Acteoside and isoacteoside alleviate renal dysfunction and inflammation in lipopolysaccharide-induced acute kidney injuries through inhibition of NF-κB signaling pathway.

Acute kidney injury (AKI) is a sudden loss of renal function with a high mortality rate and inflammation is thought to be the underlying cause. The phenylpropanoid components acteoside (ACT) and isoacteoside (ISO), which were isolated from Cistanche deserticola Y.C.Ma, have been reported to have preventive effects against kidney disorders. This study aimed to investigate the anti-inflammatory properties and protective mechanisms of ACT and ISO. In this investigation, kidney function was assessed using a semi-automatic biochemical analyzer, histopathology was examined using Hematoxylin-Eosin staining and immunohistochemistry, and the concentration of inflammatory cytokines was assessed using an enzyme-linked immunosorbent assay (ELISA) test. In addition, using Western blot and q-PCR, the expression of proteins and genes connected to the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced AKI was found. The findings showed that under AKI intervention in LPS group, ACT group and ISO group, the expression of Rela (Rela gene is responsible for the expression of NFκB p65 protein) and Tlr4 mRNA was considerably elevated (P<0.01), which led to a significant improvement in the expression of MyD88, TLR4, Iκ-Bɑ and NF-κB p65 protein (P<0.001). The levels of Alb, Crea and BUN (P<0.001) increased along with the release of downstream inflammatory factors such as IL-1ß, IL-6, Cys-C, SOD1 and TNF-α (P<0.001). More importantly, the study showed that ISO had a more favorable impact on LPS-induced AKI mice than ACT. In conclusion, by inhibiting NF-κB signaling pathway, ACT and ISO could relieve renal failure and inflammation in AKI, offering a fresh possibility for the therapeutic management of the condition.

[Characterization of Metal Elements in Atmospheric PM2.5 and Health Risk Assessment in Heze in Winter from 2017 to 2018].

Atmospheric PM2.5 samples were collected in Heze, Shandong Province, from a total of three sampling sites at Heze College, Huarun Pharmacy, and a wastewater treatment plant between October 15, 2017 and January 31, 2018, to determine the concentrations of 21 metal elements in PM2.5 using inductively coupled plasma mass spectrometry (ICP-MS). The degree of elemental enrichment was also discussed, the health risks and potential heavy metal ecological risks were assessed. The results showed that ρ (PM2.5) ranged from 26.7 to 284.1 µg·m-3 at the three sampling sites during the sampling period, and the concentration values did not differ significantly, all of which were at high pollution levels. The highest concentrations of K were found in the three sampling sites, accounting for 31.03%, 39.47%, and 38.43% of the total, respectively, mainly due to the high contribution of biomass burning in autumn and winter in Heze, a large agricultural city. The highest concentrations of Zn, 89.70, 84.21, and 67.68 ng·m-3, were found in the trace elements at the three sampling sites, respectively. The enrichment factor results showed that the enrichment factor values of Zn, Pb, Sn, Sb, Cd, and Se were higher than 100, among which the enrichment factors of Cd and Se were higher than 2 000 and 4 000, respectively, which were significantly influenced by anthropogenic activities and might have been related to industrial production, metal smelting, road sources, and coal combustion emissions. The health risk results showed that there was some potential non-carcinogenic risk (HQ>0.1 for children and adults) for As and a combined potential non-carcinogenic risk (HI>0.1) and some potential carcinogenic risk (CRT>1×10-6) for both children and adults at the three sampling sites. There was a more significant carcinogenic risk (CRT>1×10-4) for adults at the wastewater treatment plant, and the slightly higher carcinogenic risk for adults than that for children may have been related to the longer outdoor activity and higher PM2.5 exposure for adults. The elements with the highest potential ecological risk values were Cd, As, and Pb, with Cd exhibiting a very high potential ecological risk that should be taken seriously. All three sampling sites showed a very high combined potential ecological risk, with the intensity spatially expressed as Heze College>Huarun Pharmacy>wastewater treatment plant.

