Treatment Of Chemical Agents Research Articles

Mechanisms modulating the activities of intestinal stem cells upon radiation or chemical agent exposure.

Intestinal stem cells (ISCs) are essential for the regeneration of intestinal cells upon radiation or chemical agent damage. As for radiation-induced damage, the expression of AIM2, YAP, TLR3, PUMA or BVES can aggravate ISCs depletion, while the stimulation of TLR5, HGF/MET signaling, Ass1 gene, Slit/Robo signaling facilitate the radio-resistance of ISCs. Upon chemical agent treatment, the activation of TRAIL or p53/PUMA pathway exacerbate injury on ISCs, while the increased levels of IL-22, β-arrestin1 can ease the damage. The transformation between reserve ISCs (rISCs) maintaining quiescent states and active ISCs (aISCs) that are highly proliferative has obtained much attention in recent years, in which ISCs expressing high levels of Hopx, Bmi1, mTert, Krt19 or Lrig1 are resistant to radiation injury, and SOX9, MSI2, clusterin, URI are essential for rISCs maintenance. The differentiated cells like Paneth cells and enteroendocrine cells can also obtain stemness driven by radiation injury mediated by Wnt or Notch signaling. Besides, Mex3a-expressed ISCs can survive and then proliferate into intestinal epithelial cells upon chemical agent damage. In addition, the modulation of symbiotic microbes harboring gastrointestinal (GI) tract is also a promising strategy to protect ISCs against radiation damage. Overall, the strategies targeting mechanisms modulating ISCs activities are conducive to alleviating GI injury of patients receiving chemoradiotherapy or victims of nuclear or chemical accident.

Degradable and Removable Tough Adhesive Hydrogels.

The development of tough adhesive hydrogels has enabled unprecedented adhesion to wet and moving tissue surfaces throughout the body, but they are typically composed of nondegradable components. Here, a family of degradable tough adhesive hydrogels containing ≈90% water by incorporating covalently networked degradable crosslinkers and hydrolyzable ionically crosslinked main-chain polymers is developed. Mechanical toughness, adhesion, and degradation of these new formulations are tested in both accelerated in vitro conditions and up to 16 weeks in vivo. These degradable tough adhesives are engineered with equivalent mechanical and adhesive properties to nondegradable tough adhesives, capable of achieving stretches >20 times their initial length, fracture energies >6kJm-2 ,andadhesionenergies >1000Jm-2 .All degradable systems show complete degradation within 2 weeks under accelerated aging conditions in vitro and weeks to months in vivo depending on the degradable crosslinker selected. Excellent biocompatibility is observed for all groups after 1, 2, 4, 8, and 16 weeks of implantation, with minimal fibrous encapsulation and no signs of organ toxicity. On-demand removal of the adhesive is achieved with treatment of chemical agents which do not cause damage to underlying skin tissue in mice. The broad versatility of this family of adhesives provides the foundation for numerous in vivo indications.

Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer.

Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases.

The extracellular signal-regulated kinases (ERKs) are key transducers of the extracellular signals into intracellular responses and represent major molecular players in tumorigenesis. The aim of this study was to determine how curcumin (CRM) used as an adjuvant supports the apoptotic process induced by a single chemical agent treatment (cisplatin-CisPT) on two head and neck squamous cell carcinoma cell lines (FaDu and PE/CA-PJ49) and the involvement of ERK1/2 and/or p53 activation in this process. Data have shown that the CisPt effect is potentiated by CRM. CRM induced an increase of p53 protein phosphorylation in both cell lines. CisPt decreased p53 protein phosphorylation in FaDu cells, but increased it in PE/CA-PJ49 cells. Data showed that the constitutive expression of activated ERK1/2 protein-kinase was different in the two analyzed tumor cell lines. ERK1/2 activation status was essential for both cell processes, proliferation and apoptosis induced by CisPt and/or CRM treatment on squamous cell carcinoma cells. Our data suggest that p53 phosphorylation in the apoptotic process induced by CRM treatment might require the involvement of ERK1/2. In this regard the CisPt treatment suggested that p53 phosphorylation is ERK1/2 independent in FaDu cells having a p53 gene deletion and ERK1/2 dependent in PE/CA-PJ49 cells having a p53 gene amplification. Moreover, in both tumor cell lines our results support the involvement of p53 phosphorylation-ERK1/2 activation-dependent in the apoptosis induced by combined treatments (CisPt and CRM). The use of CRM as adjuvant could increase the efficiency of chemotherapy by modulating cellular activation processes of ERK1/2 signaling pathways. In conclusion, the particular mode of intervention by which ERK1/2 might influence cell proliferation and/or apoptosis processes depends on the type of therapeutic agent, the cells' particularities, and the activation status of the ERK1/2.

