Surface-Displayed Porcine IFN-λ3 in Lactobacillus plantarum Inhibits Porcine Enteric Coronavirus Infection of Porcine Intestinal Epithelial Cells

Yong-Shi Liu,Qiong Liu,Yanlong Jiang,Wentao Yang,Hai-Bin Huang,Chun-Wei Shi,Gui-Lian Yang,Chun-Feng Wang 한국미생물·생명공학회 2020 Journal of microbiology and biotechnology Vol.30 No.4

Interferon (IFN)-λ plays an essential role in mucosal cells which exhibit strong antiviral activity. Lactobacillus plantarum (L. plantarum) has substantial application potential in the food and medical industries because of its probiotic properties. Alphacoronaviruses, especially porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), cause high morbidity and mortality in piglets resulting in economic loss. Co-infection by these two viruses is becoming increasingly frequent. Therefore, it is particularly important to develop a new drug to prevent diarrhea infected with mixed viruses in piglets. In this study, we first constructed an anchored expression vector with CWA (C-terminal cell wall anchor) on L. plantarum. Second, we constructed two recombinant L. plantarum strains that anchored IFN-λ3 via pgsA (N-terminal transmembrane anchor) and CWA. Third, we demonstrated that both recombinant strains possess strong antiviral effects against coronavirus infection in the intestinal porcine epithelial cell line J2 (IPEC-J2). However, recombinant L. plantarum with the CWA anchor exhibited a more powerful antiviral effect than recombinant L. plantarum with pgsA. Consistent with this finding, Lb.plantarum-pSIP-409-IFN- λ3-CWA enhanced the expression levels of IFN-stimulated genes (ISGs) (ISG15, OASL, and Mx1) in IPEC-J2 cells more than did recombinant Lb.plantarum-pSIP-409-pgsA'-IFN-λ3. Our study verifies that recombinant L. plantarum inhibits PEDV and TGEV infection in IPEC-J2 cells, which may offer great potential for use as a novel oral antiviral agent in therapeutic applications for combating porcine epidemic diarrhea and transmissible gastroenteritis. This study is the first to show that recombinant L. plantarum suppresses PEDV and TGEV infection of IPEC-J2 cells.

Chinese Patients with Gastric Cancer Need Targeted Adjuvant Chemotherapy Schemes

Shi, Wen-Tao,Wei, Lei,Xiang, Jin,Su, Ke,Ding, Qiong,Tang, Meng-Jie,Li, Ji-Qiang,Guo, Yi,Wang, Pu,Zhang, Jing-Wei Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Background: Gastric cancer (GC) is one of the most common cancers in China. Adjuvant chemotherapy (AC) is a routine auxiliary treatment for GC recommended by the guidelines issued in 2011 by the Ministry of Health of the People's Republic of China, but the relevant credible consequences in China have been insufficient because of China's late start and ethical concerns. Methods: A series of databases, including Cochrane Library, MEDLINE, EMBASE, the Chinese database of the National Knowledge Infrastructure and the VIP database, were searched by 2 reviewers independently for studies investigating AC for GC through March 2012. The retrieved literature was screened according to the eligibility criteria. Results: A total of 35 randomized control trials (RCTs) were subjected to the final analysis, including 4,043 patients in treatment group and 3,884 in the control group, as well as 4 clinical-control trials (CCTs), which accessed the final analysis with 238 and 252 patients, respectively. AC reduced the risk of death as a protective treatment with statistical significance (HR=0.91, 95%CI: [0.85, 0.97], P=0.002), and it seemed more effective for Asian than non-Asian patients. The effects of AC were not influenced by the starting time (P>0.05). D2 lymphadenectomy-based chemotherapy was effective (HR=0.89, 95%CI: [0.80, 0.99], P=0.04). Oral S-1 40 mg/m2 after D2 lymphadenectomy might be a better choice for Asians with advanced GC and might result in a greater reduction of adverse events than in non-Asian patients. GRADE quality assessment determined that the strength of the evidence from foreign studies from Europe, the United States and Asian countries other than China was high, while it was moderate for Chinese studies. Conclusion: AC was effective or even curative in Chinese patients in general, although it is still necessary to optimize a targeted AC scheme for Chinese patients with GC.

B-cell Lymphoma 2 rs17757541 C>G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

Li, Qiong,Yin, Jun,Wang, Xu,Wang, Li-Ming,Shi, Yi-Jun,Zheng, Liang,Tang, Wei-Feng,Ding, Guo-Wen,Liu, Chao,Liu, Rui-Ping,Gu, Hai-Yong,Sun, Jia-Ming,Chen, Suo-Cheng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.

