Potential biomarkers for the early detection of bone metastases.

The clinical manifestations of bone metastases are diversified while many sites remain asymptomatic at early stage. As the early diagnosis method is not perfect and the early symptoms of tumor bone metastasis are not typical, bone metastasis is not easy to be detected. Therefore, the search for bone metastasis-related markers is effective for timely detection of tumor bone metastases and the development of drugs to inhibit bone metastases. As a result, bone metastases can only be diagnosed when symptoms are found, increasing the risk of developing skeletal-related event (SREs), which significantly impairs the patient's quality of life. Therefore, the early diagnosis of bone metastases is of great importance for the treatment and prognosis of cancer patients. Changes of bone metabolism indexes appear earlier in bone metastases, but the traditional biochemical indexes of bone metabolism lack of specificity and could be interfered by many factors, which limits their application in the study of bone metastases. Some new biomarkers of bone metastases have good diagnostic value, such as proteins, ncRNAs, circulating tumor cells (CTCs). Therefore, this study mainly reviewed the initial diagnostic biomarkers of bone metastases which were expected to provide references for the early detection of bone metastases.

Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan Isolate Streptomyces sp. PU-MM59.

Himalaquinones A-G, seven new anthraquinone-derived metabolites, were obtained from the Himalayan-based Streptomyces sp. PU-MM59. The chemical structures of the new compounds were identified based on cumulative analyses of HRESIMS and NMR spectra. Himalaquinones A-F were determined to be unique anthraquinones that contained unusual C-4a 3-methylbut-3-enoic acid aromatic substitutions, while himalaquinone G was identified as a new 5,6-dihydrodiol-bearing angucyclinone. Comparative bioactivity assessment (antimicrobial, cancer cell line cytotoxicity, impact on 4E-BP1 phosphorylation, and effect on axolotl embryo tail regeneration) revealed cytotoxic landomycin and saquayamycin analogues to inhibit 4E-BP1p and inhibit regeneration. In contrast, himalaquinone G, while also cytotoxic and a regeneration inhibitor, did not affect 4E-BP1p status at the doses tested. As such, this work implicates a unique mechanism for himalaquinone G and possibly other 5,6-dihydrodiol-bearing angucyclinones.

Tumor Noninvasive and Target Embolization Therapy Platform by Intravenous Injection Based on Acidic Microenvironment-Responsive Hyperbranched Poly(amino acid)s.

Transcatheter arterial embolization (TAE) has been widely applied in treatments of unresectable or hypervascular tumors, but the procedure of TAE is complicated possibly brings inherent risks. Here, inspired by pH-responsive drug delivery systems, a new method of noninvasive and target embolization therapy by intravenous injection was developed. This method is based on a type of acidic microenvironment-responsive hyperbranched poly(amino acid) (HPTTG) to avoid using catheterization and real-time image guidance angiography, simplifying the procedure, elevating compliance and general applicability of embolization therapy. The pH value of the sol-to-gel phase transition with decreasing pH of HPTTG was controlled by adjusting the ratio of acidic amino acids in copolymers. The results of the tumor-bearing animal experiment indicate that the HPTTG have an excellent target and embolic ability; they accumulate the most at the tumor site in 8 h postinjection. Blood vessels of the tumors were occluded, and the tumors were inhibited and necrotized in about 20 days. Therefore, it is expected that HPTTG not only can be used as novel embolic materials for efficient noninvasive embolization therapy of many solid tumors but also can be used as a multifunctional platform for combined theranostics, for example, combination with controlled release, thermal ablation, multimodal imaging, synergistic therapy, etc.

All-in-one hyperbranched polypeptides for surgical adhesives and interventional embolization of tumors.

A series of hyperbranched, thermo-responsive and mussel-inspired polypeptides were synthesized and used for surgical adhesion, hemostasis and interventional embolization. These polypeptides showed excellent tissue-adhesive properties according to adhesive strength tests on porcine skin and bone in vitro, where the maximum lap-shear adhesion strength on porcine skin was 114.5 kPa and the maximum tensile adhesion strength on bone was 786 kPa. In vivo animal experiments indicated that these polypeptides exhibit superior hemostatic properties and healing effects in skin incisions and osteotomy gap; the skin incision healing and osteotomy gap remodeling were completed in all rats after 14 and 60 days, respectively. In vivo evaluation of the embolization ability of these polypeptides was performed on rabbit kidney models, resulting in successful occlusion of renal arteries, which led to gross ischemic changes in the embolized kidneys up to 16 days. A trial embolization procedure on H22 tumor-bearing rat models also confirmed the gelability of these polypeptides in tumor arteries, which might cause damage to embolized tumors. Therefore, these polypeptides are expected to be good candidates as surgical tissue adhesives, antibleeding materials, and effective embolic materials.

Evaluation of hepatocyteprotective and anti-hepatitis B virus properties of Cichoric acid from Cichorium intybus leaves in cell culture.