Plexiform schwannomas of the sciatic nerve:a case report and review of the literature.

Background: Schwannomas grow slowly, mainly in the head and spine. The extremities schwannomas are rare and easily missed, particularly in patients who also have lumbar disc herniation in addition to sciatic schwannomas. We present a unique case of sciatic schwannoma , which has been considered as a lumbar disease in the past until an MRI of the thigh. Case presentation: A 43-year-old female complained of pain in her low back and left thigh for 10 years. Physical examination showed that her left thigh was swollen and positive Tinel sign. On MRI, we found a series of tumors suspected of schwannomas at the back of her left thigh. After obtaining the patient's consent, we performed intracapsular excision of her tumors. Histological examination of the tumors were consistent with plexiform schwannomas. The patient recovered well after operation and there was no sign of nerve injury or recurrence after follow-up for 11 months. We searched the Pubmed database and found 31 published reports about sciatic schwannomas. Conclusions: Sciatic schwannomas usually occur in middle-aged women, and the main symptom is pain. In addition to palpation, we should pay attention to Tinel sign during physical examination. MRI is very helpful for diagnosis, but histological examination is the only way to make a final diagnosis. Intracapsular resection is the best method for the treatment of schwannomas, although there is still the possibility of recurrence after operation.

Metabolomics and network analysis uncovered profound inflammation-associated alterations in hepatitis B virus-related cirrhosis patients with early hepatocellular carcinoma.

Patients with hepatitis B virus (HBV)-related liver cirrhosis (LC) are at high risk for hepatocellular carcinoma (HCC). Limitations in the early detection of HCC give rise to poor survival in this high-risk population. Here, we performed comprehensive metabolomics on health individuals and HBV-related LC patients with and without early HCC. Compared to non-HCC patients (N = 108) and health controls (N = 80), we found that patients with early HCC (N = 224) exhibited a specific plasma metabolome map dominated by lipid alterations, including lysophosphatidylcholines, lysophosphatidic acids and bile acids. Pathway and function network analyses indicated that these metabolite alterations were closely associated with inflammation responses. Using multivariate regression and machine learning approaches, we identified a five-metabolite combination that showed significant performances in differentiating early-HCC from non-HCC than α-fetoprotein (area under the curve values, 0.981 versus 0.613). At metabolomic levels, this work provides additional insights of metabolic dysfunction related to HCC progressions and demonstrates the plasma metabolites might be measured to identify early HCC in patients with HBV-related LC.

Wrist-ankle acupuncture for the treatment of acute orthopedic pain after surgery: a meta-analysis.

BACKGROUND: Wrist-ankle acupuncture (WAA) has been reported in the treatment of acute pain in orthopedic surgery. However, the effects of WAA on acute pain were controversial in the current studies. Therefore, the purpose of this meta-analysis was to critically evaluate the effects of WAA on acute pain in orthopedic surgery. METHODS: Several digital databases were searched from the inception of databases to July 2021, including CNKI, VIP, Wanfang, CBM, Pubmed, Cochrane Central Register of Controlled Trials, Embase, Medline, and Web of Science Core Collection. The risk of bias was evaluated using the Cochrane collaboration criteria. The primary outcome indicators included pain score, pain killer dosage, analgesia satisfaction, and adverse reaction incidence. All analyses were performed with Review Manager 5.4.1. RESULT: A total of 10 studies with 725 patients with orthopedic surgery (intervention group: 361, control group: 364) were included in this meta-analysis. The results demonstrated that the pain score of the intervention group was lower than the control group, and the difference was statistically significant [MD = - 0.29, 95%CI (- 0.37, - 0.21), P < 0.0001]. Compared with the control group, the patient in the intervention group used smaller amounts of pain killer [MD = - 0.16, 95%CI (- 0.30, - 0.02), P = 0.02]. The satisfaction of patients on pain relief was also higher in the intervention group, and the difference was statistically [OR = 0.25, 95%CI (0.15,0.41), P < 0.0001]. CONCLUSION: WAA has a certain effect on acute pain in orthopedic surgery, and the effect of WAA combined with other therapies is better than that of not using WAA therapy.

