Publications by authors named "Cuicui Shi"

10 Publications

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Cyclin-dependent kinase inhibitor roscovitine attenuates liver inflammation and fibrosis by influencing initiating steps of liver injury.

Clin Sci (Lond) 2021 Apr;135(7):925-941

Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China.

Liver diseases present a significant public health burden worldwide. Although the mechanisms of liver diseases are complex, it is generally accepted that inflammation is commonly involved in the pathogenesis. Ongoing inflammatory responses exacerbate liver injury, or even result in fibrosis and cirrhosis. Here we report that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, exerts beneficial effects on acute and chronic liver inflammation as well as fibrosis. Animal models of lipopolysaccharide (LPS)/d-galactosamine- and acute or chronic CCl4-induced liver injury showed that roscovitine administration markedly attenuated liver injury, inflammation and histological damage in LPS/d-galactosamine- and CCl4-induced acute liver injury models, which is consistent with the results in vitro. RNA sequencing (RNA-seq) analysis showed that roscovitine treatment repressed the transcription of a broad set of pro-inflammatory genes involved in many aspects of inflammation, including cytokine production and immune cell proliferation and migration, and inhibited the TGF-β signaling pathway and the biological process of tissue remodeling. For further validation, the beneficial effect of roscovitine against inflammation was evaluated in chronic CCl4-challenged mice. The anti-inflammation effect of roscovitine was observed in this model, accompanied with reduced liver fibrosis. The anti-fibrotic mechanism involved inhibition of profibrotic genes and blocking of hepatic stellate cell (HSC) activation. Our data show that roscovitine administration protects against liver diseases through inhibition of macrophage inflammatory actions and HSC activation at the onset of liver injury.
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http://dx.doi.org/10.1042/CS20201111DOI Listing
April 2021

Hepatitis B-related glomerulonephritis and optimization of treatment.

Expert Rev Gastroenterol Hepatol 2020 Feb 23;14(2):113-125. Epub 2020 Jan 23.

Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

: Multiple studies have revealed a strong relationship between the development of nephropathy and hepatitis B virus (HBV) infection. The underlying pathogenesis of hepatitis B-related glomerulonephritis (HBV-GN) involves immune complexes, which can be isolated from kidney tissues. Clearance of HBV antigenemia improves renal impairment and proteinuria in HBV-GN patients.: In this review, we present our current understanding of the epidemiology, pathogenesis, pathology, diagnosis, and treatment of HBV-GN. We discuss the advantages and disadvantages of oral nucleoside/nucleotide analogs (NAs), and the main pharmaceutical treatment for hepatis B.: Currently, antiviral agents are the main HBV-GN therapeutic agents. Although no randomized controlled clinical trials have compared the efficacy of interferon (IFN) and NA, we suggest IFN treatment for pediatric patients (IFN-α in patients ≥1 year; pegIFN-α in patients ≥3 years) considering treatment duration and absence of resistance. Novel NAs have brought about promising treatment options involving high efficacy viral suppression and low resistance rates. NAs with a high barrier to resistance (e.g. entecavir) are recommended as first-line therapy of HBV-GN. Immunosuppression monotherapy, such as corticosteroids, is of little benefit and potentially harmful to HBV-GN patients due to the possibility of viral reactivation.
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http://dx.doi.org/10.1080/17474124.2020.1717948DOI Listing
February 2020

Protective Effects of Oridonin on Acute Liver Injury via Impeding Posttranslational Modifications of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) in the Toll-Like Receptor 4 (TLR4) Signaling Pathway.

Mediators Inflamm 2019 12;2019:7634761. Epub 2019 Sep 12.

Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.

Objective: Recent researches have demonstrated that inflammation-related diseases are effectively regulated by posttranslational modifications (PTMs) including phosphorylation and acetylation. Our previous study found a new acetyltransferase inhibitor, oridonin, which had a protective effect on acute liver injury (ALI). In the present study, we further investigated its protective mechanism against D-galactosamine (D-Gal) combined with lipopolysaccharide- (LPS-) induced ALI in mice.

