Targeting Orthotopic Glioma in Mice with Genetically Engineered Salmonella typhimurium

Wen, Min,Jung, Shin,Moon, Kyung-Sub,Jiang, Shen Nan,Li, Song-Yuan,Min, Jung-Joon The Korean Neurosurgical Society 2014 Journal of Korean neurosurgical society Vol.55 No.3

Objective : With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor models. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium (S. typhimurium) to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique. Methods : U87 malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated S. typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft. Results : The injected S. typhimurium exclusively localized in the glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of S. typhimurium in the brain tumors. Conclusion : The present study demonstrated that S. typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.

Chinese herbal medicine for drug-induced liver injury in patients with HIV/AIDS: A systematic review of randomized controlled trials

Zhang Xiao-wen,Li Jing,Hou Wen-Bin,Jiang Yue,Zheng Ruo-Xiang,Xu De-hao,Shen Chen,Robinson Nicola,Liu Jian-Ping 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.1

Background: To explore the effectiveness and safety of Chinese herbal medicine (CHM) for drug-induced liver injury (DILI) in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syn- drome (AIDS). Methods: A systematic search was made of eight databases (Pubmed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang, VIP, Sinomed) and two trial registries (WHO ICTRP, ClinicalTrials.gov) from in- ception to September 2022. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). The Cochrane Risk of Bias and Grading of Recommendations, Assess- ment, Development and Evaluations (GRADE) tools were used for quality appraisal. Results: Ten randomized controlled trials (RCTs) involving 732 participants were included. Comparing CHM alone with routine treatment, the CHM group showed lower aspartate aminotransferase (MD = -11.47 U/L, 95%CI[-13.05, -9.89], low certainty), lower alanine aminotransferase (MD = -2.68 U/L, 95%CI[-4.27, - 1.08], low certainty), lower total bilirubin (MD = -4.31 mmol/L, 95%CI[-5.66, -2.96], low certainty), lower bilirubin direct (MD = -3.19 mmol/L, 95%CI[-3.87, -2.51], low certainty), and higher effective rate (assessed by symptoms and liver indicators) (RR = 1.13, 95%CI[1.06, 1.20], low certainty). A significant difference was also found in CHM plus routine treatment versus routine treatment in the previous outcomes. No signif- icant difference was found on helper T cells among these comparisons. Only one RCT reported safety of CHM and found no adverse reaction during the trial. Conclusions: CHM may improve the liver function indices and effective rate for HIV/AIDS patients with DILI. However, the sample size was small and quality was low. Larger-samples of high-quality trials are needed.

Cytotoxicity of polymethyl methacrylate cement on primary cultured metastatic spinal cells

Ji Fang,Jieliang Shen,Wei Jiang,Wen Dong,Zhenming Hu,Zhenming Hu 대한독성 유전단백체 학회 2016 Molecular & cellular toxicology Vol.12 No.2

Polymethyl methacrylate (PMMA) bone cement has been commonly used for percutaneous injection into collapsed vertebral bodies due to malignant tumor. The purpose of this study was to investigate the possible mechanisms of PMMA’s cytotoxcity on primary cultured spinal metastastic cells (SMCs) in vitro. PMMA specimens were prepared in standard discs made of dough and polymerization stages, and the eluates were prepared following the ISO standard. Primary SMCs were obtained and isolated from 7 patients with spinal metastatic tumors undergoing vertebroplasty. Primary cultured SMCs were treated with PMMA specimens of different stages for 24 h, or co-cultured with extracted medium for successive 3 days. The temperatures in two locations from cement discs were recorded by K-type thermocouples. Furthermore, cell proliferation, apoptosis and cycles were determined by MTT and flow cytometry, respectively. The modulation of apoptotic proteins (bcl- 2, bax, caspase-3, caspase-8, Fas and PARP) and cell cycle proteins (cyclin D1, P21 and P27) were analyzed by western blot and real time PCR. The results of this study demonstrated that PMMA treatment was able to suppress SMCs proliferation, induce cell apoptosis and inhibit cell cycle arrest when compared to the control group in vitro (P<0.05). Simultaneously, the temperature recorded at the periphery of the PMMA specimen was not high enough to casue thermal injury. Furthermore, molecular markers of apoptosis including Fas, caspase-3 and caspase-9 activated, and Bcl-2/Bax dysregulated in the SMCs with PMMA stimulation. In addition, PMMA treatment showed decreased expression of cyclin D1 that induces cell cycle and increased epxression of inhibitory protein P21, with no significant difference of P27 expression. In summary, the present study confirms that PMMA cement can compromise the vitality and apoptosis of SMCs. This cytotoxic effect may be regulated by the biomarkers Fas, Bcl-2, Bax, caspase-3, caspase-9, cyclin D1 and P21, but not on account of thermal damage.

