Non-Benzoquinone Geldanamycin Analog, WK-88-1, Induces Apoptosis in Human Breast Cancer Cell Lines

( Yu-ru Zhao ),( Hong-mei Li ),( Meilin Zhu ),( Jing Li ),( Tao Ma ),( Qiang Huo ),( Young-soo Hong ),( Cheng-zhu Wu ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.4

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88- 1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to G2/M cell cycle arrest. Further studies also showed that WK- 88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and ER-α in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.

Polyvinylchloride Ultrafiltration Membranes Modified with Different SiO2 Particles and Their Antifouling Mechanism for Oil Extraction Wastewater

Zhao, Fang-Bo,Yu, Zhen-Jiang,Park, Hee-Deung,Liu, Xu-Yang,Song, Xiang-Ru,Li, Zhan-Shuang American Society of Civil Engineers 2015 Journal of environmental engineering Vol.141 No.8

Degradation of Lignocelluloses in Rice Straw by BMC-9, a Composite Microbial System

( Hongyan Zhao ),( Hai Ru Yu ),( Xu Feng Yuan ),( Ren Zhe Piao ),( Hu Lin Li ),( Xiao Fen Wang ),( Zong Jun Cui ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.5

To evaluate the potential utility of pretreatment of raw biomass with a complex microbial system, we investigated the degradation of rice straw by BMC-9, a lignocellulose decomposition strain obtained from a biogas slurry compost environment. The degradation characteristics and corresponding changes in the bacterial community were assessed. The results showed that rapid degradation occurred from day 0 to day 9, with a peak total biomass bacterium concentration of 3.3 × 10(8) copies/ml on day 1. The pH of the fermentation broth declined initially and then increased, and the mass of rice straw decreased steadily. The highest concentrations of volatile fatty acid contents (0.291 mg/l lactic acid, 0.31 mg/l formic acid, 1.93 mg/l acetic acid, and 0.73 mg/l propionic acid) as well as the highest xylanse activity (1.79 U/ml) and carboxymethyl cellulase activity (0.37 U/ml) occurred on day 9. The greatest diversity among the microbial community also occurred on day 9, with the presence of bacteria belonging to Clostridium sp., Bacillus sp., and Geobacillus sp. Together, our results indicate that BMC-9 has a strong ability to rapidly degrade the lignocelluloses of rice straw under relatively inexpensive conditions, and the optimum fermentation time is 9 days.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis

Yun-Ru Chen,Ruo-Tong Zhao,Yi-Fang Xu,Yin-Jie Ma,Shao-Bo Hu,Xue-Hui Wang,Bing-Bing Fan,Yan-Ji Zhou,Yu-Bei Huang,Nicola Robinson,Jian-ping Liu,Zhao-Lan Liu 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.4

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21–1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20–2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16–1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

Biosynthesis of rare 20(R)-protopanaxadiol/protopanaxatriol type ginsenosides through Escherichia coli engineered with uridine diphosphate glycosyltransferase genes

Lu Yu,Yuan Chen,Jie Shi,Ru-Feng Wang,Ying-Bo Yang,Li Yang,Shujuan Zhao,Zheng-Tao Wang 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.1

Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes. Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes. Results: E. coli engineered with GT95syn selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3eOH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing p2GT95synK1, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20eOH and C3eOH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth. Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.

Carrier Phase Difference Positioning with Kalman Filter

Xiao-dong Su,Yu-ru Zhang,Hai-tao Jiang,Ming Zhao,Jun-ling Li 보안공학연구지원센터(IJSIP) 2014 International Journal of Signal Processing, Image Vol.7 No.3

Chinese patent herbal medicine (Shufeng Jiedu capsule) for acute upper respiratory tract infections: A systematic review and meta-analysis

Ying-ying Zhang,Ru-yu Xia,Shi-bing Liang,Xiao-yang Hu,Meng-yuan Dai,Yi-lin Li,Le-yi Zhao,Michael Moore,Yu-tong Fei,Jian-ping Liu 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.3

Background: Shufeng Jiedu capsule has been widely used in China for acute upper respiratory tract infections (AURTIs). The aim of this study was to evaluate its effectiveness and safety for AURTIs. Methods: Randomized controlled trials comparing SFJD with conventional drug for patients with AURTIs were included. Eight databases were searched from their inceptions to February 2021. Data was synthesized using risk ration (RR) or mean difference (MD) with their 95% confidence interval (CI). The primary outcome was resolution time of typical symptoms. Results: Twenty-five RCTs involving 3410 patients were included. SFJD in combination with conventional drug was associated with; in common cold shortening the duration of fever (MD −1.54 days, 95% CI [−2.15,−0.92], I2 = 80%, n = 385, 3 trials) and cough (MD −1.22 days, 95% CI [−1.52, −0.93]); in herpangina, shortening the duration of fever (MD -0.68 days, 95% CI [−1.15, −0.21], I2 = 68%, n = 140, 2 trials) and blistering (MD −0.99 days, 95% CI [−1.23, −0.76], n = 386, 3 trials); in acute tonsillitis and acute pharyngitis shortening the duration of fever (MD −1.13 days, 95% CI [−1.36, −0.90], I2 = 33%, n = 688, 7 trials) and sore throat (MD −1.13 days, 95% CI [−1.40, −0.86], I2 = 84.1%, n = 1194, 10 trials). SFJD also improving their cure rate with a range (1–5 days). No serious adverse events were reported. Conclusion: Low certainty evidence suggests that SFJD appears to shorten the duration of symptoms in AURTIs, improve cure rate and seems safe for application. However, high quality placebo controlled trials are warranted to confirm its benefit.

Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells

Ying-ying Xu,Hai-ru Yu,Jia-yi Sun,Zhao Zhao,Shuang Li,Xin-feng Zhang,Zhi-xuan Liao,Ming-ke Cui,Juan Li,Chan Li,Qiang Zhang 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2

Purpose Although the interferon  (IFN) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. Materials and Methods PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. Results PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFN signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFN-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFN-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. Conclusion These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China

Han-Lu Gao,Xuan Wang,Hong-Ru Sun,Jun-De Zhou,Shang-Qun Lin,Yu-Hang Xing,Lin Zhu,Hai-Bo Zhou,Ya-Shuang Zhao,Qiang Chi,Yu-Peng Liu 거트앤리버 소화기연관학회협의회 2018 Gut and Liver Vol.12 No.2

Background/Aims: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. Methods: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. Results: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. Conclusions: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.