Circular RNA expression profile of systemic lupus erythematosus and its clinical significance as a potential novel biomarker

Li Wenyu,Fan Runge,Zhou Cheng,Wei Yue,Lin Shunsheng,Wen Sijian,Zeng Wen,Hou Wei,Zhao Cheng,Lin Youkun 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear. Objective: We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE. Method: RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis. Results: The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P < 0.05), and hsa_circ_0006689 expression in PBMCs correlated with the SLEDAI score (P < 0.05). Furthermore, addition of hsa_circ_0006689 expression increased the sensitivities of anti-dsDNA antibody and anti-Sm antibody levels for SLE diagnosis (from 29.03 to 61.30% and 32.26-71.00%, respectively). Conclusion: Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis.

Semi-solid State Fermentation of Food Waste for Production of Bacillus thuringiensis Biopesticide

Wenyu Zhang,Hui Zou,Lin Jiang,Juejun Yao,Jing Liang,Qunhui Wang 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.6

In this study, Bacillus thuringiensis (Bt) biopesticide was produced through different fermentation processes using food waste with different water contents. The semi-solid state sample with 75% water content presented the highest δ-endotoxin efficiency of 862 μg/mL. δ-endotoxin efficiency increased by 30.2% from that of the solid-state sample (50% water content) and 73.8% from that of the submerged sample (99% water content). Results confirmed that semi-solid state fermentation presents considerable advantages compared with other fermentation types (solid-state and submerged). The timing adjustment of pH and recycling fermentation effectively counteracted the inhibition of pH and product, thereby increasing δ- endotoxin efficiency to 1,648 and 2,478 μg/mL (accumulated value of all four fermentation loops), respectively. A δ- endotoxin slow-release formulation using polylactic acid as the carrier was also developed to effectively promote the stability of Bt biopesticide.

Acteoside and Acyl-Migrated Acteoside, Compounds in Chinese Kudingcha Tea, Inhibit α-Amylase In Vitro

Yuqin Lu,Wenyu Zhou,Yue Feng,Yao Li,Ke Liu,Lizhong Liu,Dongxu Lin,Zhendan He,Xuli Wu 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.6

Acteoside, the predominant polyphenol of small-leaved kudingcha, the Chinese tea, has various biological activities. In this study, we examined the acyl migration of acteoside to isoacteoside with high-temperature treatment of acteoside. The inhibitory effects of acyl-migrated acteoside and acteoside on α-amylase were investigated, as were their binding interaction with α-amylase. The binding of acteoside and isoacteoside to α-amylase was investigated by using the fluorescence spectra assay, circular dichroism, and protein–ligand docking studies. Acteoside was more effective than preheated acteoside and isoacteoside in inhibiting α-amylase activity. Acteoside and isoacteoside binding to α-amylase may induce conformational changes to α-amylase, and the binding site of acteoside and isoacteoside being near the active site pocket of α-amylase may explain the decreased activity of α-amylase. The different affinities and binding sites of acteoside and isoacteoside for α-amylase resulted in different inhibition rates, which may be due to structural differences between acteoside and isoacteoside.

Relaxation Effect of Schisandra Chinensis Lignans on the Isolated Tracheal Smooth Muscle in Rats and Its Mechanism

Cheng-Cheng Lin,Zhi-Ying Xu,Bi-Han Wang,Wenyue Zhuang,Jinghui Sun,He Li,JianGuang Chen,Chunmei Wang 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.8