Hepatitis B is the most common serious liver infection in the world. To date, there is still no complete cure for chronic hepatitis B. Natural caffeic acid analogues possess prominent antiviral activity, especially anti-hepatitis B virus (HBV) and anti-human immunodeficiency virus effects. Cichoric acid is a caffeic acid derivative from Cichorium intybus. In the study, the anti-hepatitis B property of cichoric acid was evaluated by the D-galactosamine (D-GalN)-induced normal human HL-7702 hepatocyte injury model, the duck hepatitis B virus (DHBV)-infected duck fetal hepatocytes and the HBV-transfected cell line HepG2.2.15 cells, respectively. The results showed that cichoric acid attenuated significantly D-GalN-induced HL-7702 hepatocyte injury at 10-100 µg/mL and produced a maximum protection rate of 56.26%. Moreover, cichoric acid at 1-100 µg/mL inhibited markedly DHBV DNA replication in infected duck fetal hepatocytes. Also, cichoric acid at 10-100 µg/mL reduced significantly the hepatitis B surface and envelope antigen levels in HepG2.2.15 cells and produced the maximum inhibition rates of 79.94% and 76.41%, respectively. Meanwhile, test compound at 50-100 µg/mL inhibited markedly HBV DNA replication. In conclusion, this study verifies the anti-hepatitis B effect of cichoric acid from Cichorium intybus leaves. In addition, cichoric acid could be used to design the antiviral agents.

Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells.

In order to validate the antiviral effect against hepatitis B virus (HBV) of Taraxacum mongolicum (T. mongolicum), the protective effect on hepatocytes, and antiviral properties against duck hepatitis B virus (DHBV) and HBV of T. mongolicum extract (TME) were evaluated in chemically-injured neonatal rat hepatocytes, DHBV-infected duck fetal hepatocytes and HBV-transfected HepG2.2.15 cells, respectively. The results demonstrated that TME at 50-100 µg/ml improved D-galactosamine (D-GalN), thioacetamide (TAA) and tert-butyl hydroperoxide (t-BHP)-injured rat hepatocytes, and produced protection rates of 42.2, 34.6 and 43.8% at 100 µg/ml, respectively. Furthermore, TME at 1-100 µg/ml markedly inhibited DHBV DNA replication. Additionally, TME at 25-100 µg/ml reduced HBsAg and HBeAg levels and produced inhibition rates of 91.39 and 91.72% at 100 µg/ml, respectively. TME markedly inhibited HBV DNA replication at 25-100 µg/ml. The results demonstrate the potent antiviral effect of T. mongolicum against HBV effect. The protective of TME effect on hepatocytes may be achieved by its ability to ameliorate oxidative stress. The antiviral properties of TME may contribute to blocking protein synthesis steps and DNA replication. Furthermore, major components of TME were quantificationally analyzed. These data provide scientific evidence supporting the traditional use of TME in the treatment of hepatitis.

Chromosome dynamic changes in two cultured Chinese human embryonic stem cell lines: single nucleotide polymorphism, copy number variation and loss of heterozygosity.

The quality and safety of human embryonic stem cells (hESCs) in clinical application depend on gene stability. Two Chinese hESC lines, Zh1 and Zh21, were incubated over a long period. We observed and compared the gene stability in the passage numbers 20, 17 for Zh1 cell line and passage numbers 27, 60, 68 for Zh21 cell line. Single nucleotide polymorphisis analysis indicated that hESCs in early passages had relative gene stability; and with the increase in passage number, gene instability became strong. We also found that there were copy number variations (CNVs) in both Zh21 and Zh1. We analyzed the CNVs of Chinese Han Beijing man (CHB; normal Chinese people) and found that the all CNV forms were the loss in Zh21, Zh1, and CHB. We also analyzed and compared the related pathways of the mutant genes. We propose three steps to ensure hESC safety. Firstly, besides the conventional methods such as pluripotent genes, chromosome G-banding and teratoma, high-resolution DNA chip analysis should also be adopted; secondly, chromosomal properties are monitored every 10 passages in less than passage 50 and every 5 passages in more than passage 50; thirdly, the related pathways of mutant genes should be observed because only the mutant genes with variations of their related pathways may affected cell functions.

Two new iridoid glucosides from Hedyotis diffusa.

Two new iridoid glucosides, named diffusosides A and B, were isolated from the aerial part of Hedyotis diffusa Willd. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis and HRESIMS. These two compounds showed no cytotoxic activity against SMMC-7721, SW480, SW620, Bel7402, and HepG2 cells.

[Analysis of the chemical constituents of Hedyotis diffusa].

OBJECTIVE: To analyze the chemical constituents of Hedyotis diffusa. METHODS: Column chromatographies were used to isolate and purify the chemical constituents of this plant, and their structures were identified by spectral analysis and physicochemical properties. RESULTS AND CONCLUSION: Seven compounds were isolated and identified as p-coumaric acid (I), methyl-p-coumarate (II), 2-formyl-5- hydroxymethylfuran (III), quercetin (IV), kaempferol (V), beta-sitosterol(VI) and daucosterol(VII), respectively, among which the compounds II and III were isolated from Hedyotis diffusa for the first time.