Matrix Metalloproteinase-9 as a Prognostic Factor in Gastric Cancer: A Meta-Analysis

Zhang, Qiong-Wen,Liu, Lei,Chen, Ru,Wei, Yu-Quan,Li, Ping,Shi, Hua-Shan,Zhao, Yu-Wei Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Background: Matrix metalloproteinase-9 (MMP-9) is associated with disruption of basement membranes of blood vessels and promotion of metastasis through the lymphatics. However, its prognostic value for survival in patients with gastric cancer remains controversial. Method: We therefore conducted a meta-analysis of the published literature in order to clarify the impact of MMP-9. Clinical studies were selected for further analysis if they provided an independent assessment of MMP-9 in gastric cancer and reported analysis of survival data according to MMP-9 expression. Results: A total of 11 studies, covering 1700 patients, were included for meta-analysis. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive MMP-9 expression had an impact on overall survival: 1.25 (95% confidence interval 1.11-1.40) in all eligible studies; 1.13 (1.06-1.20) in 8 studies detecting MMP-9 by immunohistochemistry; 1.36 (1.12-1.65) in 7 studies from Asia. Only one study for DFS showed a significant impact on disease free survival (HR 1.73, 95%CI 1.27-2.34). Conclusions: Our findings suggested that MMP-9 protein expression might be a factor for a poor prognosis in patients with gastric cancer. However, the association was rather weak, so that more prospective studies should further explore the prognostic impact of MMP-9 mRNA and correlations between MMP-9 and clinicopathological characteristics.

Long non-coding RNA NEAT1 decreases the chemosensitivity of gastric cancer cells via regulating P-glycoprotein expression

Jian Wang,Qiong Niu,Ning Shi,Chengxia Liu,Haifeng Lian,Jiancheng Li,Kun Li,K. Li 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.3

Drug resistance remains to be one of the major challenges in clinical treatment of gastric cancer (GC). Accumulating evidences have highlighted the involvement of long non-coding RNA (lncRNA) in carcinogenesis, chemoresistance, and metastasis. NEAT1, a recently identified lncRNA, was identified as an oncogene to regulate carcinogenesis. This present study aimed to investigate the role of NEAT1 in the drug resistance in GC. Our study found that NEAT1 expression was significantly upregulated in relapsed GC patients and cisplatin (CDDP)-resistant cell lines compared with primary GC patients and parental GC cell lines. NEAT1 upregulation was largely companied with the induction of P-gp. Overexpression of NEAT1 significantly increased the expression of several drug-resistance proteins, thereby compromising the sensitivity of GC cells to CDDP. In contrast, NEAT1 knockdown by RNAi did the opposite. Therefore, lncRNA NEAT1 is an important modulator for drug resistance of GC via promoting the expression of P-gp and other associated proteins.

Early Efficacy of Endostar Combined with Chemoradiotherapy for Advanced Cervical Cancers

Ke, Qing-Hua,Zhou, Shi-Qiong,Huang, Min,Lei, Yong,Du, Wei,Yang, Ji-Yuan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

The aim of this study was to investigate the early outcome of Endostar combined with chemoradiotherapy for advanced cervical cancer. Fifty-two cases (FIGO IIb to IVa) were divided randomly into two groups, receiving chemoradiotherapy alone (CRT group) and Endostar combined with chemoradiotherapy (CRT+E group). For the patients in the CRT+E group, Endostar was administered daily with the dosage of 7.5 $mg/m^2$, and cisplatin was administered weekly with the dosage of 20 $mg/m^2$ during the radiation. The regimens lasted for 4 weeks with no difference in chemoradiotherapy between the two groups. The early outcome complete remission rate was 73.1%, partial remission rate was 23.1% and the total response rate was 96.2% in CRT+E group, a significant improvement on the 34.6%, 42.3% and 76.9%, respectively, in the CRT group. One year survive rates were 100% and 84.6% in the CRT+E group and CRT groups, the difference being significant. Endostar combined with chemoradiotherapy can improve the early outcome of the advanced cervical cancer, and adverse effects were not encountered.