Methods: Intraperitoneal injections of LPS (40 g/mouse)/D-Gal (5 mg/mouse) were given to the mice, and the experimental group was pretreated with intraperitoneal injection of oridonin (0.2 mg/mouse). To elucidate the protective mechanism of oridonin, we collected liver specimens and used RNA-sequencing (RNA-Seq) analysis. We focused on the genes that were upregulated by LPS/D-Gal and downregulated after pretreatment with oridonin. The downregulated genes examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were further verified by real-time polymerase chain reaction (PCR) and western blot.

Results: GO analysis showed that genes that were downregulated after pretreatment with oridonin were extremely concentrated in immune response, chemotaxis, and inflammatory response. Real-time PCR confirmed that the expression of these genes was upregulated by LPS/D-Gal induction and reduced after treatment with oridonin, which was consistent with RNA-Seq results. KEGG pathway analysis showed a significantly enriched downregulated gene that was present in the Toll-like receptor (TLR) 4 signaling cascade. Our results manifested that phosphorylation levels of upstream signaling molecules in the TLR4 signaling cascade, including extracellular signal-regulated kinase (ERK), P38, and IB, were significantly inhibited by oridonin. Furthermore, LPS/D-Gal stimulation triggered posttranslational modifications of related gene loci in the TLR4 signaling pathway, including phosphorylation of IL-1 receptor-associated kinase 4 (IRAK4 T345/S346) and acetylation of IRAK4 (K34). However, after treatment with oridonin, the modification pattern of IRAK4 expression stimulated by LPS/D-Gal was suggestively attenuated.

Conclusion: Our study revealed that the protective effects of oridonin on LPS/D-Gal-induced ALI mediated by inhibition of the PTMs of IRAK4, including phosphorylation of T345/S346 and acetylation of K34.
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http://dx.doi.org/10.1155/2019/7634761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757283PMC
April 2020

Multiple foci modulation with controllable positions and intensity ratios through decomposed optimization.

Opt Lett 2019 May;44(9):2354-2357

In this Letter, multiple foci modulation with controllable positions and intensity ratios is presented with a multi-belt binary phase mask in a tightly focusing system. Different from previous methods, the diffractive optical element (DOE) in our model is first virtually decomposed into two or more simple sub-DOEs. Then, after optimization, the sub-DOEs are combined to form the desired DOE through superposition. By such a decomposed optimization, the optimization complexities are greatly reduced, and the calculation becomes simpler and more effective. Furthermore, since the quantities and structures of sub-DOEs can be adjusted according to the original DOE, the method is very flexible and adaptable. As a demonstration, up to nine foci on the optical axis are studied, and the simulation results show that multiple foci can be well modulated. The proposed method may provide a universal strategy for complex light field modulations in a simple way.
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http://dx.doi.org/10.1364/OL.44.002354DOI Listing
May 2019

Fabrication of high fill factor cylindrical microlens array with isolated thermal reflow.

Appl Opt 2018 Sep;57(25):7296-7302

We demonstrate a simple, controllable, and stable method for fabricating high fill factor cylindrical microlens array with a novel isolated thermal reflow process. In this method, microstripes with a very small gap were obtained via digital micromirror device-based lithography, then covered with polydimethylsiloxane (PDMS) solution. The prepared microstripes were isolated and were heated and reflowed to a cylindrical microlens array. During the reflow process, the semicross-linked PDMS can serve as a barrier to prevent the diameter change and the bonding of adjacent microlenses. By this special treatment, the fill factor of the cylindrical microlens array can be significantly improved. Moreover, the reflow time and temperature have very little effect on the microlens shape due to the surrounded semicross-linked PDMS. This will make our process stabler than traditional methods. The measured 3D profile is good and satisfactory, and excellent optical performance is demonstrated with the fabricated cylindrical microlens arrays. The proposed method may offer a viable route for fabrication of high fill factor microlens arrays in a very simple and stable way.
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http://dx.doi.org/10.1364/AO.57.007296DOI Listing
September 2018

Oridonin ameliorates lipopolysaccharide/D-galactosamine-induced acute liver injury in mice via inhibition of apoptosis.

