Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Functionalized liposomes can improve the in vivo process of drugs to achieve high-efficiency delivery by enhancing drug absorption， changing drug distribution and reducing the elimination， which is one of the hotspots in nanomedicine research with broad application prospects. However， the drug information published by official websites of National Medical Products Administration （NMPA）， the United States Food and Drug Administration （FDA）， and the European Medicines Agency （EMA） shows that there are few liposomal products on the market， and the domestic varieties are mainly generic drugs. Excepting for polyethylene glycolized （PEGylated） liposomes， no other functionalized liposomes have been approved for marketing， which indicates that the clinical translation of functionalized liposomes remains at a low level. Therefore， the relevant reports of functionalized liposomes in recent years were reviewed in this paper， their application advantages and main challenges in preparation research and development were discussed based on the in vivo process， and their low clinical translation mainly because of the insufficient clinical thinking， safety and efficacy of functional materials， inaccurate in vitro and in vivo analysis methods and difficulty in scaling up production. Meanwhile， the possible strategies such as introducing the concept of clinical multi-function to improve clinical acuity， focusing on examining the modification density of functional materials and the interaction between the modified materials， evaluating the drug delivery performance of functionalized liposomes from multiple perspectives and scenarios， and conducting cost and convenience-oriented formulation composition and preparation process optimization were proposed in order to provide a reference for the development of functionalized liposomes and other carrier-based nanomedicines.

Bone is a connective tissue that has important functions in the human body. Cells and the extracellular matrix (ECM) are key components of bone and are closely related to bone-related diseases. However, the outcomes of conventional treatments for bone-related diseases are not promising, and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy. Circular RNAs (circRNAs) are single-stranded RNAs that form closed circular structures without a 5' cap or 3' tail and polycyclic adenylate tails. Due to their high stability, circRNAs have the potential to be typical biomarkers. Accumulating evidence suggests that circRNAs are involved in bone-related diseases, including osteoarthritis, osteoporosis, osteosarcoma, multiple myeloma, intervertebral disc degeneration, and rheumatoid arthritis. Herein, we summarize the recent research progress on the characteristics and functions of circRNAs, and highlight the regulatory mechanism of circRNAs in bone-related diseases.
Humans ; RNA, Circular ; RNA ; Biomarkers ; Osteoarthritis

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its “pharmacodynamic group”. By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the “pharmacodynamic group” for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and “pharmacodynamic group”, it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and “pharmacodynamic group” in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and “pharmacodynamic group”.

OBJECTIVE: To determine the correlation of phosphorylated ribosomal S6 protein (P-S6) content in blood and brain tissue in mice and rats with seizure. METHODS: Seizure models were induced by intraperitoric injection of kainic acid (KA) in C57BL/mice and SD rats. Flow cytometry was used to detect the content of P-S6 in blood; Western blot was used to detect the expression of P-S6 in brain tissues. The correlation between P-S6 expression in blood and in brain tissue was examine by Pearson analysis, and the correlation between P-S6 expression in blood and the severity of seizure was also observed. RESULTS: Western blotting analysis showed that the expression of P-S6 was significantly increased in peripheral blood and brain tissue in mice 1 h after KA-induced seizure,and the expression levels increased to (1.49±0.45) times (<0.05) and (2.55±0.66) times ( <0.01) of the control group, respectively. Flow cytometry showed that the positive percentage and average fluorescence intensity of P-S6 in the blood of mice increased significantly 1 h after KA-induced seizures (<0.01), which was consistent with the expression of P-S6 in brain tissue (=0.8474, <0.01). Flow cytometry showed that the average fluorescence intensity of P-S6 in blood increased from 14.89±9.75 to 52.35±21.72 (<0.01) in rats with seizure, which was consistent with the change of P-S6 in brain tissue (=0.9385, <0.01). Rats with higher levels of seizure were of higher levels of P-S6 in peripheral blood. CONCLUSIONS Consistent correlation of P-S6 expression is demonstrated in peripheral blood and in brain tissue after KA-induced seizure, suggesting that the expression of P-S6 in blood can accurately reflect the changes of mTOR signaling pathway in brain tissue.
Animals ; Brain ; drug effects ; physiopathology ; Gene Expression Regulation ; drug effects ; Kainic Acid ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Seizures ; blood ; chemically induced ; physiopathology

