1. E. coli Nissle 1917-Derived Minicells for Targeted Delivery of Chemotherapeutic Drug to Hypoxic Regions for Cancer Therapy
Y Zhang, W Ji, L He, Y Chen, X Ding, Y Sun, S Hu
Theranostics. 2018; 8(6): 1690–1705
Systemic administration of free chemotherapeutic drugs leads to severe toxic effects, and physiological characteristics of solid tumors restrain the drugs from reaching the hypoxic regions. E. coli Nissle 1917 (EcN) has been known to penetrate the barrier and proliferate in the interface between the viable and necrotic regions of tumors. This study aimed to fabricate a nanoscale minicell via genetic engineering of EcN for targeted delivery of chemotherapeutic drugs to the hypoxic regions of tumors for cancer therapy.
產品：anti-6×His rabbit polyclonal antibody(D110002); FITC-conjugated anti-rabbit antibody(D110051)
2. Maintaining the pluripotency of mouse embryonic stem cells on gold nanoparticle layers with nanoscale but not microscale surface roughness
Z Lyu, H Wang, Y Wang, K Ding, H Liu, L Yuan, X Shi
Nanoscale. 2014; 6, 6959-6969
Efficient control of the self-renewal and pluripotency maintenance of embryonic stem cell (ESC) is a prerequisite for translating stem cell technologies to clinical applications. Surface topography is one of the most important factors that regulates cell behaviors. In the present study, micro/nano topographical structures composed of a gold nanoparticle layer (GNPL) with nano-, sub-micro-, and microscale surface roughnesses were used to study the roles of these structures in regulating the behaviors of mouse ESCs (mESCs) under feeder-free conditions. The distinctive results from Oct-4 immunofluorescence staining and quantitative real-time polymerase chain reaction (qPCR) demonstrate that nanoscale and low sub-microscale surface roughnesses (Rq less than 392 nm) are conducive to the long-term maintenance of mESC pluripotency, while high sub-microscale and microscale surface roughnesses (Rq greater than 573 nm) result in a significant loss of mESC pluripotency and a faster undirectional differentiation, particularly in long-term culture. Moreover, the likely signalling cascades engaged in the topological sensing of mESCs were investigated and their role in affecting the maintenance of the long-term cell pluripotency was discussed by analyzing the expression of proteins related to E-cadherin mediated cell–cell adhesions and integrin-mediated focal adhesions (FAs). Additionally, the conclusions from MTT, cell morphology staining and alkaline phosphatase (ALP) activity assays show that the surface roughness can provide a potent regulatory signal for various mESC behaviors, including cell attachment, proliferation and osteoinduction.
產品：primary antibodies Oct-4(D121072)
3. Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α
W Wan, K Peng, M Li, L Qin, Z Tong, J Yan, B Shen
Oncogene.2017; 36, 3868–3877
High aerobic glycolysis not only provides energy to cancer cells, but also supports their anabolic growth. JMJD1A, a histone demethylase that specifically demethylates H3K9me1/2, is overexpressed in multiple cancers, including urinary bladder cancer (UBC). It is unclear whether JMJD1A could promote cancer cell growth through enhancing glycolysis. In this study, we found that downregulation of JMJD1A decreased UBC cell proliferation, colony formation and xenograft tumor growth. Knockdown of JMJD1A inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4. Mechanistically, JMJD1A cooperated with hypoxia inducible factor 1α (HIF1α), an important transcription factor for glucose metabolism, to induce the glycolytic gene expression. JMJD1A was recruited to the promoter of glycolytic gene PGK1 to demethylate H3K9me2. However, the JMJD1A (H1120Y) mutant, which loses the demethylase activity, failed to cooperate with HIF1α to induce the glycolytic gene expression, and failed to demethylate H3K9me2 on PGK1 promoter, suggesting that the demethylase activity of JMJD1A is essential for its coactivation function for HIF1α. Inhibition of glycolysis through knocking down HIF1α or PGK1 decelerated JMJD1A-enhanced UBC cell growth. Consistent with these results, a positive correlation between JMJD1A and several key glycolytic genes in human UBC samples was established by analyzing a microarray-based gene expression profile. In conclusion, our study demonstrates that JMJD1A promotes UBC progression by enhancing glycolysis through coactivation of HIF1α, implicating that JMJD1A is a potential molecular target for UBC treatment.
4. Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway
X Xie, Y Zhao, CY Ma, XM Xu, YQ Zhang
British Journal of Pharmacology. 2015; 172, 3929–3943
Dimethyl fumarate (DMF) is a newly approved drug for the treatment of relapsing forms of multiple sclerosis and relapsing‐remitting multiple sclerosis. Here, we investigated the effects of DMF and its metabolites mono‐methylfumarate (MMF and methanol) on different gastrointestinal cancer cell lines and the underlying molecular mechanisms involved.
