Imatinib-induced ulcerative colitis.

INTRODUCTION: Imatinib, a tyrosine kinase inhibitor, is the first-line therapy for patients with KIT mutation in gastrointestinal stromal tumor (GIST). Nausea, vomiting, diarrhea, dyspepsia and abdominal pain are common gastrointestinal adverse reactions of imatinib, but imatinib-induced ulcerative colitis (UC) is rarely reported. CASE REPORT: We presented a case of UC induced by imatinib in a 56-year-old male patient who experienced this adverse event after 5 years of imatinib 400 mg/d treatment following GIST resection. MANAGEMENT AND OUTCOME: The patient's diarrhea and bloody stools showed significant improvement following the discontinuation of imatinib therapy and administration of antidiarrheal medications. Then, imatinib was restarted at a daily dosage of 400 mg. DISCUSSION: UC is a rare adverse event associated with imatinib. Physicians should consider the possibility of UC induced by imatinib when patients present with diarrhea and bloody stool after receiving imatinib treatment. This case offered objective evidence of UC induced by imatinib.

Clusterbody Enables Flow Sorting-Assisted Single-Cell Mass Spectrometry Analysis for Identifying Reversal Agent of Chemoresistance.

Identifying effective reversal agents overcoming multidrug resistance with causal mechanisms from an efflux pump protein is of vital importance for enhanced tumor chemotherapy in clinic. To achieve this end, we construct a metal cluster-based probe, named clusterbody, to develop flow sorting-assisted single-cell mass spectrometry analysis. This clusterbody synthesized by biomimetic mineralization possesses an antibody-like property to selectively recognize an efflux pump protein. The intrinsic red fluorescence emission of the clusterbody facilitates fluorescence-activated high-throughput cell sorting of subpopulations with different multidrug resistance levels. Furthermore, based on the accurate formula of the clusterbody, the corresponding protein abundance at the single-cell level is determined through detecting gold content via precise signal amplification by laser ablation inductively coupled plasma mass spectrometry. Therefore, the effect of reversal agent treatment overcoming multidrug resistance is evaluated in a quantitative manner. This work opens a new avenue to identify reversal agents, shedding light on developing combined or synergetic tumor therapy.

An uncommon case of gastrointestinal bleeding: Meckel's diverticulum with ectopic gastric mucosa.

A 25-year-old woman visited our department due to intermittent defecation of black stool and periumbilical pain for 2 years. Abdominal physical examination showed no obvious abnormality. Laboratory examination showed positive fecal occult blood. Because bleeding lesions were not found by gastroscopy or colonoscopy, she underwent double-balloon enteroscopy examination. It was found that a diverticulum was formed in the terminal ileum, with blood exudation. After repeated washing, the blood disappeared. However, after a period of time, blood exudation could still be detected there. She was diagnosed as Meckel's diverticulum with hemorrhage. Considering the patient's repeated gastrointestinal bleeding, surgical treatment was performed. Surgical specimens showed a 2.5×2.3×1.5 cm3 intestinal diverticulum with a soft texture, and the mucosa was grayish white. Postoperative pathological showed ectopic gastric mucosa with chronic inflammatory cell infiltration. The diverticulum had been found to contain gastric fundus gland tissues which were mainly composed of parietal cells and main cells. The patient recovered well after operation.

Catalytic Clusterbody for Enhanced Quantitative Protein Immunoblot.

