Du Huo Ji Sheng Tang inhibits Notch1 signaling and subsequent NLRP3 activation to alleviate cartilage degradation in KOA mice.

BACKGROUND: Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage. METHODS: Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1ß, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR. RESULTS: DHJST reduced tissue swelling and serum and knee cartilage IL-1ß levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1ß in the knee joint of KOA mice were completely limited after Notch1 overexpression. CONCLUSION: DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.

Enhanced refractory organics removal by •OH and 1O2 generated in an electro-oxidation system with cathodic Fenton-like reaction.

Recently, carbon nanotubes coated carbon black and polytetrafluoroethylene (CNTs-C/PTFE) gas diffusion electrode was used as an air-cathode in an electro-oxidation (EO) system for effectively generating hydrogen peroxide (H2O2) through a 2-electron oxygen reduction reaction (ORR). This ORR-EO system not only lowered applied voltage and conserved energy, but the synergistic peroxone (O3/H2O2) reaction could increase hydroxyl radicals (•OH) generation for organics elimination. However, a significant proportion of H2O2 was left in the effluent of ORR-EO, which was a loss of resources and energy. In this study, a Fenton-like reaction for in-situ H2O2 decomposition to generate active oxidation species was inserted by introducing MnO2 into the cathodic catalyst layer, and the sole MnO2/CNTs-C/PTFE air-cathode could accomplish 90% of phenol degradation. When MnO2/CNTs-C/PTFE air-cathode combined with Ti/NATO anode in an ORR-EO system, all anodic oxidation, Fenton-like reaction, and peroxone took place to successfully generate •OH and singlet oxygen (1O2). Over 95% of TOC in phenol and landfill leachate bio-effluent was effectively eliminated, with 20% energy savings compared to the ORR-EO with CNTs-C/PTFE air cathode.

Machine Learning Based on a Multiparametric and Multiregional Radiomics Signature Predicts Radiotherapeutic Response in Patients with Glioblastoma.

METHODS: The MRI images, genetic data, and clinical data of 152 patients with GBM were analyzed. 122 patients from the TCIA dataset (training set: n = 82; validation set: n = 40) and 30 patients from local hospitals were used as an independent test dataset. Radiomics features were extracted from multiple regions of multiparameter MRI. Kaplan-Meier survival analysis was used to verify the ability of the imaging signature to predict the response of GBM patients to radiotherapy before an operation. Multivariate Cox regression including radiomics signature and preoperative clinical risk factors was used to further improve the ability to predict the overall survival (OS) of individual GBM patients, which was presented in the form of a nomogram. RESULTS: The radiomics signature was built by eight selected features. The C-index of the radiomics signature in the TCIA and independent test cohorts was 0.703 (P < 0.001) and 0.757 (P = 0.001), respectively. Multivariate Cox regression analysis confirmed that the radiomics signature (HR: 0.290, P < 0.001), age (HR: 1.023, P = 0.01), and KPS (HR: 0.968, P < 0.001) were independent risk factors for OS in GBM patients before surgery. When the radiomics signature and preoperative clinical risk factors were combined, the radiomics nomogram further improved the performance of OS prediction in individual patients (C-index = 0.764 and 0.758 in the TCIA and test cohorts, respectively). CONCLUSION: This study developed a radiomics signature that can predict the response of individual GBM patients to radiotherapy and may be a new supplement for precise GBM radiotherapy.

Enhanced electro-oxidation/peroxone (in situ) process with a Ti-based nickel-antimony doped tin oxide anode for phenol degradation.

Recently, a novel proof-of-concept oxygen reduction reaction (ORR) based electro-oxidation (EO) process has been developed, which was accomplished by integrating anodic electrochemical oxidation coupled with an in situ electro-peroxone process, by harnessing the anodic by-product O3 reacted with ORR cathode generated H2O2. To further enhance EO coupled in situ electro-peroxone, a nickel and antimony doped tin oxide anodic catalyst layer, namely NATO, was fabricated on Ti mesh to improve anodic oxidation and reinforce the generation of O3, thus promoting in situ Electro-peroxone. As a result, O3 generation rate was enhanced by 12.6%. Complete phenol, as a model organic compound, and 95% of TOC removal were achieved, respectively, during ORR-EO. Through kinetics and instrument analysis, results show that the amount of intermediates accumulated during phenol degradation was much less in this Ti/NATO based ORR-EO system than in a traditional EO system. Moreover, 35.7% of the energy consumption was saved for ORR-EO, owing to its reduced applied voltage and the enhanced in situ electro-peroxone process.

A comparability study of immunohistochemical assays for PD-L1 expression in hepatocellular carcinoma.