Schisandra chinensis (S. chinensis) is one of the core drugs used for relieving cough and asthma in traditional Chinese medicine. However, there are few basic studies on the treatment of respiratory diseases with S. chinensis in modern pharmacology, and the material basis and mechanism of its antiasthmatic effect are still unclear. Lignans are the main active components of S. chinensis. The aim of this study was to observe the relaxation effect of S. chinensis lignans (SCL) on the tracheal smooth muscle of rats by in vitro tracheal perfusion experiments, and to explore the mechanism by preincubation with L-type calcium channel blocker verapamil, four potassium channel blockers glibenclamide, tetraethylamine, 4-aminopyridine and barium chloride (BaCl2), β-adrenoceptor blocker propranolol, nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME), and the cyclooxygenase inhibitor indomethacin, respectively. The results showed that SCL (0.25–1.75 mg/mL) reduced the contraction of isolated tracheal smooth muscle induced by acetylcholine, the preincubation with verapamil and glibenclamide could attenuate the relaxation effect, whereas propranolol, 4-aminopyridine, BaCl2, tetraethylamine, L-NAME, and indomethacin had no such effect. These results suggest that SCL has a significant relaxation effect on the isolated tracheal smooth muscle of rats, and the mechanism may be related to the inhibition of extracellular calcium influx and intracellular calcium release from the sarcoplasmic reticulum, as well as the activation of ATP-sensitive potassium channels. These findings may provide a pharmacological basis for the traditional use of S. chinensis to treat asthma.

Anwulignan alleviates D-galactose induced renal damage by regulating Nrf2/ARE signaling pathway in mice

Chunna Liu,Huijiao Lin,Liu Jiawei,Yao Wang,Chunmei Wang,Jinghui Sun,Chunyan Yu,Ying Dong,Wenyue Zhuang,Shu Jing,JianGuang Chen,He Li 한국식품과학회 2021 Food Science and Biotechnology Vol.30 No.8

Free radical accumulation in the body will cause oxidative stress damages including the renal damage. Schisandrae Sphenantherae Fructus (Schisandra), a traditional Chinese herbal medicine, has been used throughout the world. Anwulignan, a monomer extracted from Schisandra, has been shown in our previous studies to possess antioxidant and protective effects on the liver, brain and spleen damages in the aging mice. However, its effect on the renal damage caused by aging is not clear. This study showed that anwulignan could significantly increase the kidney index, the creatinine clearance, the activities of superoxide dismutase, catalase and glutathione peroxidase; reduce the urinary protein concentration, the serum urea nitrogen and creatinine content, the content of malondialdehyde and 8-hydroxylated deoxyguanosine in the renal tissue; and improve the renal tissue damage. Moreover, anwulignan increased the production of Nrf2, HO-1 and NQO1 proteins and decreased the production level of Keap1 protein in the renal tissue in the D-galactose induced aging mice. These results suggest that anwulignan significantly alleviates the renal damage by its antioxidant effect through regulating the production of Nrf2/ARE pathway-related proteins in the renal tissue in the D-galactose induced aging mice.

Secreted Tenascin C from Activated Hepatic Stellate Cells Promotes Epithelial-mesenchymal Transition in Hepatic Cancer Cell

( Sae Hwan Lee ),( Hong Jian ),( Xiao Liu ),( Wenyu Lin ),( Raymond T Chung ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Hepatic stellate cell (HSC) plays a pivotal role in hepatocarcinogenesis through direct effects on hepatocytes and modulation of the peri-tumoral stroma and immune response. A change in HSC secretory phenotype upon activation is closely correlated with increased proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells in vitro studies. Tenascin C (TNC) is a large hexameric extracellular matrix glycoprotein and highly expressed in several solid cancer including HCC. The aim of this study was to investigate the TNC expression by activated human HSC lines and the role of TNC in metastasis of HCC cells. Methods: Two HSC lines, LX2 and TWNT4, were stimulated with transforming growth factor-β for 48 hours and protein expression of TNC in media was evaluated with Western blot and ELISA. LX2 was transfected with TNC siRNA for 48 hours and was continued culture for 48 hours after media change. Huh7, hepatic cancer cell line, were incubated for 24 hours with conditioned media from TNC knockdown LX2. Epithelial-mesenchymal transition (EMT)-related genes expression of Huh7 were estimated by quantitative real-time reverse transcription. Results: TNC mRNA expressions were significantly increased in stimulated LX2 and TWNT4 and TNC protein in the media were also highly expressed in both activated HSC lines. TNC knockdown was successfully observed and TNC protein level was also significantly deceased in the media from TNC siRNA transfected LX2. E-cadherin expression was significantly increased and vimentin expression was decreased in Huh7 treated with conditioned media from TNC knockdown LX2. Conclusions: TNC expression was significantly increased in activated human HSC lines and secreted TNC from LX2 promote upregulation EMT in Huh7.

Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

Xueying Li,He Huang,Bing Xu,Hongqiang Guo,Yingcheng Lin,Sheng Ye,Jiqun Yi,Wenyu Li,Xiangyuan Wu,Wei Wang,Hongyu Zhang,Derong Xie,Jiewen Peng,Yabing Cao,Xingxiang Pu,Chengcheng Guo,Huangming Hong,Zhao 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3

Purpose Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. Materials and Methods Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. Results Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ! 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. Conclusion R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ! 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation

Chen Peng,Luo Xiaojun,Dai Guanqi,Jiang Yuchuan,Luo Yue,Peng Shuang,Wang Hao,Xie Penghui,Qu Chen,Lin Wenyu,Hong Jian,Ning Xue,Li Aimin 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Dexmedetomidine (DEX) is an anesthetic that is widely used in the clinic, and it has been reported to exhibit paradoxical effects in the progression of multiple solid tumors. In this study, we sought to explore the mechanism by which DEX regulates hepatocellular carcinoma (HCC) progression underlying liver fibrosis. We determined the effects of DEX on tumor progression in an orthotopic HCC mouse model of fibrotic liver. A coculture system and a subcutaneous xenograft model involving coimplantation of mouse hepatoma cells (H22) and primary activated hepatic stellate cells (aHSCs) were used to study the effects of DEX on HCC progression. We found that in the preclinical mouse model of liver fibrosis, DEX treatment significantly shortened median survival time and promoted tumor growth, intrahepatic metastasis and pulmonary metastasis. The DEX receptor (ADRA2A) was mainly expressed in aHSCs but was barely detected in HCC cells. DEX dramatically reinforced HCC malignant behaviors in the presence of aHSCs in both the coculture system and the coimplantation mouse model, but DEX alone exerted no significant effects on the malignancy of HCC. Mechanistically, DEX induced IL-6 secretion from aHSCs and promoted HCC progression via STAT3 activation. Our findings provide evidence that the clinical application of DEX may cause undesirable side effects in HCC patients with liver fibrosis.

MAPK4 silencing in gastric cancer drives liver metastasis by positive feedback between cancer cells and macrophages

Li Shuang,Guo Dongyang,Sun Qiang,Zhang Lu,Cui Yun,Liu Min,Ma Xixi,Liu Yiman,Cui Wenyu,Sun Leimin,Teng Lisong,Wang Liangjing,Lin Aifu,Liu Wei,Zhuo Wei,Zhou Tianhua 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Liver metastasis is a major cause of death in gastric cancer patients, but the underlying mechanisms are poorly understood. Through a combination of in vivo screening and transcriptome profiling followed by quantitative RT-PCR and tissue array analyses, we found that mitogen-activated protein kinase 4 (MAPK4) downregulation in gastric cancer tissues from patients is significantly associated with liver metastasis and poor prognosis. The knockdown of MAPK4 in gastric cancer cells promotes liver metastasis in orthotopic mouse models. MAPK4 depletion in gastric cancer cells induces the secretion of macrophage migration inhibitory factor (MIF) to polarize tumor-associated macrophages (TAMs) in orthotopic xenograft tumors. Moreover, TAMs activate epithelial–mesenchymal transition of gastric cancer cells to suppress MAPK4 expression, which further increases MIF secretion to polarize TAMs. Taken together, our results suggest a previously undescribed positive feedback loop between cancer cells and macrophages mediated by MAPK4 silencing that facilitates gastric cancer liver metastasis.