Nomogram to predict malignancy in branch duct type intraductal papillary mucinous neoplasms.

Prediction of malignancy in branch duct (BD)-type intraductal papillary mucinous neoplasms (BD-IPMNs) is difficult. In this retrospective study, we showed the performance of imaging biomarker and biochemical biomarker in identifying the malignant BD-IPMNs. A total of 97 patients with pathological proved BD-IPMNs were included in this study. Imaging data were collected from magnetic resonance imaging (MRI). Malignant BD-IPMNs were defined as those with high grade dysplasia and invasive carcinoma. There were 10 patients with malignant BD-IPMNs (10.3%). Significant difference was found in prevalence of mural nodule and tumor size >3.0 cm between patients with and without malignant BD-IPMNs (44.4% vs 3.1%, P < .01; 80.0% vs 33.3%, P < .01). Significant differences were observed in mural nodule and elevated carbohydrate antigen 19-9 (CA19-9) between patients with and without invasive carcinoma (40.0% vs 7.6, P = .05; 60% vs 15.3%, P = .04). Mural nodule and tumor size >3.0 cm were the independent associated factor for malignant BD-IPMNs. The odds ratio (OR) was 5.22 (95% confidence interval [CI]: 1.04-31.16) for mural nodule and was 6.80 (95% CI: 1.16-39.71) for cyst size >3.0 cm. The combined model of mural nodule and tumor size showed good performance in identifying malignant BD-IPMNs (area under the curve [AUC] = 0.82, 95%CI: 0.67-0.97). Our data show that mural nodule and cystic size can be used as predictor of malignancy in BD-IPMN. The predictive performance is acceptable.

3D Automatic Segmentation of Brain Tumor Based on Deep Neural Network and Multimodal MRI Images.

Brain tumor segmentation is an important content in medical image processing, and it is also a very common research in medicine. Due to the development of modern technology, it is very valuable to use deep learning (DL) and multimodal MRI images to study brain tumor segmentation. In order to solve the problems of low efficiency and low accuracy of brain tumor segmentation, this paper proposes DL to conduct research on multimodal MRI image segmentation, aiming to make accurate diagnosis and treatment for doctors. In addition, this paper constructs an automatic diagnosis system for brain tumors, uses GLCM and discrete wavelet transform (DWT) to extract features from MRI images, and then uses a convolutional neural network (CNN) for final diagnosis; finally, through four. The comparison of the results between the two algorithms proves that the CNN algorithm has the better processing power and higher efficiency.

Engineered Polymer-Supported Biorthogonal Nanocatalysts Using Flash Nanoprecipitation.

Transition-metal catalysts (TMCs) effect bioorthogonal transformations that enable the generation of therapeutic agents in situ, minimizing off-target effects. The encapsulation of insoluble TMCs into polymeric nanoparticles to generate "polyzymes" has vastly expanded their applicability in biological environments by enhancing catalyst solubility and stability. However, commonly used precipitation approaches provide limited encapsulation efficiency in polyzyme fabrication and result in a low catalytic activity. Herein, we report the creation of polyzymes with increased catalyst loading and optimized turnover efficiency using flash nanoprecipitation (FNP). Polyzymes with controlled size and catalyst loading were fabricated by tuning the process conditions of FNP. The biological applicability of polyzymes was demonstrated by efficiently transforming a non-toxic prodrug into the active drug within cancer cells.

Computed Tomography Image Features under Deep Learning Algorithm Applied in Staging Diagnosis of Bladder Cancer and Detection on Ceramide Glycosylation.

