Dose- and time-dependent systemic adverse reactions of sodium carboxy methyl cellulose after intraperitoneal application in rats.

Sodium carboxy methyl cellulose (SCMC) is an important absorbable biomaterial for anti-adhesion and hemostasis medical devices used in the abdominal cavity. However, the systemic toxicity of SCMC following intraperitoneal route has not been revealed sufficiently. Three SCMC solutions with gradient concentrations were intraperitoneally injected into 3 groups of rats with the doses of 50 mg/kg, 320 mg/kg and 2000 mg/kg respectively all at once to observe the dose-dependence of systemic reactions of SCMC and 10 rats (5 rats per sex) of each group were sacrificed 3 days, 7 days, 28 days and 90 days after injection to evaluate the time-dependence of the reactions. A range of adverse effects were shown in rats of the high-dose group which were found varied with time extending and virtually disappeared 90 days after injection. Slight reactions were observed in the medium-dose group while negligible effects were found in the low-dose group. The intraperitoneal application of SCMC can induce reversible systemic adverse effects to rats at the dose higher than 320 mg/kg and it is essential to take both dose- and time-dependent effects into account while designing a systemic toxicity study for absorbable biomaterials.

The suitability of reconstructed human epidermis models for medical device irritation assessment: A comparison of In Vitro and In Vivo testing results.

The ISO 10993 standards on biocompatibility assessment of medical devices discourage the use of animal tests when reliable and validated in vitro methods are available. A round robin validation study of in vitro reconstructed human epidermis (RhE) assays was performed as potential replacements for rabbit skin irritation testing. The RhE assays were able to accurately identify strong irritants in dilute medical device extracts. However, there was some uncertainty about whether RhE tissues accurately predicted the results of the rabbit skin patch or intracutaneous irritation test. To address that question, this paper presents in vivo data from the round robin and subsequent follow-up studies. The follow-up studies included simultaneous in vitro RhE model and in vivo testing of round robin polymer samples and the results of dual in vitro/in vivo testing of currently marketed medical device components/materials. Our results show for the first time that for both pure chemicals and medical device extracts the intracutaneous rabbit test is more sensitive to detect irritant activity than the rabbit skin patch test. The studies showed that the RhE models produced results that were essentially equivalent to those from the intracutaneous rabbit skin irritation test. Therefore, it is concluded that RhE in vitro models are acceptable replacements for the in vivo rabbit intracutaneous irritation test for evaluating the irritant potential of medical devices.

A novel method for evaluating the dynamic biocompatibility of degradable biomaterials based on real-time cell analysis.

Degradable biomaterials have emerged as a promising type of medical materials because of their unique advantages of biocompatibility, biodegradability and biosafety. Owing to their bioabsorbable and biocompatible properties, magnesium-based biomaterials are considered as ideal degradable medical implants. However, the rapid corrosion of magnesium-based materials not only limits their clinical application but also necessitates a more specific biological evaluation system and biosafety standard. In this study, extracts of pure Mg and its calcium alloy were prepared using different media based on ISO 10993:12; the Mg2+ concentration and osmolality of each extract were measured. The biocompatibility was investigated using the MTT assay and xCELLigence real-time cell analysis (RTCA). Cytotoxicity tests were conducted with L929, MG-63 and human umbilical vein endothelial cell lines. The results of the RTCA highly matched with those of the MTT assay and revealed the different dynamic modes of the cytotoxic process, which are related to the differences in the tested cell lines, Mg-based materials and dilution rates of extracts. This study provides an insight on the biocompatibility of biodegradable materials from the perspective of cytotoxic dynamics and suggests the applicability of RTCA for the cytotoxic evaluation of degradable biomaterials.

Adaptive Controller Based on Spatial Disturbance Observer in a Microgravity Environment.

In this paper, a new controller for an operating manipulator work in the space microgravity environment is proposed. First, on the basis of the load variation caused by microgravity, a sliding mode control method is used to model the gravity term, and the logistic function is introduced as the approaching function. An improved sliding mode reaching law is proposed to control the manipulator effectively, and Lyapunov theory is used to deduce its closed-loop stability. A friction compensation scheme, which regards friction as disturbance, is introduced to the microgravity environment, and a space disturbance observer (SDO) is designed from the viewpoint of disturbance suppression to identify the friction characteristics of the control system accurately. To model the lagging friction phenomenon caused by velocity inversion during operation tasks, an adaptive compensation scheme based on the LuGre model is proposed. Finally, the design of a manipulator system, which consists of a robot arm, dexterous hand, teleoperation system, central controller, and visual system, is presented. On-orbit maintenance and capture experiments are carried out successively. The effectiveness and reliability of the controller are verified, and the on-orbit operation tasks are completed successfully.