To assess low-abundance protein biomarkers associated with tumor progression, we have developed artificial catalytic antibodies based on well-defined metal clusters modified with rationally designed peptides, termed clusterbodies. Such clusterbodies possess favorable integrated features of matched ultrasmall sizes, intrinsic fluorescence, and enzyme-like catalytic and selective recognition properties that are inaccessible to traditional antibodies. Consequently, a quantitative assay with high accuracy and high sensitivity is established by measuring the fluorescence and catalytic chemiluminescence of metal clusters preferentially recognizing the protein biomarker, which is confirmed by the molecular-weight marker references of immunoblotting. The results of quantitative immunoblotting are highly close to that derived from the enzyme-linked immunosorbent assay, implying the reliability of this protocol. Remarkably, the detection limit of the aimed protein achieved is as low as 1.0 pg, one magnitude lower than that of the conventional immunoassay. The significant variation of expression levels of the biomarker in tumor cells evidently indicates their distinguished invasion ability. This platform has potential application in analyzing low-abundance protein biomarkers in complex biological matrixes, which is essential to corroborate tumor malignancy in early stage. It inspires the construction of clusterbody-based precise bioprobes with customized structures and integrative functions for advanced quantitative biosensing.

Is GSH Chelated Pt Molecule Inactive in Anti-Cancer Treatment? A Case Study of Pt6 GS4.

Platinum (Pt) drugs are widely used in anti-cancer treatment although many reports advocated that tumor cells could inactivate Pt drugs via glutathione-Pt (GSH-Pt) adducts formation. To date, GSH chelated Pt molecules have not been assessed in cancer treatment because GSH-Pt adducts are not capable of killing cancer cells, which is widely accepted and well followed. In this report, endogenous biothiol is utilized to precisely synthesize a GSH chelated Pt molecule (Pt6 GS4 ). This Pt6 GS4 molecule can be well taken up by aggressive triple negative breast cancer (TNBC) cells. Subsequently, its metabolites could enter nuclei to interact with DNA, finally the DNA-Pt complex triggers TNBC cell apoptosis via the p53 pathway. Impressively, high efficacy for anti-cancer treatment is achieved by Pt6 GS4 both in vitro and in vivo when compared with traditional first-line carboplatin in the same dosage. Compared with carboplatin, Pt6 GS4 keeps tumor bearing mice alive for a longer time and is non-toxic for the liver and kidneys. This work opens a route to explore polynuclear Pt compound with accurate architecture for enhancing therapeutic effects and reducing systemic toxicity.

[Silencing miRNA210 Alleviates Myocardial Cell Damage in Myocarditis by Hypoxia Inducible Factor-vascular Endothelial Growth Factor Pathway].