Effects of coupling hybrid processes on the treatment of wastewater containing a commercial mixture of diuron and hexazinone herbicides

This work evaluates the effects of coupling Conductive Diamond Electrochemical Oxidation (CDEO) with electrogenerated peroxide (CDEO-H2O2), iron (II) catalyst (electro-Fenton, EF) and UV irradiation (photoelectron-Fenton, PEF) techniques for the treatment of wastewater containing a commercial mixture of Diuron and Hexazinone herbicides. Although the techniques employed in this study exhibited significant differences in terms of current charge, energy consumption and amounts of byproducts formed, they have shown to be capable of degrading and mineralizing both herbicides (Diuron and Hexazinone). The application of electrooxidation technique with and without hydrogen peroxide generation led to the oxidation of both herbicides, where removal rates ranging from 74% to 99% and 77%–92% were obtained for Hexazinone and Diuron, respectively. Hexazinone and Diuron were completely removed after 90 min in the EF process. PEF was found to be the most efficient technique for having drastically reduced the time for complete degradation of the herbicides, although 25% of organic carbon remained in solution after 120 min of electrolysis. Higher rates of herbicides degradation were obtained in this order: PEF > EF > CDEO/H2O2/UV > CDEO/H2O2 > CDEO > UV. The result indicates that the production of oxidants is promoted by the hybrid processes, and this leads to an improvement in the oxidation of the pollutants. The synergistic coefficient obtained for the coupled techniques were higher than one in terms of both herbicides degradation and Total Organic Carbon (TOC) removal. Two important sub-products of reaction were identified, and their degradation route is in agreement with the reports published in the literature. Essentially, this work draws attention to the synergistic effect caused by the coupling of techniques involving the treatment of chemical agents in wastewater and sheds light on how to use this coupling technique for the development of more efficient treatment processes.

Serine/arginine protein-specific kinase 2 promotes the development and progression of pancreatic cancer by downregulating Numb and p53.

Serine/arginine protein-specific kinase 2 (SRPK2) plays a vital role in the progression of a range of different malignancies, including pancreatic cancer. However, the mechanisms are poorly understood. Previous studies have shown that in hepatocellular carcinoma, SRPK2 knockdown leads to the upregulation of the cell fate determining protein Numb, and in pancreatic cancer cells, Numb knockdown prevents ubiquitin-mediated degradation of p53. In this study, we investigated the relationship between SRPK2, Numb and p53 in the development of pancreatic cancer with or without chemical agent treatment in vitro. SRPK2 expression was upregulated in pancreatic cancer tissues and associated with decreased overall survival in pancreatic cancer patients, indicating that expression of this protein can be used as a marker of unfavourable prognosis. Expression of SRPK2 was positively associated with tumour T stage and Union for International Cancer Control (UICC) stage, and negatively associated with Numb expression in serial tissue sections. In pancreatic cancer cells, SRPK2 downregulation or overexpression led to modulation of Numb and wild-type p53 protein expression in response to oxaliplatin treatment. Furthermore, these three endogenous proteins could be coimmunoprecipitated as a triple complex. Numb or p53 knockdown reversed the upregulation of p53 that was induced by silencing SRPK2. SRPK2 overexpression promoted cell invasion and migration, and decreased chemosensitivity of cancer cells to gemcitabine or oxaliplatin treatment. Conversely, SRPK2 silencing decreased cell invasion and migration and increased chemosensitivity; these effects were reversed by silencing p53 in oxaliplatin-treated pancreatic cancer cells. Our data suggest that SRPK2 negatively regulates p53 by downregulating Numb under chemical agent treatment. Thus, SRPK2 promotes the development and progression of pancreatic cancer in a p53-dependent manner.

Surface modification and physical properties of various UHMWPE‐fiber‐reinforced modified epoxy composites

AbstractTwo surface modification methods—plasma surface treatment and chemical agent treatment—were used to investigate their effects on the surface properties of ultrahigh‐molecular‐weight polyethylene (UHMWPE) fibers. In the analyses, performed using electron spectroscopy for chemical analysis, changes in weight, and scanning electron microscope observations, demonstrated that the two fiber‐surface‐modified composites formed between UHMWPE fiber and epoxy matrix exhibited improved interfacial adhesion and slight improvements in tensile strengths, but notable decreases in elongation, relative to those properties of the composites reinforced with the untreated UHMWPE fibers. In addition, three kinds of epoxy resins—neat DGEBA, polyurethane‐crosslinked DGEBA, and BHHBP‐DGEBA—were used as resin matrices to examine the tensile and elongation properties of their UHMWPE fiber‐reinforced composites. From stress/strain measurements and scanning electron microscope observations, the resin matrix improved the tensile strength apparently, but did not affect the elongation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 655–665, 2007