Pokemon Inhibits Transforming Growth Factor β-Smad4-Related Cell Proliferation Arrest in Breast Cancer through Specificity Protein 1

Ling Chen,Jing Zhong,Jiang-Hua Liu,Duan-Fang Liao,Ying-Ying Shen,Xiao-Lin Zhong,Xiao Xiao,Wen-Jun Ding,Xiu-Da Peng,Wei Xiong,Xu-Yu Zu 한국유방암학회 2019 Journal of breast cancer Vol.22 No.1

Purpose: Pokemon, also known as ZBTB7A, belongs to the POZ and Krüppel (POK) family of transcription repressors and is implicated in tumor progression as a key proto-oncogene. This present study aimed at determining the mechanism by which Pokemon inhibits transforming growth factor β (TGFβ)-Smad4 pathway-dependent proliferation arrest of breast cancer cells via specificity protein 1 (SP1). Methods: Over-expressing plasmid or small interfering RNA (siRNA) transfection was used to regulate Pokemon levels. The EdU incorporation assay, MTS assay, and clone formation were used to identify the inhibitory effect of Pokemon siRNA on cell proliferation. Quantitative real-time polymerase chain reaction assay confirmed that Pokemon deletion inhibited the expression of proliferation-associated genes. The dual-luciferase reporter assay, electrophoretic mobility shift assay, and co-immunoprecipitation assay were used to analyze binding between Pokemon, Smad4, and SP1. Results: Pokemon deletion induced proliferation arrest of breast cancer cells and inhibited the expression of proliferation-associated genes, especially Smad4. Pokemon bound with SP1 to interdict Smad4 promoter activity. Information on clinical samples was obtained from The Cancer Genome Atlas data, in which the Pokemon mRNA levels showed a negative correlation with Smad4 levels in different subtypes of breast cancer in two independent datasets. Conclusion: We demonstrated that Pokemon binds to SP1 to down-regulate Smad4 expression, thereby promoting proliferation of breast cancer cells. This suggests that Pokemon is a potential TGFβ-signaling participant in breast cancer progression.

Analysis of chemical compounds and toxicological evaluation of Forsythia suspensa leaves tea

Da-Hong Wang,Meng-Yang Wang,Wen-Hao Shen,Jiang-Feng Yuan 한국식품과학회 2021 Food Science and Biotechnology Vol.30 No.2

To determine the compositions of Forsythia suspensa leaves tea (FSLT) and its safety, the chemical compounds were analysed with some methods, and the toxicity was evaluated in Kunming mice and Wistar rats. The results showed that FSLT contained rich flavonoid, lignans, triperpene acids, amino acids, and mineral elements. In the acute toxicity study, none of the mice died, and no obvious poisoning symptoms were observed after 14 days in mice at the dose of 15 mg/g·body weight (bw) FSLT; in the sub-chronic toxicity, no abnormal or dead rat was found at the dose of 1, 3, and 10 mg/g·bw during 90 days feeding administration; there was no significant difference in bw and food consumption; no significant differences were found in each hematology and serum biochemistry parameter and organ/body weight ratio comparing with the control experimental group. The results revealed that the FSLT has low or no toxicity via oral administration. Therefore, FSLT is very suitable and safe to be used as a new resource food.