The research is aimed at investigating computed tomography (CT) image based on deep learning algorithm and the application value of ceramide glycosylation in diagnosing bladder cancer. The images of ordinary CT detection were improved. In this study, 60 bladder cancer patients were selected and performed with ordinary CT detection, and the detection results were processed by CT based on deep learning algorithms and compared with pathological diagnosis. In addition, Western Blot technology was used to detect the expression of glucose ceramide synthase (GCS) in the cell membrane of tumor tissues and normal tissues of bladder. The comparison results found that, in simple CT clinical staging, the coincidence rates of T1 stage, T2a stage, T2b stage, T3 stage, and T4 stage were 28.56%, 62.51%, 78.94%, 84.61%, and 74.99%, respectively; and the total coincidence rate of CT clinical staging was 63.32%, which was greatly different from the clinical staging of pathological diagnosis (P < 0.05). In the clinical staging of algorithm-based CT test results, the coincidence rates of T1 stage and T2a stage were 50.01% and 91.65%, respectively; and those of T2b stage, T3 stage, and T4 stage were 100.00%; and the total coincidence rate was 96.69%, which was not obviously different from the clinical staging of pathological diagnosis (P > 0.05). Therefore, it could be concluded that the algorithm-based CT detection results were more accurate, and the use of CT scans based on deep learning algorithms in the preoperative staging and clinical treatment of bladder cancer showed reliable guiding significance and clinical value. In addition, it was found that the expression level of GCS in normal bladder tissues was much lower than that in bladder cancer tissues. This indicated that the changes in GCS were closely related to the development and prognosis of bladder cancer. Therefore, it was believed that GCS may be an effective target for the treatment of bladder cancer in the future, and further research was needed for specific conditions.

The Influence of Diabetes Mellitus on Rotator Cuff Repair: A Systematic Review and Meta-Analysis.

BACKGROUND: Clinical outcomes after rotator cuff repair associated with diabetes mellitus (DM) are generally favorable, but no study has attempted to establish the influence of DM on outcomes after rotator cuff repair. PURPOSE: To conduct a meta-analysis of clinical studies evaluating patient outcomes between people with DM and people without DM after rotator cuff repair. STUDY DESIGN: Meta-analysis. METHODS: A literature search of the Embase, PubMed, and Cochrane Library databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Cohort studies and case-control studies about clinical outcomes after rotator cuff repair comparing people with DM and people without DM were included. Statistical analysis was performed with RevMan (v 5.3.3). RESULTS: Nine clinical studies that met the inclusion criteria were identified and included a total of 314 patients treated with DM and 1092 patients without DM. The failure rate was significantly higher in the DM group than in Non-DM group (23.97% compared with 16.60%, OR: 2.39; 95% CI, 1.69-3.37; p < 0.001). The postoperative retear rate and showed a significant difference between the two groups (24.5% and 13.7%; OR: 2.41; 95% CI, 1.57-3.71; p<0.001). The DM group showed a higher rate of postoperative unhealed cuff than the Non-DM group(41.81% and 25.23%; OR: 2.14; 95% CI, 1.69-3.37; p=0.01).Postoperative Range of motion(ROM) at 12 months after surgery show a significant difference in the range of external rotation between two groups (WMD: -6.02; 95% CI, -7.54 to -4.50; p<0.001). The preoperative Japanese Orthopaedic Association (JOA) score, the comparison of pre- and post-operative JOA scores showed a significant difference in the DM and Non-DM group(p<0.001). The postoperative JOA score, the pre- and post-operative muscle strength, the pre- and post-operative visual analog scale (VAS) show significant difference between the DM and Non-DM group(p<0.001). The postoperative infection rates, the rates of postoperative shoulder stiffness, the preoperative ROM, the postoperative ROM at 6 months, the postoperative ROM at 12 months of forward flexion and abduction, the American Shoulder and Elbow Surgeons score, the University of California, Los Angeles scores, and the preoperative Constant-Murley scores show no significant difference between the two groups. CONCLUSION: This meta-analysis indicates that DM may be relative to a higher rate of shoulder retear and cuff unhealing. However, patients with DM can achieve great clinical outcomes after cuff repair, compared to patients without DM.