Am J Transl Res 2017 15;9(9):4271-4279. Epub 2017 Sep 15.

Department of Gastroenterology, Shanghai Tongren Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai 200336, China.

We investigated the protective effects exerted by oridonin, the main active constituent of the Chinese medicinal herb , against lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute liver injury (ALI). An ALI model was induced in mice using LPS (40 μg/0.5 ml) and D-Gal (5 mg/0.5 ml). The mice were randomly divided into the following five groups of six mice each: one control group (a), one ALI group (b), two oridonin treatment groups (c and d), and one oridonin control group (e). Oridonin (0.2 mg/0.5 ml) was administered once 1 h prior to the LPS/D-Gal challenge in group c and a total of three times over a period of four days, with the last dose given at 1 h before the LPS/D-Gal challenge, in group d. Pretreatment with oridonin improved the survival rate, alleviated histopathological abnormalities, and suppressed plasma aminotransferases in the LPS/D-Gal-challenged mice. Importantly, oridonin attenuated LPS/D-Gal-induced apoptosis in hepatocytes by reducing pro-apoptotic signals (P<0.05), such as tumor necrosis factor-α (TNF-α) and c-Jun N-terminal kinases (JNK). Furthermore, JNK-associated mitochondrial pro-apoptotic proteins were also suppressed by pretreatment with oridonin. Taken together, these data show that oridonin exerts protective effects against LPS/D-Gal-induced ALI in mice via a mechanism that may involve the suppression of the pro-apoptotic cytokine TNF-α and JNK-associated pro-apoptotic signaling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622269PMC
September 2017

Role of CTGF gene promoter methylation in the development of hepatic fibrosis.

Am J Transl Res 2016 15;8(1):125-32. Epub 2016 Jan 15.

Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.

Connective tissue growth factor (CTGF) plays a critical role in the hepatic stellate cells (HSCs)-mediated development of hepatic fibrosis. Nevertheless, the effects of CTGF gene promoter methylation in the pathogenesis of hepatic fibrosis remain largely unknown. In the current study, we isolated and overexpressed CTGF in primary HSCs. We analyzed the CTGF gene promoter methylation inHSCs that undergo a phenotypic change into myofibroblast-like cellsthat express α-smooth muscle actin (α-SMA) in vitro and in vivo in a CCl4-induced rat hepatic fibrosis model. We found that CTGF promoted the phenotypic changes of HSCs into myofibroblasts in vitro, while inhibition of CTGF promoter methylation augmented the process, suggesting that CTGF gene promoter methylation may negatively regulate hepatic fibrosis. In vivo, CCl4 induced hepatic fibrosis in rats, and the severity of hepatic fibrosis inversely correlated with the levels of CTGF gene promoter methylation in HSCs. Together, our data demonstrate that CTGF gene promoter methylation may prevent the development of hepatic fibrosis, and low level of CTGF gene promoter methylation in HSCs may be a predisposing factor for developing liver fibrotic disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759422PMC
April 2016

Characterization and flocculability of a novel proteoglycan produced by Talaromyces trachyspermus OU5.

Authors:
Di Fang Cuicui Shi

J Biosci Bioeng 2016 Jan;121(1):52-56

College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095, China; College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China.

A filamentous fungus strain OU5 was isolated from a soil sample for its ability to produce rich exopolymers (EPS), with high flocculation capability towards kaolin suspension and swine wastewater, at low-carbon source conditions. EPS from strain OU5 was extracted and characterized to determine its flocculating behavior and active constituents involved in the flocculation. Strain OU5 was identified as Talaromyces trachyspermus by 18S rDNA-ITS gene sequencing and morphological observation. The extracted EPS was a novel proteoglycan (designated as BF-OU5) composed of 84.6% (w/w) polysaccharides and 15.2% (w/w) proteins. The enzymatic digestion tests revealed that the polysaccharides in BF-OU5, composed of 67% glucose, 16.4% mannose, 8.6% xylose and 8% galactose, contributed to 99.7% of flocculating capacity and were the major active ingredients in the flocculation. By contrast, the proteins in BF-OU5 only had minor roles in the flocculation. The presence of hydroxyl, amide, carboxyl and methoxyl functional groups in BF-OU5, and the high molecular weight (1.053 × 10(5)-2.970 × 10(5) Da) as well as the structure of a spherical conformation with inner pores and channels made of cross-linked netted textures contributed to the flocculation. A dosage of 20 mg/l BF-OU5 initiated more than 92.5% of flocculating efficiency towards kaolin suspension without any added coagulants; its flocculability was stable over a wide range of pH (4.0-8.0) and temperature (20°C-100°C). Treatment of swine wastewater using BF-OU5 achieved 52.1% flocculating removal for chemical oxygen demand, 39.7% for Kjeldahl nitrogen, 18.6% for NH4(+)-N, 21.5% for total phosphorus, and 75% for turbidity.
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http://dx.doi.org/10.1016/j.jbiosc.2015.05.001DOI Listing
January 2016