Programmed death ligand 1 (PD-L1) protein expression by immunohistochemistry is a promising biomarker for PD-1/PD-L1 blockade in hepatocellular carcinoma. There are a number of commercially available PD-L1 assays. Our study aimed to compare the analytical performance of different PD-L1 assays and evaluate the reliability of pathologists in PD-L1 scoring. Consecutive sections from tumor samples from 55 patients with surgically resected primary hepatocellular carcinoma were stained with four standardized PD-L1 assays (22C3, 28-8, SP142, and SP263). We also correlated the PD-L1 protein level by immunohistochemistry with the mRNA level of those genes associated with tumor immune microenvironment by the NanoString platform. Five pathologists independently assessed PD-L1 expression on tumor cells [tumor proportion score] together with tumor-infiltrating immune cells (combined positive score). The 22C3, 28-8, and SP263 assays had comparable sensitivity in detecting PD-L1 expression, whereas the SP142 assay was the least sensitive assay. The inter-assay agreement measured by intraclass correlation coefficients for the tumor proportion score and combined positive score were 0.646 and 0.780, respectively. The inter-rater agreement was good to excellent (the overall intraclass correlation coefficient for the tumor proportion score and combined positive score was 0.946 and 0.809, respectively). Pathologists were less reliable in scoring combined positive score than tumor proportion score, particularly when using the SP142 assay. Up to 18% of samples were misclassified by individual pathologists in comparison to the consensus score at the cutoff of combined positive score ≥ 1. The combined positive score by the 22C3 assay demonstrated the strongest correlation with immune-related gene mRNA signatures, closely followed by combined positive scores by the 28-8 and SP263 assays. In conclusion, the 22C3, 28-8, and SP263 assays are highly concordant in PD-L1 scoring and suggest the interchangeability of these three assays. Further improvement of the accuracy in assessing PD-L1 expression at a low cutoff is still necessary.

Castleman disease presenting with jaundice: A case report and review of literature.

BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disorder that presents with various symptoms. CD accompanied with jaundice is uncommon since there are only 11 cases reported in the literature. CASE SUMMARY: Here we report a 62-year-old woman who was admitted to the hospital with signs and symptoms of intermittent jaundice. Biochemical tests showed higher serum levels of total and direct bilirubin, and normal serum levels of tumor markers and interleukin-6. Contrast-enhanced computed tomography detected a 6 cm × 4 cm × 2.5 cm mass between the hepatoduodenal ligament and the inferior vena cava. The mass was successfully excised and the patient had a complete resolution of symptoms. A diagnosis of idiopathic unicentric CD was made based upon histological examination, which demonstrated the pathological features of CD of mixed type, including hyperplasia of follicular lymphoids with abundant plasma cells, degenerative germinal centers, interfollicular vascularity and hyaline degeneration. The diagnosis was corroborated by immunohistochemical analysis which detected multiple biomarkers. CONCLUSION: This is the first study that describes the clinicopathological features of CD presenting with jaundice, which may deepen and extend our understanding of this disease.

Role of piwi-interacting RNA-651 in the carcinogenesis of non-small cell lung cancer.

Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines. However, the role of piRNAs in carcinogenesis has not been clearly defined. In the present study, a small interfering RNA inhibitor of piR651 was transfected into the NSCLC A549 and HCC827 cell lines to evaluate the effect of piR651 on cell growth. The association between piR651 expression and apoptosis was evaluated by flow cytometry and western blot analysis. Wound-healing and Transwell migration and invasion assays were used to determine the effect of piR651 on the migration and invasion of NSCLC cell lines. The results revealed that inhibition of piR651 inhibited cell proliferation and significantly increased the apoptotic rate compared with the negative control (NC), as well as altering the expression of apoptosis-associated proteins. There were fewer migrating and invading cells in the piR651-inhibited group than in the NC group in the Transwell assays. Furthermore, in the wound-healing assay, the wound remained wider in the piR651 inhibitor group, suggesting decreased cell migration compared with that in the NC group. The results of the present study demonstrate that piR651 potentially regulates NSCLC tumorigenic behavior by inhibiting cell proliferation, migration and invasion and by inducing apoptosis. Therefore, piR651 is a potential cancer diagnosis marker.

Percutaneous vertebroplasty versus conservative treatment for osteoporotic vertebral compression fractures: An updated meta-analysis of prospective randomized controlled trials.