Objective To evaluate the outcome of combination of intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia (ALL). Methods Between 2009 and 2010, 8 patients diagnosed as Ph+ ALL received allo-HSCT from HLA identical sibling during complete remission. Imatinib was added into the therapies of 5 patients.Seven patients received the intensive preconditioning regimen based on BuCy2, one patient received the regimen of TBI-Cy. A median of 6. 02 × 108/kg mononuclear cells and 3. 14 × 106/kg CD34+ cells were transfused. GVHD prophylaxis included cyclosporine A and methotrexate. Results All patients were well tolerant to the regimen without serious regimen-related toxicity. The median time of ANC≥0. 5 × 109/L was 15. 5 days, and that of PLT≥20 × 109/L was 19 days. Thirty days after allo-HSCT, all patients got donor engraftment successfully. Among 8 cases, 4 cases presented acute GVHD, 2 developed degree Ⅰ , one developed degree Ⅱ , and one developed degree Ⅳ. Seven patients were alive 100 days after allo-HSCT, 3 of whom presented chronic GVHD. At the end of following-up period, 6 patients were alive, among them, 3 patients were alive without relapse; 3 patients relapsed; Two patients died, one from acute GVHD, and one from leukemia relapse. Conclusion Combined intensive preconditioning regimen allo-HSCT with Imatinib was an effective treatment for Ph+ ALL, but the effect of anti-chronic GVHD of imatinib should arouse certain attention.

Objective To retrospectively analyze and compare the curative outcome of hematopoietic stem cell transplantation (HSCT) from HLA identical siblings vs intensive immunosuppression therapy (IST) for severe aplastic anemia (SAA).Methods From January 2008 to December 2010,41 patients with severe aplastic anemia were treated with related HSCT (n =14) or IST (n =27) which combined antithymocyte globulin (ATG) with cyclosporine-A (CsA) therapy.Results All the patients receiving HSCT reached complete response.Among the patients receiving IST,21 patients could be responsive to the therapy,and 2 patients died.There was significant difference in the response rate between HSCT group and IST group (100 ％ vs 77.8 ％,P＜0.01 ).Conclusion With the improvement of HSCT technology,the curative outcome of HSCT from HLA identical siblings for SAA is much better than IST.

Objective To analyze the outcome of idarubicin-intensified myeloablastive conditioning regimen in allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in patients with myelodysplastic syndromes (MDS). Methods From August 2004 to July 2009, 12 patients with MDS were treated with alIo-PBSCT following the idarubicin-intensified conditioning regimen. The conditioning regimen was idarubicin (15 mg/m~2), continuous intravenous infusion for 20 h, days-12 to-10; busulfan (0.8 mg/kg), intravenous infusion every 6 h, days-6 to-4; cyclophosphamide (1.8 g/m~2), intravenous infusion every 6 h, days-3 to-2; cyclosporine A combined with short-term methotrexate was used for the prophylaxes of acute graft versus host disease (aGVHD). Results All twelve patients achieved Trilineage engraftment, and were well tolerated to this regimen. Eight patients survived, and the overall survival was 66.7%, disease-free survival (DFS) 58.3%. Two patients relapsed. OS for neither WHO subgroups nor IPSS subgroups had statistically significant difference. Conclusion Allo-PBSCT with idarubicin-inteusified conditioning regimen is an effective treatment with reduction of the relapse rate for MDS patients.

This study examined the expressions of human serum tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their clinical significance. The serum TFand TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplantation and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipients in the absence of aGVHD or with grade Ⅰ aGVHD before and after the transplantation. The levels of serum TF and TFPI were substantially increased in the patients with grade Ⅱ aGVHD at the peak of aGVHD (P＜0.05) and they were even higher in the patients with grade Ⅲ-Ⅳ aGVHD (P＜0.01). When the conditions became stable after treatment with immunosuppressive agents,the serum TFPI level was decreased to the baseline level (P＞0.05) and the TF level was lowered but still higher than the baseline level (P＜0.05). It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade Ⅱ-Ⅳ aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence,outcome and prognosis of aGVHD.