Objective To investigate the effect of miRNA210 on primary myocardial cells in lipopolysaccharide(LPS)-induced myocarditis.Methods CCK8 method was used to detect the effect of miRNA210 on the viability of primary myocardial cells in normal or LPS-induced myocarditis rats.ELISA was performed to detect the secretion of tumor necrosis factor(TNF)-α and interleukin(IL)-1ß after miRNA210 treatment.Flow cytometry was used to detect the apoptosis of primary myocardial cells before and after the intervention.Western blotting was used to detect the expression of TNF-α and IL-1ß.The expression of apoptosis-related proteins bcl-2,bax,caspase-3,and hypoxia inducible factor 1 (HIF1)-vascular endothelial growth factor(VEGF)were detected by Western blotting.Results CCK8 detection results showed that,compared with the control group,the effect of miRNA210 mimic(t=0.000,P=1.000)and siRNA(t=0.686,P=0.500)interference had no significant difference on primary rat cardiomyocytes.The viability of rat primary cardiomyocytes significantly decreased after LPS treatment(t=8.764,P<0.001);compared with LPS group,the viability of rat primary cardiomyocytes significantly increased after inhibition of miRNA210(t=3.576, P=0.012).ELISA showed that,compared with the control group,the expressions of IL-1 ß(t=4.166,P=0.014)and TNF-α(t=6.309,P=0.003)were significantly up-regulated after LPS induction;compared with the LPS group,the expressions of IL-1 ß(t=4.096,P=0.015)and TNF-α(t=4.424,P=0.011)were significantly increased after application of miRNA210 mimic.After silencing miRNA210,IL-1 ß(t=4.287,P=0.012)and TNF-α(t=3.577,P=0.023)were significantly down-regulated.Flow cytometry showed that,compared with the control group,the apoptosis of primary cardiomyocytes induced by LPS was significantly increased(t=32.780,P<0.001);compared with LPS group,the apoptosis induced by LPS was significantly aggravated by miRNA210 mimic(t=7.412,P= 0.002),and the apoptosis rate of primary cardiomyocytes was significantly decreased after miRNA210 was silenced(t=11.720,P<0.001).Western blot analysis showed that,compared with the control group,LPS significantly down-regulated the expression of bcl-2(t=8.346,P=0.001)and increased the expressions of bax(t=12.890,P<0.001)and caspase-3(t=4.331,P=0.012).Compared with LPS group,the expression of bcl-2(t=6.074,P<0.001)was significantly decreased,and the expressions of bax(t=5.376,P=0.022)and caspase-3(t=5.859,P=0.004)were increased after miRNA210 mimic.After silencing miRNA210,the expression of bcl-2 significantly increased(t=3.873,P=0.017),the expressions of bax(t=5.205,P=0.006)and caspase-3(t=2.800,P=0.040)significantly decreased.Compared with the control group,the expressions of HIF1(t =10.380,P=0.001)and VEGF(t=4.973,P=0.008)were significantly up-regulated in LPS group.Compared with LPS group,the expressions of HIF1(t=8.952,P<0.001)and VEGF(t=11.203,P=0.001)were significantly up-regulated after miRNA210 mimic was applied,while HIF1(t=3.893,P=0.017)and VEGF expression(t=3.181,P=0.033)were decreased after miRNA210 was silenced.Compared with LPS group,the expressions of bax(t= 4.899,P=0.008),HIF1(t=2.833,P=0.047),caspase-3(t=2.877,P=0.045),and VEGF(t= 2.994, P=0.040)were significantly decreased,and the expression of bcl-2 was increased(t=3.392,P=0.017).Conclusion Silencing miRNA210 can attenuate LPS-induced cardiomyocyte injury through HIF1-VEGF-mediated apoptotic pathway.

Assembled Vitamin B2 Nanocrystals with Optical Waveguiding and Photosensitizing Properties for Potential Biomedical Application.

Great success has been achieved in recent years in the development of synthetic or assembled nanobiomaterials. Among these, biomolecule-based nanoarchitectures with special optical property are of particular interest. Here, we demonstrate that vitamin B2 nanocrystals assembled as nanorods can be obtained with precise control. Excitingly, such one-dimensional nanostructures not only exhibit intrinsic optical waveguiding properties but also the ability to sensitize oxygen to produce reactive oxygen species. With these properties, we applied the obtained vitamin B2 nanorods under remotely localized light illumination into single tumour cells in vitro for anticancer photodynamic therapy. Further, vitamin B2 nanorods were explored for in vivo photodynamic therapy by using a tumour model. With such bionanostructures, new features and functions of vitamin B2 and its derivatives have been developed.

Label-free Au cluster used for in vivo 2D and 3D computed tomography of murine kidneys.

Kidney disease is a worldwide health hazard. Noninvasive imaging modalities such as computed tomography are often used for diagnosis, to guide treatment, and to assess a disease state over the long-term. The physiology of the kidneys can be assessed with contrast agents. We present an albumin-stabilized Au cluster with red fluorescence and robust X-ray attenuation. In vivo studies revealed distribution of the Au clusters in the liver, spleen, and kidneys, with excretion mostly via the kidneys. Under optimal conditions, this agent can outline the anatomy of mouse kidneys on 2D and 3D computed tomography imaging, with clear visualization of the renal collecting system and ureters. This is a promising agent for kidney visualization and disease diagnosis.

Facile approach to observe and quantify the α(IIb)ß3 integrin on a single-cell.