Up-regulation of CXCR4 in rat umbilical mesenchymal stem cells induced by serum from rat with acute liver failure promotes stem cells migration to injured liver tissue.

Mol Cell Biochem 2014 Nov 7;396(1-2):107-16. Epub 2014 Aug 7.

Department of Infectious Diseases, First Hospital Affiliated to Suzhou University, Suzhou, 215006, Jiangsu, China.

The role of C-X-C chemokine receptor type 4 (CXCR4) in umbilical mesenchymal stem cells (UMSCs) as therapy for liver disease is ill understood. The aim of the study was to evaluate rat UMSCs (rUMSCs) on CXCR4 expression and homing to injured liver tissue. rUMSCs were isolated from umbilical cords of pregnant rats. Acute liver failure (ALF) models were developed using D-galactosamine. CXCR4 expression induction by serum from rats with ALF (LFS), cytokines, growth factors, and LPS was analyzed. CXCR4 expression was analyzed by RT-PCR, western blot, and flow cytometry. rUMSCs were labeled with carboxyfluorescein and pretreated with LFS to induce CXCR4 expression and were transplanted into ALF rats. Animals were sacrificed 48 h and 1 week after transplantation. Liver-homing rUMSCs were observed under fluorescence microscopy. rUMSCs were successfully isolated, expressing CD90 and CD106, but not CD34 and CD45. mRNA and protein expressions of CXCR4 were strongly up-regulated by LFS and by the mixture of cytokines, stem cell factor, and LPS (CM). Expression of cell surface CXCR4 on rUMSCs in groups treated with LFS (42.37 ± 1.60 %) and CM (40.17 ± 1.78 %) was higher than that in the untreated control group (9.67 ± 1.06 %) (both P < 0.001). At 48 h after transplantation, more rUMSCs pretreated with LFS appeared in the portal area, and migrated to the liver parenchyma after 1 week. LFS strongly induced the surface expression of CXCR4 on rUMSCs. Increasing CXCR4 expression on rUMSCs may enhance their homing ability to injured liver tissue, and may eventually be used for treating liver diseases.
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http://dx.doi.org/10.1007/s11010-014-2147-7DOI Listing
November 2014

Inhibition of lipopolysaccharide-induced iNOS and COX-2 expression by indole alkaloid, 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one, via NF-κB inactivation in RAW 264.7 macrophages.

Planta Med 2013 Jun 13;79(9):782-7. Epub 2013 May 13.

School of Pharmacy, Yantai University, Yantai, PR China.

3-(Hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one is a bioactive indole alkaloid isolated from Nauclea officinalis, a plant species which is used as a traditional Chinese medicine. We investigated the anti-inflammatory properties of 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one in RAW 264.7 murine macrophages. The results indicated that it inhibited the overproduction of NO and the release of TNF-α. Furthermore, this compound inhibited the expression of iNOS and COX-2 proteins, the enzymatic activity of iNOS, and the translocation of NF-κB to the nucleus induced by LPS. Therefore, we suggested that the effect of 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one-mediated inhibition of the expression of LPS-induced iNOS and COX-2 genes is due to the suppression of NF-κB activation in the transcriptional level.
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http://dx.doi.org/10.1055/s-0032-1328550DOI Listing
June 2013