Early Efficacy of Taxotere and Cisplatin Chemo-Radiotherapy for Advanced Cervical Cancer

Ke, Qing-Hua,Zhou, Shi-Qiong,Du, Wei,Lei, Yong,Huang, Min,Luo, Fei,Yang, Ji-Yuan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

The aim of this study was to investigate the early outcome of the taxotere and cisplatin chemoradiotherapy for advanced cervical cancer. Fifty-six cases (FIGO II b to IVa) were divided randomly into two groups: radiotherapy alone (28 cases) and radiation plus chemotherapy (TP) group. There was no difference in radiotherapy between the two groups. The RT+C cases who received TP regimen during the radiation, and DDP once weekly injection of vain, according to 20$mg/m^2$ and taxotere once weekly iv according to 35 $mg/m^2$. These regimens were given for 4~5weeks, and some medicines to control vomiting were available for the RT+C cases. The two groups received an oral medicine MA 160mg every day during the treatment. Regarding early outcome, the complete remission rate was 64.3% and partial remission rate was 35.7% in RT+C. The complete remission rate was 32.1% and partial remission rate was 39.3% in RT. The total response rate and complete remission in the RT+C group were higher than that in the RT group. We conclude that taxotere and cisplatin chemoradiotherapy can improve the early outcome of the advanced cervical cancer, the adverse effects being endurable.

Genipin-Crosslinked, Immunogen-Reduced Decellularized Porcine Liver Scaffold for Bioengineered Hepatic Tissue

Xiujuan Wu,Yujia Wang,Qiong Wu,Yi Li,Li Li,Jing Tang,Yujun Shi,Hong Bu,Ji Bao,Mingjun Xie 한국조직공학과 재생의학회 2015 조직공학과 재생의학 Vol.12 No.6

Liver disease affects millions of patients each year worldwide. Decellularized biologic matrices are plausible biomedical materials for bioengineered replacement hepatic tissue. However, one of the concerns for its safe medical application is the lack of objective assessment of the immunogen within the materials and in vivo immune responses to the matrices. The purpose of this study was to produce immunogen- reduced and biocompatible matrices from porcine liver. Whole porcine livers were perfusion decellularized and cross-linked with glutaraldehyde (GA) or genipin (GP). Proteins were extracted, and the migratory response of human leukocytes toward protein extracts was examined using an in vitro migration chamber. In addition, biopsy specimens of decellularized scaffolds were implanted subcutaneously into rodents to investigate scaffold immunogenicity. Histological staining confirmed cellular clearance from pig livers, with removal of nuclei and cytoskeletal components and widespread preservation of structural extracellular molecules. Polymerase chain reaction analysis showed that galactose-alpha-1,3-galactose-beta-1,4-N-acetylglucosamine (1,3 gal), swine leukocyte antigen, and porcine endogenous retrovirus were completely removed in the matrices. Decellularization significantly reduced the migration of monocytes compared with native porcine tissue. Although the proportion of transmigrating lymphocytes was much lower, repeating the cross-linking procedure reduced the migratory response. After implantation for 4 weeks, the decellularized and native samples were degraded, and the GA-treated group demonstrated a severe inflammatory reaction; however, minimal inflammatory cell infiltration was seen in the GPtreated group during the 8-week investigation period. In conclusion, our study provided evidence that GP crosslinking could significantly reduce the immunogenicity of decellularized liver biomaterials.

Combinatorial nanococktails via selfassembling lipid prodrugs for synergistically overcoming drug resistance and effective cancer therapy

Tongyu Li,Weiwei Shi,Jie Yao,Jingyun Hu,Qiong Sun,Jing Meng,Jian Wan,Haihan Song,Hangxiang Wang 한국생체재료학회 2022 생체재료학회지 Vol.26 No.1

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/sicircPRMT5 regulated the miR-30c/SNAIL1/E-cadherin axis, inhibiting bladder cancer growth and progression. Conclusion: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer. Keywords: Synthesized chrysotile nanomaterials, Gene therapy, Targeted delivery, CircPRMT5, SiRNA, Bladder cancer

Two new tirucallane triterpenoids from the leaves of Aquilaria sinensis

Jin Tang Cheng,Ya Qiong Han,Juan He,Xing De Wu,Liao Bin Dong,Li Yan Peng,Yan Li,Qin Shi Zhao 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.9

Two new tirucallane triterpenoids, aquilacallanesA–B (1–2), together with 15 known compounds(3–17) were isolated from the leaves of Aquilaria sinensis. The structures of these new compounds were elucidated onthe basis of extensive spectroscopic analyses. All compoundswere evaluated for their cytotoxic activity againstfive human cancer cell lines. The known compounds,ursolic acid (7) and 5,7,40-trimethoxyflavone (14), exhibitedweak cytotoxic activity against some cells.