We report for the first time seeing and counting integrin α(IIb)ß3 on a single-cell level. The proposed method is based on the using of the Au cluster probe. With the fluorescent property of Au24 cluster and the specific targeting ability of peptide, our probe can directly visualize integrin α(IIb)ß3 on the membrane of human erythroleukemia cells (HEL) via confocal microscopy. On the basis of the accurate formula of our probe (Au24Peptide8), the number of integrin α(IIb)ß3 can be precisely counted by quantifying the gold content on a single HEL cell via laser ablation inductively coupled plasma mass spectrometry. Our results reveal that the number of integrin α(IIb)ß3 on a single cell varies from 5.75 × 10(-17) to 9.11 × 10(-17) mol, because of the heteroexpression levels of α(IIb)ß3 on individual cells.

Detection of pH change in cytoplasm of live myocardial ischemia cells via the ssDNA-SWCNTs nanoprobes.

Myocardial ischemia is featured by a significant increase in the cytoplasm proton concentration, and such a proton change may be applied as an index for earlier ischemic heart disease diagnostics. But such a pH change in a live heart cell is difficult to monitor as a normal fluorescent probe cannot specifically transport into the cytoplasm of an ischemic cell. This is because the heart cell contains condensed myofibrils which are tight barriers for a normal probe to penetrate. We design fluorescent probes, single-strand DNA wrapped single-wall carbon nanotubes (ssDNA-SWCNTs), where the ssDNA is labeled by the dye molecule hexachloro-6-carboxyfluorescein (HEX). This nanoprobe could transport well into a live heart cell and locate in the cytoplasm to sensitively detect the intracellular pH change of myocardial ischemia. Briefly, protons neutralize the negative charges of nanoprobes in the cytoplasm. This will weaken the stability of nanoprobes and further tune their aggregation. Such aggregations induce the HEX of some nanoprobes condensed together and further result in their fluorescence quenching. The nanoprobes are advantaged in penetrating condensed myofibrils of the heart cell, and their fluorescence intensity is sensitive to the proton concentration change in the live cell cytoplasm. This new method may provide great assistance in earlier cardiopathy diagnosis in the future.

SIAH1 facilitates the migration and invasion of gastric cancer cells through promoting the ubiquitination and degradation of RECK.

Siah E3 ubiquitin protein ligase 1 (SIAH1) has been reported to participate in the development of several human cancers, including gastric cancer. However, the effect and mechanism of SIAH1 on the migration and invasion of gastric cancer cells need be further explored. Here, we first analyzed the clinical value of SIAH1 in gastric cancer, and found that SIAH1 was up-regulated in gastric cancer and associated with a poor prognosis. In addition, silencing of SIAH1 significantly inhibited the migration and invasion of gastric cancer cells through inhibiting the expression of matrix metalloproteinase-9 (MMP9), while overexpression of SIAH1 had the opposite effect. Molecularly, we provided the evidence that reversion-inducing cysteine-rich protein with Kazal motifs (RECK) was a potential substrate of SIAH1. We determined that SIAH1 could destabilize RECK through promoting its ubiquitination and degradation via proteasome pathway. We also found RECK was involved in SIAH1-regulated gastric cancer cell migration and invasion. In conclusion, SIAH1 is up-regulated in gastric cancer, which promotes the migration and invasion of gastric cancer cells through regulating RECK-MMP9 pathway.

Construction of chrysophanol loaded nanoparticles with N-octyl-O-sulfate chitosan for enhanced nephroprotective effect.