Evaluation of repeated exposure systemic toxicity test of PVC with new plasticizer on rats via dual parenteral routes.

Systemic toxicity caused by repeated exposure to both polar and nonpolar leachables of di(2-ethylhexyl)-1,2-cyclohexane plasticized polyvinyl chloride (PVC) was evaluated with dual routes of parenteral administration method on rats in the study. Experimental group and control group were designed by researchers. Tail intravenous injection with 0.9% sodium chloride injection extracts and intraperitoneal injection with corn oil extracts were conducted to the experimental rats while tail intravenous injection with 0.9% sodium chloride Injection and intraperitoneal injection with corn oil were conducted to the control rats. After 14 days, blood specimens were collected for clinical pathology (hematology and clinical chemistry) analysis. Selected organs were weighed and a histopathological examination was conducted. As a result, compared with the control animals, there were no toxicity-related changes on the parameters above. The results show that the rats do not show obvious systemic toxicity reaction caused by repeated exposure with dual routes of parenteral administration method on rats after administration with both polar and nonpolar exacts of di(2-ethylhexyl)-1,2-cyclohexane plasticized PVC simultaneously up for 14 days.

MicroRNA-34c targets TGFB-induced factor homeobox 2, represses cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma.

MicroRNAs (miRs) are short, non-coding RNAs with post-transcriptional regulatory functions. Previous studies have demonstrated that miR-34c is involved in diverse biological processes, including carcinogenesis. The aim of the present study was to investigate the role of miR-34c and its target genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Expression levels of miR-34c and its predicted target genes were measured. The target genes were validated by a luciferase assay. The effects of miR-34c restoration were evaluated by the detection of HBV antigens, cell proliferation and apoptosis in vitro, in addition to the tumor growth in vivo. The data demonstrated that miR-34c was downregulated in HBV-associated HCC clinical tissues and HCC cell lines compared with their corresponding controls. transforming growth factor-ß-induced factor homeobox 2 (TGIF2), a transcription factor repressing transforming growth factor-ß (TGFß) signaling, was observed to be upregulated and was identified as a target gene of miR-34c. The restoration of miR-34c in HepG2.2.15 cells suppressed TGIF2 expression, HBV replication and viral antigen synthesis; inhibited cell proliferation; and induced apoptosis. miR-34c also inhibited tumor growth in a mouse model. The present study indicates that miR-34c may act as a tumor suppressor by targeting TGIF2 during HBV-associated hepatocellular carcinogenesis. miR-34c and TGIF2 may represent key regulatory factors, diagnostic markers and therapeutic targets for the prevention and treatment of HBV-associated HCC.

miR-122 inhibits viral replication and cell proliferation in hepatitis B virus-related hepatocellular carcinoma and targets NDRG3.

microRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory functions that participate in diverse biological pathways. miR-122, a liver-specific miRNA, has been found to be down-regulated in hepatocellular carcinoma (HCC) and HCC-derived cell lines. In this study, miR-122 was down-regulated in the hepatitis B virus (HBV)-related HCC cell line HepG2.2.15 compared to HepG2. NDRG3, a member of the N-myc downstream-regulated gene (NDRG) family, was up-regulated in HepG2.2.15 and was identified as a target gene of miR-122. An inverse correlation between the expression of miR-122 and the NDRG3 protein was noted in HBV-related HCC specimens. The transfection of the miR-122 expression vector into the HepG2.2.15 cell line repressed the transcription and expression of NDRG3, which subsequently reversed the malignant phenotype of the cells. The replication of HBV, expression of viral antigens and proliferation of cells were significantly inhibited by restoration of miR-122. The data demonstrate that miR-122 plays an important role in HBV-related hepatocarcinogenesis by targeting NDRG3. Thus, miR-122 and NDRG3 represent key diagnostic markers and potential therapeutic targets for HBV-related HCC.

miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma.

Recent studies have revealed that microRNA-29c (miR-29c) is involved in a variety of biological processes including carcinogenesis. Here, we report that miR-29c was significantly downregulated in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines as well as in clinical tissues compared with their corresponding controls. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a key regulator in inflammation and immunity, was found to be inversely correlated with miR-29c levels and was identified as a target of miR-29c. Overexpression of miR-29c in HepG2.2.15 cells effectively suppressed TNFAIP3 expression and HBV DNA replication as well as inhibited cell proliferation and induced apoptosis. We conclude that miR-29c may play an important role as a tumor suppressive microRNA in the development and progression of HBV-related HCC by targeting TNFAIP3. Thus miR-29c and TNFAIP3 represent key diagnostic markers and potential therapeutic targets for the prevention and treatment of HBV infection.