The Osteogenic Effect of Local Delivery of Vancomycin and Tobramycin on Bone Marrow Stromal Cells.

PURPOSE: Bone tissue infections are a difficult problem in orthopedic surgery. Topical application of vancomycin and tobramycin powder has been proved to significantly reduce infection rates. However, the osteogenic effect of the topical application of these two antibiotics is unclear. In this study, the osteogenic effect of local delivery antibiotics on bone regeneration was investigated in vitro. METHODS: Bone marrow stromal cells (BMSCs) were incubated in the presence of vancomycin (14.28µg/mL), tobramycin (28.57µg/mL), or vancomycin combined with tobramycin (vancomycin 14.28µg/mL and tobramycin 28.57µg/mL). Cell viability, proliferation, and migration were analyzed. The alizarin red staining as well as the alkaline phosphatase staining was investigated. Then, the quantitative real-time (qRT)-PCR of osteogenic mRNA expression levels were also evaluated. RESULTS: The results showed that vancomycin combined with tobramycin has no adverse effect on the viability and proliferation of BMSCs. The topical application of vancomycin alone may interfere with the bone regenerative processes. However, the tobramycin can promote the osteogenic differentiation of BMSCs and also rescue the osteogenic potential of BMSCs inhibited by vancomycin both in vitro. CONCLUSION: From this in vitro study, local application of vancomycin combined with tobramycin does not affect the osteogenic potential of BMSCs.

Three-Dimensional Printed Titanium Scaffolds Enhance Osteogenic Differentiation and New Bone Formation by Cultured Adipose Tissue-Derived Stem Cells Through the IGF-1R/AKT/Mammalian Target of Rapamycin Complex 1 (mTORC1) Pathway.

BACKGROUND This study aimed to investigate the effects of three-dimensional (3D) printed titanium (3DTi) scaffolds on osteogenic differentiation and new bone formation by 3D cultured adipose tissue-derived stem cells (ADSCs) in vitro, and the effects of bone regeneration in vivo using a full-thickness mandibular defect rat model, and the mechanisms involved. MATERIAL AND METHODS Alpha-beta titanium alloy (Ti6Al4V) 3DTi scaffolds were prepared with Cellmatrix hydrogel and 3D culture medium. ADSCs were impregnated into the 3DTi scaffolds. ADSC viability and proliferation were assessed using the cell counting kit-8 (CCK-8) assay, and alkaline phosphatase (ALP) levels were measured. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to assess the expression of osteogenesis-related mRNA for RUNX2, OPN, OCN, and IGF-1 genes and proteins. A rat model of full-thickness mandibular defect was evaluated with micro-computed tomography (microCT) scanning, and histochemistry with Alizarin red and von Giesen's stain were used to evaluate osteogenesis. RESULTS ADSC viability and proliferation were not affected by culture with 3DTi scaffolds. Expression of osteogenesis-related mRNA and proteins for RUNX2, OPN, OCN, and IGF-1, expression of ALP, and histochemical findings showed that the use of 3DTi scaffolds enhanced osteogenic differentiation and new bone formation by ADSCs, with upregulation of components of the IGF-1R/AKT/mTORC1 pathway. CONCLUSIONS The 3D culture of ADSCs with 3DTi scaffolds enhanced osteogenic differentiation and new bone formation through the IGF-1R/AKT/mTORC1 pathway. This improved method of osteointegration may have clinical application in the preparation of bone grafts before implantation for improved repair of mandibular bone defects.

Decrease of MiR-31 induced by TNF-α inhibitor activates SATB2/RUNX2 pathway and promotes osteogenic differentiation in ethanol-induced osteonecrosis.

