Publications by authors named "Rongrong Cheng"

5 Publications

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The outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates the depression-like behavior of depressed mice induced by chronic stress.

Biochem Biophys Res Commun 2021 Aug 12;566:170-176. Epub 2021 Jun 12.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Akkermansia muciniphila is a symbiotic intestinal bacterium with a high medicinal value. Amuc_1100 is the outer membrane protein of A. muciniphila and plays an important role in the interaction between A. muciniphila and its host. The objective of this study was to evaluate the antidepressant activity of Amuc_1100 in a chronic unpredictable mild stress (CUMS) model. Amuc_1100 intervention ameliorated CUMS-induced depression-like behavior and CUMS-induced down-regulation of serotonin (5-hydroxytryptamine, or simply, 5-HT) in the serum and colon of mice. Microbial analysis of mouse feces showed that Amuc_1100 could improve the gut microbiota dysregulation induced by CUMS. In addition, Amuc_1100 intervention could also improve the down-regulation of brain-derived neurotrophic factor (BDNF) and inflammation in the hippocampus induced by CUMS. These results suggest that Amuc_1100 has a good antidepressant effect, and the mechanism may be related to the improvement of gut microbiota, the up-regulation of the BDNF level, and the inhibition of the neuroinflammatory response.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.018DOI Listing
August 2021

The outer membrane protein Amuc_1100 of promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling.

Food Funct 2021 Apr;12(8):3597-3610

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China. and Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei 230601, Anhui, China.

Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.
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http://dx.doi.org/10.1039/d1fo00115aDOI Listing
April 2021

Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response.

J Ethnopharmacol 2020 Jun 9;255:112556. Epub 2020 Jan 9.

The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Ethnopharmacological Relevance: Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China.

Aim Of The Study: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis.

Materials And Methods: C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism.

Results: The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ.

Conclusion: Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α.
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http://dx.doi.org/10.1016/j.jep.2020.112556DOI Listing
June 2020

Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2-mediated signaling.

Neuro Oncol 2019 11;21(11):1423-1435

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Glioblastoma (GBM) is the most malignant primary brain tumor, with dismal median survival. Treatment of GBM is particularly challenging given the intrinsic resistance to chemotherapy and difficulty of drugs to reach the tumor beds due to the blood-brain barrier. Here, we examined the efficacy of SHP099, a potent, selective, and oral SHP-2 inhibitor for treating GBM with activated platelet derived growth factor receptor alpha (PDGFRα) signaling.

Methods: The effects of SHP099 on cell survival of neural progenitor cells (NPCs), GBM cell lines, and patient-derived glioma stem-like cells (GSCs) were evaluated. Brain and plasma pharmacokinetics of SHP099 and its ability to inhibit SHP-2 signaling were assessed. SHP099 efficacy as a single agent or in combination with temozolomide (TMZ) was assessed using transformed mouse astrocyte and GSC orthotopic xenograft models.

Results: Activated PDGFRα signaling in established GBM cells, GSCs, and transformed mouse astrocytes was significantly inhibited by SHP099 compared with NPCs in vitro and in vivo through targeting SHP-2-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 in GBM. SHP099 treatment specifically inhibited expression of JUN, a downstream effector of PDGFR signaling, thereby attenuating cell cycle progression in GBM cells with activated PDGFRα. Moreover, SHP099 accumulated at efficacious concentrations in the brain and effectively inhibited orthotopic GBM tumor xenograft growth. SHP099 exhibited antitumor activity either as a single agent or in combination with TMZ and provided significant survival benefits for GBM tumor xenograft-bearing animals.

Conclusions: Our data demonstrate the utility and feasibility of SHP099 as a potential therapeutic option for improving the clinical treatment of GBM in combination with TMZ.
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http://dx.doi.org/10.1093/neuonc/noz107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827835PMC
November 2019

Comparison of the Efficacy of Different Analgesia Treatments for Total Knee Arthroplasty: A Network Meta-Analysis.

Clin J Pain 2018 11;34(11):1047-1060

Department of Orthopedics, Jianhu People's Hospital of Jiangsu Province, Yancheng, Jiangsu, China.

Background And Aim: The severe pain after total knee arthroplasty (TKA) brings many patients more suffering, longer hospital stay, and higher expenses. This study was designed to assess the relative efficacy of several clinical treatments for postoperative analgesia of TKA through network meta-analysis based on multiple published randomized controlled trials.

Methods: Embase and PubMed were utilized to conduct this network meta-analysis from inception until 2016. Pain score, morphine consumption (milligrams), and length of hospitalization (day) were selected as the endpoints.

Results: A total of 58 studies with 3501 patients were included in this network meta-analysis. Except for patient-controlled epidural analgesia+femoral nerve block (FNB) and sciatic nerve block, all treatments were significantly superior to placebo in pain score 6 to 8 hours. In terms of pain score 24 hours, only continuous femoral nerve block (cFNB), periarticular infiltration, periarticular infiltration+FNB, single-dose FNB, and sciatic nerve block+FNB exhibited better performance than control group. For pain score 48 hours after surgery, only cFNB and intra-articular infiltration yielded better results than control group [standard mean difference=-0.68, 95% credible intervals (CrIs)=-1.03 to -0.33; standard mean difference=-0.53, 95% CrIs=-1.07 to -0.01, respectively]. Only cFNB exhibited better results with respect to morphine consumption day 2 after surgery (mean difference=-12.95, 95% CrIs=-19.70 to -6.53).

Conclusions: Considering both pain score and morphine consumption, cFNB was potentially the most efficacious postoperative treatment for patients undergoing TKA.
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http://dx.doi.org/10.1097/AJP.0000000000000631DOI Listing
November 2018
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