Cell migration plays a critical role in vascular homeostasis. Under noxious stimuli, endothelial cells (ECs) migration always contributes to vascular repair, while enhanced migration of vascular smooth muscle cells (VSMCs) will lead to pathological vascular remodeling. Moreover, vascular activities are involved in communication between ECs and VSMCs, between ECs and immune cells, et al. Recently, Ma et al. (2015) discovered a novel migration-dependent organelle “migrasome,” which mediated release of cytoplasmic contents, and this process was defined as “migracytosis.” The formation of migrasome is precisely regulated by tetraspanins (TSPANs), cholesterol and integrins. Migrasomes can be taken up by neighboring cells, and migrasomes are distributed in many kinds of cells and tissues, such as in blood vessel, human serum, and in ischemic brain of human and mouse. In addition, the migrasome elements TSPANs are wildly expressed in cardiovascular system. Therefore, TSPANs, migrasomes and migracytosis might play essential roles in regulating vascular homeostasis. In this review, we will discuss the discoveries of migration-dependent migrasome and migracytosis, migrasome formation, the basic differences between migrasomes and exosomes, the distributions and functions of migrasome, the functions of migrasome elements TSPANs in vascular biology, and discuss the possible roles of migrasomes and migracytosis in vascular homeostasis.

Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

In this work, a label-free DNAzyme biosensor was proposed for the detection of oligonucleotides related to a hepatitis B virus (HBV) DNA segment. The novel DNAzyme biosensor was based on the electrochemical reduction of graphene oxide–carboxyl multi-walled carbon nanotube composites (GO–CMWCNTs) and the electrodeposition of gold nanoparticles (AuNPs) on a glassy carbon electrode (GCE). The thiolate hairpin capture probes with a caged G-quadruplex configuration were self-assembled on AuNPs through the well-known Au–thiol binding. Only after hybridization with target DNA, the hairpin configuration could be opened and released the particular guanine-rich nucleic acid sequences which could assemble to G-quadruplexes. In the presence of hemin and K⁺, the hemin/G-quadruplex DNAzyme was generated on the electrode surface, triggering the electrochemical H₂O₂-mediated oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). With the advantages of amplification effects of AuNPs and hemin/G-quadruplex, a linear concentration range from 10 pM to 10 nM with a limit of detection of 0.5 pM was obtained for the target DNA. This method exhibited excellent discrimination of target DNA from one or two-base mismatched DNA and non-complementary DNA sequences. In addition, the proposed biosensor was successfully applied to the determination of target DNA in human serum samples.

Tanshinone I (Tan-I) is a diterpene quinone extracted from the traditional herbal medicine Salvia miltiorrhiza Bunge . Recently, Tan-I has been reported to have anti-tumor effects. In this study, we investigated the growth inhibition and apoptosis inducing effects of Tan-I on three kinds of monocytic leukemia cells (U937, THP-1 and SHI 1). Cell viability was measured by MTT assay. Cell apoptosis was assessed by flow cytometry (FCM) and AnnexinV/PI staining. Reverse transcriptase polymerase chain reaction (RT-PCR) and PCR–enzyme-linked immunosorbent assay (ELISA) were used to detect human telomerase reverse transcriptase (hTERT) expression and telomerase activity before and after apoptosis.The activity of caspase-3 was determined by Caspase colorimetric assay kit and Western blot analysis. Expression of the anti-apoptotic gene Survivin was assayed by Western blot and Real-time RT-PCR using the ABI PRISM 7500 Sequence Detection System. The resultsrevealed that Tan-I could inhibit the growth of these three kinds of leukemia cells and cause apoptosis in a time- and dose-dependent manner. After treatment by Tan-I for 48 h, Western blotting showed cleavage of the caspase-3 zymogen protein with the appearance of its 17-kD subunit, and a 89-kD cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also found clearly. The expression of hTERT mRNA as well as activity of telomerase were decreased concurrently in a dose-dependent manner. Moreover, Real-time RT-PCR and Western blot revealed a significant down-regulation of Survivin. We therefore conclude that the induction of apoptosis by Tan-I in monocytic leukemia U937 THP-1 and SHI 1 cells is highly correlated with activation of caspase-3 and decreasing of hTERT mRNA expression and telomerase activity as well as down-regulation of Survivin expression. To our knowledge, this is the first report about the effects of Tan-I on monocytic leukemia cells.

Diethylnitrosamine (DEN) is present in food, water, and daily supplies and is regarded as a toxicant of carcinogenicity. The developmental toxicity of DEN has been rarely reported as yet. In this study, zebrafish were exposed to different concentrations of DEN at 6 h post-fertilization (hpf) to access embryonic toxicity of the compound. The results show that DEN resulted in negative effects of hatching rate, heartbeat, body length, and spontaneous movement. Deformities, including notochord malformation, pericardium edema, embryonic membrane turbidity, tail hypoplasia, yolk sac deformity, and growth retardation, happened during exposure period. Moreover, production of reactive oxygen species (ROS) significantly increased after DEN treatment. Then, alterations of the expression level of oxidative stress-related genes were observed in our results. To our knowledge, this is the first study concerning the effect of DEN on zebrafish. And from the information of our research, we speculated that development toxicity of DEN should be related to the excessive oxidative stress.

Basic and clinical studies have shown that hydrogen (H₂), the lightest gas in the air, has significant biological effects of anti-oxidation, anti-inflammation, and anti-apoptosis. The mammalian cells have no abilities to produce H₂ due to lack of the expression of hydrogenase. The endogenous H₂ in human body is mainly produced by anaerobic bacteria, such as Firmicutes and Bacteroides, in gut and other organs through the reversible oxidation reaction of 2 H⁺ + 2 e^- ⇌ H₂. Supplement of exogenous H₂ can improve many kinds of liver injuries, modulate glucose and lipids metabolism in animal models or in human beings. Moreover, hepatic glycogen has strong ability to accumulate H₂, thus, among the organs examined, liver has the highest concentration of H₂ after supplement of exogenous H₂ by various strategies in vivo. The inadequate production of endogenous H₂ play essential roles in brain, heart, and liver disorders, while enhanced endogenous H₂ production may improve hepatitis, hepatic ischemia and reperfusion injury, liver regeneration, and hepatic steatosis. Therefore, the endogenous H₂ may play essential roles in maintaining liver homeostasis.