PURPOSE: Suppressed osteogenic differentiation is considered a main cause of ethanol-induced osteonecrosis. Tumor necrosis factor α (TNF-α) and miR-31 have been reported to be involved in the osteogenic induction. This study aimed to explore a possible molecular mechanism regulating osteogenic differentiation in ethanol-induced osteonecrosis bone marrow stromal stem cells (BMSCs). METHODS: Alizarin red staining was used to examine the level of mineralization in osteogenic differentiation process. Alkaline phosphatase assay was applied to the validation of ALP level which was essential to bone mineralization. The level of osteogenesis markers was determined by western blot assay, whereas the fluctuations of messenger RNA levels were tested by quantitative real-time polymerase chain reaction. Microarray analysis was conducted to identify differentially expressed genes, because the possible target relationship was predicted and validated by miRBase and luciferase reporter assay, respectively. Colony forming unit of fibroblast assay was used to observe the proliferation of BMSCs. RESULTS: BMSCs from patients with ethanol-induced osteonecrosis exhibited weaker osteogenic differentiation and proliferation abilities. TNF-α inhibitor added in the osteogenic medium significantly enhanced the osteogenic differentiation ability and BMSCs proliferation ability. TNF-α by regulating miR-31 downregulated the expressions of RUNX2 and SATB2, two contributors of osteoblast differentiation, further suppressed osteogenic differentiation. On the contrary, TNF-α inhibitor could promote osteogenic differentiation in BMSCs from patients with ethanol-induced osteonecrosis. CONCLUSION: TNF-α inhibitor could downregulate miR-31 expressions, which directly promoted SATB2 and RUNX2 expressions and enhanced osteogenic differentiation of BMSCs from patients with ethanol-induced osteonecrosis.

Morphology Tuning of Aggregation-Induced Emission Probes by Flash Nanoprecipitation: Shape and Size Effects on in Vivo Imaging.

Aggregation-induced emission (AIE) imaging probes have recently received considerable attention because of their unique property of high performance in the aggregated state and their imaging capability. However, the tendency of AIE molecules to aggregate into micron long irregular shapes, which significantly limits their application in vivo, is becoming a serious issue that needs to be addressed. Here, we introduce a novel engineering strategy to tune the morphology and size of AIE nanoaggregates, based on flash nanoprecipitation (FNP). Quinolinemalononitrile (ED) is encapsulated inside properly selected amphiphilic block copolymers of varying concentration. This leads to a variety of ED particle morphologies with different sizes. The shape and size are found to have strong influences on tumor targeting both in vitro and in vivo. The current results therefore indicate that the FNP method together with optimal choice of an amphiphilic copolymer is a universal method to systematically control the aggregation state of AIE materials and hence tune the morphology and size of AIE nanoaggregates, which is potentially useful for precise imaging at specific tumor sites.

Fabrication of Charge-Conversion Nanoparticles for Cancer Imaging by Flash Nanoprecipitation.

Traditional charge-conversion nanoparticles (NPs) need the breakage of acid-labile groups on the surface, which impedes the rapid response to the acidic microenvironment. Here, we developed novel rodlike charge-conversion NPs with amphiphilic dextran- b-poly(lactic- co-glycolic acid), poly(2-(dimethylamino) ethylmethylacrylate)- b-poly(ε-caprolactone), and an aggregation-induced emission-active probe through flash nanoprecipitation (FNP). These NPs exhibit reversible negative-to-positive charge transition at a slightly acidic pH relying on the rapid protonation/deprotonation of polymers. The size and the critical charge-conversion pH can be further tuned by varying the flow rate and polymer ratio. Consequently, the charge conversion endows NPs with resistance to protein adsorption at physiological pH and enhanced internalization to cancer cells under acidic conditions. Ex vivo imaging on harvest organs shows that charge-conversion NPs were predominantly distributed in tumors after intravenous administration to mice due to the robust response of NPs to the acidic microenvironment in tumor tissue, whereas control NPs or free probes were broadly accumulated in tumor, liver, kidney, and lung. These results suggest the great potential of the current FNP strategy in the facile and generic fabrication of charge-conversion NPs for tumor-targeting delivery of drugs or fluorescent probes.