BACKGROUND: This meta-analysis of Randomized Controlled Trials (RCTs) aims to evaluate the efficacy and safety in percutaneous vertebroplasty (PVP) and conservative treatment (CT) for osteoporotic vertebral compression fractures (OVCFs). METHODS: The authors searched RCTs in electronic databases (Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Medline, Embase, Springer Link, Web of Knowledge, OVID and Google Scholar) in a timeframe from their establishment to Feb 2017. We also manually searched the reference lists of reports and reviews for possible relevant studies. Researches on PVP versus CT in OVCFs were selected in this meta-analysis. The quality of all studies was assessed and effective data were pooled for this meta-analysis. The outcomes were measured by pain relief (one week, one month, three months and six months), quality of life (RDQ, ED-5Q and QUALEFFO) and the rate of adjacent vertebral fracture. Publication bias assessment was also performed, respectively. The meta-analysis was performed using RevMan 5.1. RESULTS: 13 reports (12 RCTs) with a total 1231 patients (623 in the PVP and 608 in the CT) met inclusion criteria. Patients were followed up for at least 2 weeks in all the studies. Statistical differences were found between pain relief (one week (MD 1.36, 95% CI (0.55, 2.17)), one month (MD 1.56, 95% CI (0.43, 2.70)) and six months (MD -1.59, 95% CI (-2.9, -0.27))) and QUALEFFO (MD -5.03 95%CI (-7.94, -2.12)). No statistical differences were found between pain relief (three months (MD -0.28, 95% CI (-1.46, 0.90))), RDQ (MD -0.59, 95% CI (-1.31, 0.13)), ED-5Q (MD 0.10, 95% CI (-0.01, 0.22)) and the rate of adjacent vertebral fracture (RR 1.21, 95% CI (0.89, 1.62)). CONCLUSIONS: PVP is associated with higher pain relief than CT in the early period. Furthermore, PVP did not increase the rate of adjacent vertebral fracture. The results indicate that it is a safe and effective treatment for OVCFs. Because of some limitations, these findings should be interpreted with caution. Additional studies are needed. Large, definitive RCTs are needed.

Locking compression plate distal ulna hook plate fixation versus intramedullary screw fixation for displaced avulsion fifth Metatarsal Base fractures: a comparative retrospective cohort study.

BACKGROUND: Intramedullary screw (IMS) fixation was wildly used in fifth metatarsal base fractures (FMBFs) and the results were satisfactory. However, in the comminuted osteoporosis or small displaced avulsion FMBFs, anatomical reduction and stable fixation could not be achieved with IMS. The Locking Compression Plate (LCP) distal ulna hook plate fixation was a novel alternative fixation method. The aim of this retrospective cohort study was to determine if LCP distal ulna hook plate fixation resulted in improved outcomes compared to the traditional IMS fixation in displaced avulsion FMBFs. METHODS: Of 43 patients with displaced avulsion FMBFs, 18 patients were treated with LCP distal ulna hook plate fixation and 25 were treated with IMS fixation. The patients were evaluated clinically and radiographically and followed up to 12 months. The surgery time, time for hospital stay, time for weight-bearing, time for bony union, time for return to daily life, pain relief, functional outcome and complications after treatment with LCP distal ulna hook plate fixation or IMS fixation were compared. The functional outcome was assessed by the AOFAS (American Orthopedic Foot and Ankle Society) mid-foot score at 3, 6, 9, and 12 months after surgery. Meanwhile, pain scores were obtained at 3, 6, 9, and 12 months after surgery. RESULTS: The two cohorts had similar baseline characteristics. Surgery time was less in LCP distal ulna hook plate fixation cohort compare to IMS fixation cohort (p < 0.0001). Time for partial weight-bearing (p < 0.0001) and full weight-bearing (p < 0.0001) also demonstrated significant improvements in patients with LCP distal ulna hook plate fixation compared to IMS fixation. Patients in the LCP distal ulna hook plate fixation cohort had significantly increased AOFAS at 9 months (p < 0.0001) and 12 months (p < 0.0001) after surgery compared to the IMS fixation cohort. CONCLUSION: In this retrospective cohort study, LCP distal ulna hook plate fixation as an alternative fixation method was better therapy for the displaced avulsion FMBFs compared to IMS fixation. LCP distal ulna hook plate fixation had a short surgery time and improved functional performance.

Gene expression profile after knockdown of USP18 in Hepg2.2.15 cells.

In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2.2.15 stably expressing USP18-shRNA cells versus control cells using the Affymetrix Human Transcriptome Array (HTA) 2.0 microarrays. Microarray analysis indicated that genes involved in regulation of thyroid hormone signaling pathway, complement, and coagulation cascades, PERK-mediated unfolded protein response, and insulin-like growth factor-activated receptor activity were significantly altered after USP18 knockdown for 72 h. Furthermore, genes involved in hepatocyte proliferation, liver fibrosis, such as cell cycle regulatory gene CCND1, were also altered after USP18 knockdown in Hepg2.2.15 cells. In conclusion, USP18 is critical for regulating the replication of HBV in Hepg2.2.15 cells, which suggest that USP18 may be a candidate target for HBV treatment.

[Microbial Population Dynamics During Sludge Granulation in a Simultaneous Nitrogen and Phosphorus Removal System].