產品：Anti-bax(D120073); Anti-bcl-2(D260117); Anti-gapdh(D110016); Anti-actin antibodies(D110001)
5. Dietary leucine supplementation alters energy metabolism and induces slow-to-fast transitions in longissimus dorsi muscle of weanling piglets
Q Fan, B Long, G Yan, Z Wang, M Shi, X Bao
Br J Nutr. 2017 May;117(9):1222-1234
Leucine plays an important role in promoting muscle protein synthesis and muscle remodelling. However, what percentage of leucine is appropriate in creep feed and what proteome profile alterations are caused by dietary leucine in the skeletal muscle of piglets remain elusive. In this case, we applied isobaric tags for relative and absolute quantitation to analyse the proteome profile of the longissimus dorsi muscles of weanling piglets fed a normal leucine diet (NL; 1·66 % leucine) and a high-leucine diet (HL; 2·1 % leucine). We identified 157 differentially expressed proteins between these two groups. Bioinformatics analysis of these proteins exhibited the suppression of oxidative phosphorylation and fatty acid β-oxidation, as well as the activation of glycolysis, in the HL group. For further confirmation, we identified that SDHB, ATP5F1, ACADM and HADHB were significantly down-regulated (P<0·01, except ATP5F1, P<0·05), whereas the glycolytic enzyme pyruvate kinase was significantly up-regulated (P<0·05) in the HL group. We also show that enhanced muscle protein synthesis and the transition from slow-to-fast fibres are altered by leucine. Together, these results indicate that leucine may alter energy metabolism and promote slow-to-fast transitions in the skeletal muscle of weanling piglets.
產品：pyruvate kinase (PKM) (D120008); succinate dehydrogenase SDHB(D162175)
6. Mass-production of fluorescent chitosan/graphene oxide hybrid microspheres for in vitro 3D expansion of human umbilical cord mesenchymal stem cells
S Zhang, B Ma, S Wang, J Duan, J Qiu, D Li Fan, B Long, G Yan, Z Wang, M Shi, X Bao
Chemical Engineering Journal. 2018; 331, 675-684
In this work, we designed a simple and low cost acid-dissolved/alkali-solidified self-sphering shaping method (AASS) to automatically fabricate three-dimension (3D) stem cell expansion microsphere scaffolds in large scale to satisfy the urgent need for stem cells in tissue engineering and clinical medicine research. We chose chitosan as the main part of microsphere scaffold, graphene oxide of 3 wt% as the strength agent, and genipin as the fluorescence generator to fabricate fluorescent chitosan (CS)/graphene oxide (GO) hybrid microspheres. The diameters of the hybrid microspheres are about 400 μm with the diameter error less than 10%, which is suitable for stem cells spreading. These hybrid microspheres with good biocompatibility can support the cells’ spread, growth and proliferation. After cultured for 5 days, the total number of cells on microspheres has almost increased fourfold. Most importantly, the microspheres can maintain the cell type. After cultured for 7 days, almost all cells still express main markers of human umbilical cord mesenchymal stem cells (HUMSCs). The hybrid microspheres can support long-time stem cell expansion because of their good mechanical strength, controllable degradability, and low expansion rate when soaked in media. Furthermore, their autofluorescence also makes observing and tracking the stem cells behavior on surface of microsphere scaffolds more convenient. This research provides a powerful method for mass-producing chitosan/graphene oxide hybrid microspheres for 3D stem cells expansion. This method is easy to be put into industrial production, and may have tremendous value in medicinal and clinical applications.
產品：CD29 and CD44 antibody (D120869; D122619)
7. Interaction of WBP2 with ERα increases doxorubicin resistance of breast cancer cells by modulating MDR1 transcription
S Chen, H Wang, Z Li, J You, QW Wu, C Zhao
British Journal of Cancer volume. 2018; 119, 182–192
Surgery combined with new adjuvant chemotherapy is the primary treatment for early stage invasive and advanced stage breast cancer. Growing evidence indicates that patients with ERα-positive breast cancer show poor response to chemotherapeutics. However, ERα-mediated drug-resistant mechanisms remain unclear.
8. Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity
L Cheng, M Ge, Z Lan, Z Ma, W Chi, W Kuang
Archives of Toxicology. 2018; 92,469–485
Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. In this report, human proximal tubular HK-2 cells and mouse models were combined to dissect the molecular pathways underlying nephropathy caused by zoledronate treatments. Metabolomic and proteomic assays revealed that multiple cellular processes were significantly disrupted, including the TGFβ pathway, fatty acid metabolism and small GTPase signaling in zoledronate-treated HK-2 cells (50 μM) as compared with those in controls. Zoledronate treatments in cells (50 μM) and mice (3 mg/kg) increased TGFβ/Smad3 pathway activation to induce fibrosis and kidney injury, and specifically elevated lipid accumulation and expression of fibrotic proteins. Conversely, fatty acid transport protein Slc27a2 deficiency or co-administration of PPARA agonist fenofibrate (20 mg/kg) prevented zoledronate-induced lipid accumulation and kidney fibrosis in mice, indicating that over-expression of fatty acid transporter SLC27A2 and defective fatty acid β-oxidation following zoledronate treatments were significant factors contributing to its nephrotoxicity. These pharmacological and genetic studies provide an important mechanistic insight into zoledronate-associated kidney toxicity that will aid in development of therapeutic prevention and treatment options for this nephropathy.