Qifa Ye

Biocompatible cellulose-based superabsorbent hydrogels with antimicrobial activity

Current superabsorbent hydrogels commercially applied in the disposable diapers have disadvantages such as weak mechanical strength, poor biocompatibility, and lack of antimicrobial activity, which may induce skin allergy of body. To overcome these hassles, we have developed novel cellulose based hydrogels via simple chemical cross-linking of quaternized cellulose (QC) and native cellulose in NaOH/urea aqueous solution. The prepared hydrogel showed superabsorbent property, high mechanical strength, good biocompatibility, and excellent antimicrobial efficacy against Saccharomyces cerevisiae. The presence of QC in the hydrogel networks not only improved their swelling ratio via electrostatic repulsion of quaternary ammonium groups, but also endowed their antimicrobial activity by attraction of sections of anionic microbial membrane into internal pores of poly cationic hydrogel leading to the disruption of microbial membrane. Moreover, the swelling properties, mechanical strength, and antibacterial activity of hydrogels strongly depended on the contents of quaternary ammonium groups in hydrogel networks. The obtained data encouraged the use of these hydrogels for hygienic application such as disposable diapers.

miR‐202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post‐transcriptionally

MicroRNAs have emerged as important regulators of carcinogenesis. In the current study, we observed that microRNA‐202 (miR‐202) is downregulated in hepatocellular carcinoma (HCC) cells and tissues, indicating a significant correlation between miR‐202 expression and HCC progression. Overexpression of miR‐202 in HCC cells suppressed cell proliferation and tumorigenicity, while downregulation of miR‐202 enhanced the cells’ proliferative capacity. Furthermore, we identified low‐density lipoprotein receptor‐related protein 6 (LRP6) as a direct target of miR‐202. miR‐202 suppresses the expression of LRP6 by binding to the 3′‐untranslated region (UTR) of its mRNA. Finally, we found that silencing the expression of LRP6 is the essential biological function of miR‐202 during HCC cell proliferation. Collectively, our findings reveal that miR‐202 is a potential tumor suppressive miRNA that participates in carcinogenesis of human HCC by suppressing LRP6 expression.

Novel fibers fabricated directly from chitin solution and their application as wound dressing

For the first time, pure chitin fibers with relatively high strength, lustrous surface and circular cross section were spun directly from chitin solution dissolved in an NaOH-urea aqueous system with freezing. Subsequently, chitin nonwoven fabrics were constructed from the fresh wet fibers by hot pressing, and tested as wound dressings, showing excellent ability to accelerate healing, owing to the retainment of the intrinsic α-chitin structure.

Construction of cellulose–phosphor hybrid hydrogels and their application for bioimaging

Bioimaging is a key technique for monitoring behavior and activity in vivo and plays an important role in the life science and medical fields. In the present work, for the first time, a new, safe cellulose based hybrid hydrogel was constructed from a cellulose solution containing rare-earth doped phosphor (PP) in an alkali/urea aqueous system using epichlorohydrin as a crosslinker. Its structure and properties were characterized by wide angle X-ray diffraction, FT-IR spectra, solid-state 13C NMR, field emission scanning electron microscopy, UV-vis spectroscopy, fluorescence spectra, and compression tests. The results indicated that the PP particles were tightly embedded in the macroporous cellulose matrix, which not only supplied cavities for PP immobilization through relatively strong intermolecular hydrogen bonding interactions, but also supplied the pore wall as a shell to protect the structure and character of PP. Thus, the cellulose/PP hybrid (CPH) hydrogels emitted relatively strong green fluorescence under a UV lamp, as well as high brightness and long-lasting afterglow. This could avoid harmful radiation in the body and improve signal resolution with lower cell autofluorescence interference. Notably, CPH with strong afterglow could be detected both under the skin and in the stomach with and without excitation light, showing promising prospects as a candidate for bioimaging. Moreover, the hybrid hydrogels exhibited good compressive strength and processability.