Stabilization of Notch1 by the Hsp90 Chaperone Is Crucial for T-Cell Leukemogenesis.

Purpose: Notch1 deregulation is assuming a focal role in T-cell acute lymphoblastic leukemia (T-ALL). Despite tremendous advances in our understanding of Notch1 transcriptional programs, the mechanisms by which Notch1 stability and turnover are regulated remain obscure. The goal of the current study is to identify intracellular Notch1 (ICN1, the activated form of Notch1) binding partner(s) regulating its stability and activity. Experimental Design: We employed immunoaffinity purification to identify ICN1-associating partner(s) and used coimmunoprecipitation to verify the endogenous protein interaction. Pharmacologic or short hairpin RNA-mediated inhibition was applied in loss-of-function assays to assess the role of tentative binding partner(s) in modulating ICN1 protein stability as well as affecting T-ALL cell expansion in vitro and in vivo Mechanistic analysis involved protein degradation and polyubiquitination assays. Results: We identify the Hsp90 chaperone as a direct ICN1-binding partner essential for its stabilization and transcriptional activity. T-ALL cells exhibit constitutive endogenous ICN1-Hsp90 interaction and Hsp90 depletion markedly decreases ICN1 levels. The Hsp90-associated E3 ubiquitin ligase Stub1 mediates the ensuring proteasome-dependent ICN1 degradation. Administration of 17-AAG or PU-H71, two distinct Hsp90 inhibitors, depletes ICN1, inhibits T-ALL cell proliferation, and triggers dramatic apoptotic cell death. Systemic treatment with PU-H71 reduces ICN1 expression and profoundly inhibits murine T-ALL allografts as well as human T-ALL xenografts. Conclusions: Our findings demonstrate Hsp90 blockade leads to ICN1 destabilization, providing an alternative strategy to antagonize oncogenic Notch1 signaling with Hsp90-selective inhibitors. Clin Cancer Res; 23(14); 3834-46. ©2017 AACR.

Real-Time Tracking and In Vivo Visualization of ß-Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe.

Development of "smart" noninvasive bioimaging probes for trapping specific enzyme activities is highly desirable for cancer therapy in vivo. Given that ß-galactosidase (ß-gal) is an important biomarker for cell senescence and primary ovarian cancers, we design an enzyme-activatable ratiometric near-infrared (NIR) probe (DCM-ßgal) for the real-time fluorescent quantification and trapping of ß-gal activity in vivo and in situ. DCM-ßgal manifests significantly ratiometric and turn-on NIR fluorescent signals simultaneously in response to ß-gal concentration, which makes it favorable for monitoring dynamic ß-gal activity in vivo with self-calibration in fluorescent mode. We exemplify DCM-ßgal for the ratiometric tracking of endogenously overexpressed ß-gal distribution in living 293T cells via the lacZ gene transfection method and OVCAR-3 cells, and further realize real-time in vivo bioimaging of ß-gal activity in colorectal tumor-bearing nude mice. Advantages of our system include light-up ratiometric NIR fluorescence with large Stokes shift, high photostability, and pH independency under the physiological range, allowing for the in vivo real-time evaluation of ß-gal activity at the tumor site with high-resolution three-dimensional bioimaging for the first time. Our work provides a potential tool for in vivo real-time tracking enzyme activity in preclinical applications.

Antibacterial activity of graphene supported FeAg bimetallic nanocomposites.