Natural occurring anthraquinone like chrysophanol has been studied because of its anti-diabetic, anti-tumor, anti-inflammatory, hepatoprotective and neuroprotective properties. Nonetheless, its poor water solubility and unstable nature are big concerns in achieving efficient delivery and associated pharmacokinetic and pharmacodynamic effects. Herein, this study sought to solve the above-mentioned problem through development of chrysophanol-loaded nanoparticles to enhance the bioavailability of chrysophanol and to evaluate its anti-renal fibrosis effect in rats. After synthesis of a safe N-octyl-O-sulfate chitosan, we used it to prepare chrysophanol-loaded nanoparticles through dialysis technique before we performed and physical characterization. Also, we tested the stability of the nanoparticles for 21 days at 4 °C and room temperature (25 °C) and evaluated their pharmacokinetics and anti-renal fibrosis effect in rat model of chronic kidney disease (CKD). In terms of results, the nano-preparation demonstrated an acceptable narrow size distribution, wherein the encapsulation rate, size, polydispersed index (PDI) and electrokinetic potential at room temperature were respectively 83.41±0.89 %, 364.88±13.62 nm, 0.192±0.015 and 23.78±1.39 mV. During 21 days of storage, we observed that size of particles and electrokinetic potential altered slightly but the difference was statistically insignificant (p > 0.05). Also, in vitro release studies showed that the formulation reached 84.74 % at 24 h. Chrysophanol nanoparticles showed a 2.57-fold increase in bioavailability compared to unformulated chrysophanol. More importantly, chrysophanol nanoparticles demonstrated certain renal internalization properties and anti-renal fibrosis effects, which could ultimately result in reduced blood-urea nitrogen (BUN), kidney-injury molecule-1 (KIM-1) and serum creatinine (SCr) levels in model rats. In conclusion, the prepared chrysophanol-loaded nanoparticles potentially increased bioavailability and enhanced nephroprotective effects of chrysophanol.

Fluorescent in situ hybridization has limitations in screening NRG1 gene rearrangements.

BACKGROUND: NRG1 fusion is a promising therapeutic target for various tumors but its prevalence is extremely low, and there are no standardized testing algorithms for genetic assessment. MOTHODS: In this study, we analyzed 3008 tumors using Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to screen for NRG1 translocation and p-HER3 expression. RESULTS: Our results demonstrated no cases with p-HER3 positivity through IHC. Nonetheless, 29 cases (0.96%) were identified positive for NRG1 translocation through FISH, with three different signal types. FISH-positive cases were subsequently subjected to next-generation sequencing (NGS) testing. However, only eight of these cases were confirmed with NRG1 fusion through NGS. Notably, we divided FISH into three types and FISH type C group was consistent with NGS results. All NGS NRG1 fusion tumors were adenocarcinomas, with a higher prevalence in females. Our findings indicate that although FISH has limitations in screening NRG1 gene rearrangements, NRG1 fusions can be reliably detected with signals exhibiting low copy numbers of the 5'-end of the gene and no fusion signals. CONCLUSION: Considering the high cost of NGS, FISH remains a useful method for screening NRG1 fusions in various types of tumors. This study provides valuable insights into the molecular mechanisms of NRG1 fusion and identifies potential treatment targets for patients suffering from this disease.

Acute and Subacute Toxicity Evaluation of Erythrocyte Membrane-Coated Boron Nitride Nanoparticles.

Boron nitride nanoparticles have been reported for boron drug delivery. However, its toxicity has not been systematically elucidated. It is necessary to clarify their potential toxicity profile after administration for clinical application. Here, we prepared erythrocyte membrane-coated boron nitride nanoparticles (BN@RBCM). We expect to use them for boron neutron capture therapy (BNCT) in tumors. In this study, we evaluated the acute toxicity and subacute toxicity of BN@RBCM of about 100 nm and determined the half-lethal dose (LD50) of the particles for mice. The results showed that the LD50 of BN@RBCM was 258.94 mg/kg. No remarkable pathological changes by microscopic observation were observed in the treated animals throughout the study period. These results indicate that BN@RBCM has low toxicity and good biocompatibility, which have great potential for biomedical applications.

HER2 overexpression/amplification status in colorectal cancer: a comparison between immunohistochemistry and fluorescence in situ hybridization using five different immunohistochemical scoring criteria.