The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma

BackgroundIn spite of progress in diagnostics and treatment of Hepatocellular Carcinoma (HCC), its prognosis remains poor, and improved treatment strategies for HCC require detailed understanding of the underlying mechanism. In this investigation we studied the role of Up-frameshift 1 (UPF1) in the tumorigenesis of HCC.MethodsWe determined the expression level of UPF1 in HCC tissues with quantitative real-time PCR and western blotting and then studied its clinical significance. Sodium bisulfite sequencing was used to investigate the regulation of UPF1. We explored the biological significance of UPF1 with gain-and-loss-of-function analyses both in vitro and in vivo. The relationship between UPF1 and SMAD7 was also investigated by western blotting and immunofluorescence.ResultsA great downregulation of UPF1 due to promoter hypermethylation was observed in tumor tissues compared to their adjacent normal tissues. Meanwhile, patients with low UPF1 expression have significantly poorer prognosis than those with high expression. Functionally, UPF1 regulated HCC tumorigenesis both in vitro and in vivo. Moreover, the decreased UPF1 level in HCC reduces NMD efficiency and leads to up-regulation of Smad7, then affects the TGF-β pathway.ConclusionOur findings revealed that UPF1 is a potential tumor suppressive gene and may be a potential therapeutic target for HCC.

miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3

AbstractmicroRNAs play an important role in the progression of hepatocellular carcinoma (HCC). In this study, we found that miR-582-5p expression was downregulated in hepatoma tissues and HCC cell lines. Upregulation of miR-582-5p reduced colony number, inhibited cellular proliferation, and arrested cell cycle in G0/G1 phase. When miR-582-5p was inhibited, the colony number was increased and cellular proliferation and cell cycle were promoted. Further studies showed that miR-582-5p regulated the progression of HCC through directly inhibiting the expression of CDK1 and AKT3, and indirectly inhibiting the expression of cyclinD1.

Increased Expression of Aldehyde Dehydrogenase 2 Reduces Renal Cell Apoptosis During Ischemia/Reperfusion Injury After Hypothermic Machine Perfusion

Hypothermic machine perfusion (MP) can reduce grafts injury after kidney transplantation; however, the mechanism has not been elucidated. In the past decade, many studies showed that aldehyde dehydrogenase 2 (ALDH2) is a protease which can inhibit cell apoptosis. Therefore, this study aims to explore whether ALDH2 takes part in reducing organ damage after MP. Eighteen healthy male New Zealand rabbits (12 weeks old, weight 3.0 ± 0.3 kg) were randomly divided into three groups: normal group, MP group, and cold storage (CS) group (n = 6). The left kidney of rabbits underwent warm ischemia for 35 min through clamping the left renal pedicle and then reperfusion for 1 h. Left kidneys were preserved by MP or CS (4°C for 4 h) in vivo followed by the right nephrectomy and 24-h reperfusion, and then the specimens and blood were collected. Finally, concentration of urine creatinine (Cr), blood urea nitrogen (BUN), and 4-HNE were tested. Renal apoptosis was detected by TUNEL staining, and the expression of ALDH2, cleaved-caspase 3, bcl-2/ bax, MAPK in renal tissue was detected by immunohistochemistry or Western blot; 24 h after surgery, the concentration of Cr in MP group was 355 ± 71μmol/L, in CS group was 511 ± 44 μmol/L (P < 0.05), while the BUN was 15.02 ± 2.34 mmol/L in MP group, 22.64 ± 3.58 mmol/L in CS group (P < 0.05). The rate of apoptosis and expression of cleaved caspase-3, p-P38, p-ERK, and p-JNK in MP group was significantly lower than that in CS group (P < 0.05), while expression of ALDH2 and bcl-2/bax in MP group was significantly higher than that in CS group (P < 0.05); expression of cleaved caspase-3 in both MP and CS group significantly increased as compared with that in normal group (P < 0.05). In conclusion, increased expression of ALDH2 can reduce the renal cell apoptosis through inhibiting MAPK pathway during ischemia/reperfusion injury (IRI) after hypothermic MP.