BMB Reports : Dickkopf-1 is involved in BMP9-induced osteoblast differentiation of C3H10T1/2 mesenchymal stem cells

( Liangbo Lin ),( Quanhe Qiu ),( Nian Zhou ),( Wen Dong ),( Jieliang Shen ),( Wei Jiang ),( Ji Fang ),( Jie Hao ),( Zhenming Hu ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.3

Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering. [BMB Reports 2016; 49(3): 179-184]

Self-assembled micelles of the natural medicine ginsenosides for cancer metastasis therapy

Xia-Rong Tan,Chao-Li,Ke-Ke Feng,Jing-Qing Le,Jiang-Wen Shen,Jing-Wei Shao 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.116 No.-

The nanocarrier-based drug delivery systems have become an alternative strategy for cancer treatment. Whereas, increasing studies find that the utilization of drug carriers may result in poor biocompatibility,lower drug loading capacity and unpredictable side reactions. Therefore, we herein reported selfassembledmicelles based on herbal product ginsenosides, which are the main active ingredients ofPanax ginseng C.A. The ginsenosides-based micelle system exerts excellent biosafety, better stability, highdrug capacity, and lower cytotoxicity compared to free ginsenosides. Meanwhile, ginsenosides micellesexhibits superior inhibitory effects on cancer cell adhesion activity, especially the expression of intercellularadhesion molecule-1, which is the critical factor of cancer metastasis. Importantly, ginsenosidesmicelles results in remarkably therapeutic efficacy on lung metastasis of liver cancer. All these resultshighlight the potential utilization of ginsenosides micelles in the clinic. Meanwhile, the carrier-freenano-drugs self-delivery system of ginsenosides showed great promise to become an emerging approachfor cancer metastasis therapy.

Evaluation of Several Screening Approaches for Detection of Cervical Lesions in Rural Shandong, China

Zong, Li-Ju,Zhang, You-Zhong,Yang, Xing-sheng,Jiang, Jie,Cui, Bao-Xia,Qiao, Yun-Bo,Li, Li,Jiang, Kan,Zhang, Wen-Jing,Kong, Bei-Hua,Shen, Keng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Purpose: The study was designed to: (1) investigate the prevalence of high-risk human papillomavirus (HR-HPV) infection and cervical neoplasia; and (2) evaluate clinical performance of visual inspection with acetic acid/ Lugol's iodine (VIA /VILI), Pap smear, high-risk human papillomavirus (HR-HPV) DNA test for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and (3) explore appropriate screening approach in rural areas of Shandong Province. Materials and Methods: A total of 3,763 eligible women from Yiyuan County in Yimeng mountainous areas of rural Shandong, China, were enrolled and underwent Pap smear, HR-HPV DNA testing by Hybrid Capture 2 (HC2), and VIA /VILI tests. Women positive in any test were referred to colposcopy and biopsy as indicated. Results: The prevalence of HR-HPV infection among all enrolled women was 11.1% and that in healthy women was 9.9%. In total 33 cases of CIN1, 16 cases of CIN2, 6 cases of CIN3 but none of cervical cancer were detected and the crude prevalence of CIN2+ was 0.58%. For detecting CIN2+, the sensitivity of HR-HPV DNA testing, VIA/VILI, Pap smear was 90.9%, 77.3%, 81.8%, respectively. Pap smear had the best specificity of 98.2%, followed by HR-HPV DNA testing with specificity of 89.4%, VIA/VILI had the lowest specificity of 81.2%. Colposcopy referral rate of HR-HPV DNA testing, VIA/VILI, Pap smear was 11.1%, 18.5%, 2.3%, respectively. Conclusions: Our results suggest that HR-HPV DNA testing alone might be appropriate for primary cervical cancer screening in rural low-resource areas of Shandong Province, China.