OBJECTIVE: Although HER2 has gradually become an important therapeutic target for colorectal cancer (CRC), a unified and standard HER2 scoring system was still not established in CRC, and the debatable results of immunohistochemistry and fluorescence in situ hybridization (FISH) in CRC requires further exploration. METHODS: In this study, we use five immunohistochemical (IHC) scoring criteria (i.e., IRS-p, IRS-m, GEA-s, GEA-b and HERACLES) and two FISH criteria to evaluate HER2 status, and further evaluate the correlation between HER2 status and clinicopathological features, survival in a large, unselected Chinese cohort of 664 CRCs. RESULTS: Finally, we set HER2/CEP17 ratio ≥ 2.0, or an average HER2 copy number ≥ 6.0 as FISH-positive threshold and the amplification rate of HER2 gene was 7.08% (47/664).The HER2 positivity (IHC 3+) was 2.71%, 3.16%, 2.56%, 2.71% and 3.16%, according to the IHC scoring criteria of IRS-p, IRS-m, GEA-s, GEA-b and HERACLES, respectively. Set FISH results as the golden standard; receiver-operating characteristic analysis showed that IRS-p had both high sensitivity and specificity than other IHC scoring systems to evaluate HER2 status. Based on IRS-p criterion, There were significant differences in tumor differentiation (p = 0.038), lymphatic vascular invasion (p = 0.001), pN stage (p value = 0.043), and overall survival (p < 0.001) among IHC score 0-3 + groups. Meanwhile, there were significant differences in pT stage (p = 0.031), pN stage (p = 0.009) and overall survival (p < 0.001) among FISH subgroups. CONCLUSION: The IRS-p criterion was more suitable for assessing the HER2 status in CRC patients than other IHC criteria. Whereas for FISH scoring system, only HER2/CEP17 < 2.0, meanwhile HER2cn < 4.0 and HER2cn ≥ 6.0 were subgroups with unique clinicopathological characteristics.

Oxidative Stress Effects of Multiple Pollutants in an Indoor Environment on Human Bronchial Epithelial Cells.

Benzene, toluene, and xylene (denoted as BTX) are normally used in coatings, sealants, curing agents and other home decoration products, which can cause harm to human health. However, traditional studies mostly focus on the toxicity evaluation of a single pollution source, and little attention has been paid to the toxicity reports of multiple pollutants in a complex system. To evaluate the impact of indoor BTX on human health at the cellular level, the oxidative stress effect of BTX on human bronchial epithelial cells was assessed, including cell cytotoxicity, intracellular ROS, cell mitochondrial membrane potential, cell apoptosis, and CYP2E1 expression. The concentrations of BTX introduced into the human bronchial epithelial cell culture medium were determined based on both the tested distribution in 143 newly decorated rooms and the limited concentrations in the indoor air quality (denoted as IAQ) standards. Our study showed that the concentration in line with the standard limit may still pose a serious risk to health. The cellular biology effect studies of BTX showed that BTX, even at concentrations lower than the national standard limit, can still induce observable oxidative stress effects which warrant attention.

Dual peptide nanoparticle platform for enhanced antigen-specific immune tolerance for the treatment of experimental autoimmune encephalomyelitis.

Current therapeutic strategies for autoimmune diseases such as multiple sclerosis (MS) are directed towards nonspecific immunosuppression, which has severe side effects. The induction of antigen-specific tolerance has become an ideal therapy for autoimmune diseases. In this study, we have constructed a dual peptide nanoparticle platform, including the antigen peptide of the primary signal and inhibitory peptide of the co-stimulatory signal, for T-cell activation and to trigger antigen-specific immune tolerance to treat experimental autoimmune encephalomyelitis (EAE), a murine model for MS. The peptide LABL binding with ICAM-1 was encapsulated in PLGA nanoparticles and the antigenic peptide MOG35-55-KKK was then covalently bonded to the surface of the PLGA nanoparticles. In this way, peptide-loaded PLGA nanoparticles (NPsLABL+MOG) were developed. When the dual peptide nanoparticles were administered intravenously either prophylactically or therapeutically to MOG35-55-immunized mice, it completely prevented the occurrence of EAE in the prophylactic therapy trial and decreased inflammatory cell infiltration and the demyelination of the nerve myelin in the spinal cord in both prophylactic and therapeutic trials. In therapeutic experiments especially, the dual peptide nanoparticles a showed stronger inhibitory effect on EAE than the MOG peptide nanoparticles alone. Mechanistically, the dual peptide nanoparticles reduced MHC II and the co-stimulatory molecule CD86 expression of dendritic cells (DCs) on the surface and induced abortive T-cell activation, which eventually led to a decreased infiltration of Th1 and Th17 cells in the central nervous system and showed antigen-specific immune tolerance. The dual peptide nanoparticles have great potential for the treatment of autoimmune diseases by inducing immune tolerance.