We report the simple one pot synthesis of iron-silver (FeAg) bimetallic nanoparticles with different compositions on graphene support. The nanoparticles are well dispersed on the graphene sheet as revealed by the TEM, XRD, and Raman spectra. The antibacterial activity of graphene-FeAg nanocomposite (NC) towards Bacillus subtilis, Escherichia coli, and Staphylococcus aureus was investigated by colony counting method. Graphene-FeAg NC demonstrates excellent antibacterial activity as compared to FeAg bimetallic without graphene. To understand the antibacterial mechanism of the NC, oxidative stress caused by reactive oxygen species (ROS) and the glutathione (GSH) oxidation were investigated in the system. It has been observed that ROS production and GSH oxidation are concentration dependent while the increase in silver content up to 50% generally enhances the ROS production while ROS decreases on further increase in silver content. Graphene loaded FeAg NC demonstrates higher GSH oxidation capacity than bare FeAg bimetallic nanocomposite. The mechanism study suggests that the antibacterial activity is probably due to membrane and oxidative stress produced by the nanocomposites. The possible antibacterial pathway mainly includes the non-ROS oxidative stress (GSH oxidation) while ROS play minor role.

Analysis of differences in the molecular mechanism of rheumatoid arthritis and osteoarthritis based on integration of gene expression profiles.

BACKGROUND: We aimed to elucidate the molecular mechanisms underlying rheumatoid arthritis (RA) and osteoarthritis (OA) and analyze the mechanism differences between them. METHODS: The gene expression profile of GSE1919, GSE12021, GSE21959 and GSE48780 were downloaded from Gene Expression Omnibus. Total 165 samples of synovial fibroblasts (118 RA samples, 15 OA samples and 32 normal controls) were used. The differentially expressed genes (DEGs) in RA samples but no differences in OA samples (RA.DEGs) and genes in OA samples but no differences in RA samples (OA.DEGs) were screened using limma package. Functional enrichment analysis was performed using DAVID. Moreover, transcriptional regulatory network (TRN) and microRNA regulatory network were constructed. RESULTS: Total 211 RA.DEGs (96 up- and 115 down-regulate) and 497 OA.DEGs (224 up- and 273 down-regulated) were identified. TRN analysis showed that C-ETS-1 and P53 were important transcription factors. C-ETS-1 could interact with matrix metallopeptidase 1 (MMP1) and CD53 while P53 could interact with epidermal growth factor receptor (EGFR) and dual specificity phosphatase 1 (DUSP1). Besides, v-myc avian myelocytomatosis viral oncogene homolog (MYC) and interleukin 1, beta (IL1B) could be regulated by the most microRNAs in microRNA regulatory network. Our study indicates that ETS-1 may contribute to RA progression by up-regulation of MMP1 and result in OA progression via up-regulating CD53. CONCLUSIONS: P53 may be involved in the progression of RA and OA via targeting downstream EGFR and DUSP1 respectively. Besides, MYC and IL1B may play an important role in OA progression via the regulation of microRNAs.

Efficient degradation of trichloroethylene in water using persulfate activated by reduced graphene oxide-iron nanocomposite.

Graphene oxide (GO) and nano-sized zero-valent iron-reduced graphene oxide (nZVI-rGO) composite were prepared. The GO and nZVI-rGO composite were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), energy-dispersive spectroscopy (EDS), and Raman spectroscopy. The size of nZVI was about 6 nm as observed by TEM. The system of nZVI-rGO and persulfate (PS) was used for the degradation of trichloroethylene (TCE) in water, and showed 26.5% more efficiency as compared to nZVI/PS system. The different parameters were studied to determine the efficiency of nZVI-rGO to activate the PS system for the TCE degradation. By increasing the PS amount, TCE removal was also improved while no obvious effect was observed by varying the catalyst loading. Degradation was decreased as the TCE initial concentration was increased from 20 to 100 mg/L. Moreover, when initial solution pH was increased, efficiency deteriorated to 80%. Bicarbonate showed more negative effect on TCE removal among the solution matrix. To better understand the effects of radical species in the system, the scavenger tests were performed. The •SO4(-) and •O2(-) were predominant species responsible for TCE removal. The nZVI-rGO-activated PS process shows potential applications in remediation of highly toxic organic contaminants such as TCE present in the groundwater. Graphical abstract Persulfate activated by reduced graphene oxide and nano-sized zero-valent iron composite can be used for efficient degradation of trichloroethylene (TCE) in water.