abstract Background: Melanoma-associated antigen D1 (Maged1) is expressed in most adult tissues, predominantly in the brain, and has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, circadian rhythm, and drug addiction. However, the role of Maged1 in Parkinson’s disease (PD) remains unclear.Methods: Immunostaining was performed to investigate the expression of Maged1 in the samples from mice and human. To make the acute mice model of PD, C57BL/6 mice and Maged1 knockout mice were injected with 20 mg/kg 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) four times, every 2-hour intervals. SY5Y cells were treated by 200 μM 1-Methyl-4-phenylpyridinium iodide (MPP+). To examine motor balance and coordination, the rotarod test and pole test were used. Then we further investigated the role of Maged1 deficiency in DA neurons by high-performance liquid chromatography, immunohistochemistry, western blot, CCK8 assay, and gene transfection in vivo or in vitro.Results: Maged1 was expressed in DA neurons of samples from mice and human. And the expression of Maged1 was time-dependently upregulated by the treatment with MPTP or MPP+ in vivo or in vitro. Knockout of Maged1 in mice partly rescued the motor deficits and the reduced levels of striatal dopamine and its metabolites by MPTP treatment. Moreover, Maged1 deficiency protected primary DA neurons and differentiated ReNcell VM cells from MPP+ toxicity. Furthermore, along with the overexpression or downregulation of Maged1 in cultured SH-SY5Y cells, the reduced the cell viability by MPP+ treatment was relatively aggerated or attenuated. The effect of Maged1 deficiency may be attributed to the upregulated Akt signaling pathway and the downregulated mTOR signaling pathway, which further attenuated the MPTP or MPP+ -induced cell apoptosis and impairment of autophagy. Consistent with the above data, the degeneration of midbrain and striatum among 15-m Maged1 knockout mice was relatively mild compared to those in 15-m wild-type mice under physiological conditions.Conclusions: Maged1 deficiency-mediated apoptosis inhibition and autophagy enhancement may be a potential pro-survival mechanism during the progression of PD.

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Abstract 5555: Honokiol inhibits tumor growth in a xenograft melanoma mice model and activates the apoptotic signaling pathway in vivo.

10.1158/1538-7445.am2013-5555 ◽

2013 ◽

Author(s):

Ruth F. Guillermo ◽

Sreevidya Santha ◽

Jonathan Stevens ◽

Emily Coughlin ◽

Pious Patel ◽

...

Keyword(s):

Tumor Growth ◽

Signaling Pathway ◽

Mice Model ◽

Apoptotic Signaling

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