A comparison of Remdesivir versus gold cluster in COVID-19 animal model: A better therapeutic outcome of gold cluster.

While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo . We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from gold cluster (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 Mpro. GA directly decreases SARS-CoV-2 viral replication and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 hamsters.

[Changes of brain oxidative stress induced by nano-alumina in ICR mice].

OBJECTIVE: To investigate the brain oxidative stress injury induced by nano-alumina particles in ICR mice. METHODS: Sixty male ICR mice were randomly divided into 6 groups: control group, solvent control group, 100 mg/kg micro-alumina particles group, 3 groups exposed to nano-alumina particles at the doses of 50, 100 and 200 mg/kg. The mice were exposed by nasal drip for 30 days. Then levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in brain tissues of mice were detected. RESULTS: There was no difference of SOD activity in mouse brain between control group [(17.32 +/- 6.23)U/gHb] and 50 mg/kg nano-alumina particles group [(17.89 +/- 1.82) U/gHb]. The SOD activity [(4.93 +/- 2.30)U/gHb] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05). The MDA levels in 3 nano-alumina particles groups were (0.76 +/- 0.13), (1.00 +/- 0.30) and (1.16 +/- 0.39)nmol/ml, respectively, which were significantly higher than that [( 0.24 +/- 0.09)nmol/ml] in control group (P < 0.05). The GSH levels in 3 nano-alumina particles groups were (0.72 +/- 0.08), (0.55 +/- 0.19) and (0.61 +/- 0.20)mg/gpro, respectively, which were significantly lower than that [(1.55 +/- 0.34)mg/gpro]] in control group (P < 0.05). The CAT activity in 50 and 100 mg/kg nano-alumina particles groups were (10.40 +/- 3.84) and (10.40 +/- 2.00)U/mgpro, respectively, which were significantly higher than that [(5.79 +/- 0.96) U/mgpro] in control group (P < 0.05). The CAT activity [(3.25 +/- 1.04)U/mgpro] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05 ). CONCLUSION: Nano-alumina particles can induce the oxidative stress damage in brain tissues of mice.

Metal Cluster-Based Electrochemical Biosensing System for Detecting Epithelial-to-Mesenchymal Transition.

N-cadherin serves as an important oncobiomarker of epithelial-to-mesenchymal transition (EMT) progression, which identifies invasion and metastasis of malignant tumor cells. Although many efforts have been devoted to quantitative detection of N-cadherin, efforts to analyzing the protein of interest at intact cellular levels are scarce. Herein, a metal cluster-based electrochemical biosensing system is developed to determine the expressing levels of N-cadherin during the EMT process of tumor cells. To be specific, a peptide with a unique sequence and function is designed as a reductant and an anchor to synthesize metal clusters in a precise manner. Consequently, peptide-modified metal clusters possess N-cadherin-targeting, photoluminescence, and electrocatalytic properties. Especially, the redox-active metal clusters function as both an electron-transfer mediator and an electronic conductor for enhanced electrochemical sensing. These favorable features enable them as a rapid, sensitive, and reliable whole-cell biosensor, which integrates the fluorescence and electrochemical signals. This cytosensor can accurately quantify the expression levels of N-cadherin on at least 5000 tumor cells. Further, the current signals of model cancer cells gradually increase with EMT progression, indicating tumor cell-type evolution. Our study represents the advanced bioprobe and analytical methods for accurate quantitation of a biomarker to identify tumor progression.