Gypenoside attenuates hepatic ischemia/reperfusion injury in mice via anti-oxidative and anti-apoptotic bioactivities

Gynostemma pentaphyllum is a traditional Chinese medicine that has previously been used for the treatment of chronic inflammation, hyperlipidemia and liver disease. Gypenoside (GP), the predominant component of Gynostemma pentaphyllum, exhibits a therapeutic effect on chronic hepatic injury, fibrosis and fatty liver disease via its anti-inflammatory and anti-oxidant activity. However, the effect of GP on ischemia/reperfusion (I/R)-induced hepatic injury has, to the best of our knowledge, not previously been investigated. In the present study, a hepatic I/R-injury model was successfully established using C57BL/6 mice. In the treatment group, 50 mg/kg GP was administered orally 1 h prior to ischemia. Following hepatic I/R, the levels of hepatic lipid peroxidation and serum alanine aminotransferase increased, while the ratio of hepatic glutathione (GSH):oxidized GSH was reduced, which was effectively attenuated by pretreatment with GP. Furthermore, an increased protein expression of heme oxygenase-1 in the liver tissues of the I/R mice was attenuated by the administration of GP. In addition, the present study indicated that treatment with GP suppressed the I/R-induced increase in the pro-apoptotic protein levels of Bax and cytochrome c and the activity of caspase-3/8, as well as the I/R-induced decrease in the levels of anti-apoptotic protein Bcl-2. In conclusion, the present study indicated that GP effectively protected against I/R-induced hepatic injury via its anti-oxidative and anti-apoptotic bioactivity.

Construction of blood compatible lysine-immobilized chitin/carbon nanotube microspheres and potential applications for blood purified therapy

Excess bilirubin often evokes hepatobiliary system dysfunction. In the present work, we developed an efficient, safe and blood compatible adsorbent for bilirubin removal from human blood. In view of the highly effective adsorption of carbon nanotubes (CNTs) on bilirubin but with many side effects, and good biocompatibility of chitin but with low efficiency for bilirubin removal, new chitin/carbon nanotube (Ch/CNT) nanofibrous microspheres were constructed from chitin solution in NaOH/urea aqueous system by blending with CNTs. The results of AFM, SEM, and TEM demonstrated that the CNTs were dispersed well in the chitin matrix, and the chitin nanofibers intertwined with CNTs to form hybrid chitin/CNT nanofibers and then weaved into a 3D interconnected network architecture. Moreover, lysine (Lys), a highly specific ligand for bilirubin, was immobilized tightly to the hybrid microspheres to obtain Ch/CNT/Lys. The resultant microspheres possessed large surface area and hierarchical pores including mesopores and micropores, which could allow bilirubin to enter easily and store, leading to highly efficient adsorption. The Ch/CNT/Lys microspheres exhibited excellent bilirubin adsorption property (107.2 mg g-1) and efficient bilirubin clearance rate from real hyperbilirubinemia plasma competing with protein, as well as good cell affinity and blood compatibility, as a result of the combination of the high adsorption of CNTs and inherent biocompatibility of chitin and lysine. Therefore, an effective strategy to develop a novel biocompatible and blood compatible bilirubin adsorbent is provided, showing potential applications for hemoperfusion in blood purified therapy.

The role of lncRNA MALAT1 in the regulation of hepatocyte proliferation during liver regeneration

Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice. We explored the functions of lncRNA MALAT1 with a series of functional analyses in vitro. We found that MALAT1 was upregulated during liver regeneration. Moreover, MALAT1 accelerated hepatocyte proliferation by stimulating cell cycle progression from the G1 to the S phase and inhibiting apoptosis in vitro. In addition, our findings also demonstrated that MALAT1 was regulated by p53 during liver regeneration, and that p53 may be a key upstream regulator of MALAT1 activity. Mechanistically, we found that MALAT1 activated the Wnt/β-catenin pathway by inhibiting the expression of Axin1 and adenomatous polyposis coli (APC), and subsequently promoting the expression of cyclin D1. On the whole, the findings of this study suggest that MALAT1 is a critical molecule for liver regeneration. Pharmacological interventions targeting MALAT1 may thus prove to be therapeutically beneficial in liver failure or liver transplantation by promoting liver regeneration.