In this study, domestic sewage was utilized to cultivate aerobic granular sludge (AGS) in a simultaneous nitrogen and phosphorus removal (SNPR) system. The bacterial population dynamics during the aerobic sludge granulation were investigated to reveal the granulation mechanisms using Illumina MiSeq PE300 high-throughput sequencing. Quantitative real time polymerase chain reactions (PCR) were used to investigate shifts in the abundance of ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), nitrite-oxidizing bacteria (NOB) and polyphosphate accumulating organisms (PAOs). After cultivation for 100 d, the AGS was compact and demonstrated good SNPR performance. During the AGS formation process, extracellular polysaccharides obviously increased, while extracellular proteins kept relatively stable. The abundance of AOA significantly decreased during the formation of AGS process, while the abundance of PAOs increased. The bacterial diversity increased at first and then decreased during the formation of AGS. The bacterial community changed dramatically during aerobic sludge granulation. Persistent operational taxonomic units (OTUs) accounted for 92.70% of the total sequences. Proteobacteria (31.07%-53.67%), Bacteroidetes (6.70%-16.50%) and Chloroflexi (7.84%-13.36%) were the dominant phyla. Candidatus competibacter was obviously enriched in the AGS formation process (increased from 0.11% in the seed sludge to 35.33% in the AGS) and may play an important role in the formation of AGS.

Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling.

Ubiquitin-specific protease 18 (USP18, also known as UBP43) has both interferon stimulated gene 15 (ISG15) dependent and ISG15-independent functions. By silencing the expression of USP18 in HepG2.2.15 cells, we studied the effect of USP18 on the anti-HBV activity of IFN-F and demonstrated that knockdown of USP18 significantly Inhibited the HBV expression and increased the expression of ISGs. Levels of hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), HBV DNA and intracellular hepatitis B virus core antigen (HBcAg) were dramatically decreased with or without treatment of indicated dose of IFN-F. Suppression of USP18 activated the JAK/STAT signaling pathway as shown by the increased and prolonged expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) in combination with enhanced expression of several interferon stimulated genes (ISGs). Our results indicated that USP18 modulates the anti-HBV activity of IFN-F via activation of the JAK/STAT signaling pathway in Hepg2.2.15 cells.

piR-651 and its function in 95-D lung cancer cells.

PIWI-associated RNAs (piRNAs or piRs), a new-found class of small non-coding RNAs, which are mainly expressed in germline cells and partly in somatic lines, have a vital role in carcinogenesis by maintaining genomic integrity and regulation of epigenetics. The previous studies have confirmed that the expression of piR-651 is upregulated in several cancer tissue and cell lines, including lung cancer. However, the mechanism of carcinogenesis and piR-651 remains to be elucidated. Therefore, the present study assessed the 95-D high metastasis human lung cancer cell line to detect the effect of piR-651 on carcinogenesis. Firstly, piR-651 promoted the high metastasis characteristic of the 95-D cell lines by Transwell and wound-healing assays. The influence of piR-651 on tumor cell proliferation and apoptosis was detected by the MTT assay and flow cytometry. In conclusion, piR-651 may be an oncogene in lung cancer formation and development. Therefore, piR-651 regulated carcinogenesis by influencing cell proliferation, apoptosis, migration and invasion, and may be a potential tumor marker and therapeutic target.

MicroRNAs in osteosarcoma.

Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity that principally emerges in children and adolescents. Presently, the prognosis of OS patients remains poor due to resistance to chemotherapy, highlighting the need for new therapeutic approaches. MicroRNAs (miRNAs), a class of small noncoding RNA molecules, can negatively modulate protein expression at the post-transcriptional level. miRNAs regulate a variety of normal physiologic processes and are involved in tumorigenesis and development of multiple malignancies, including OS. Some miRNAs are differentially expressed in OS tissues, cell lines and serum, and have been shown to correlate with the malignant phenotype and prognosis. These altered miRNAs function as oncogenes or tumor suppressor genes in this process. Moreover, restoration of miRNA expression has shown promise for the treatment of OS. Here, we describe miRNA biochemistry with a focus on expression profile, role and therapeutic potential in OS. A better understanding will facilitate the identification and characterization of novel biomarkers and development of miRNA-targeted therapies.

[Surgical treatment of primary hyperparathyroidism].

OBJECTIVE: To investigate the causes of misdiagnosis and the surgical treatment of primary hyperparathyroidism (PHPT). METHODS: The clinical data of 26 patients with PHPT from July 2008 to January 2013 in The Affiliated Hospital of Chengde Medical College and The Fourth Hospital of Hebei Medical University were retrospectively analyzed, including preoperative diagnosis and operative method. The level of serum calciumion and serum parathyroid hormone (PTH), Ultrasonography, CT, (99)mTc-methoxy isobutylis onitrile ((99)mTc-MIBI) were used in the diagnosis before operation. All patients accepted surgical treatment after the level of serum calciumion decreased to normal. RESULTS: The level of PTH was examined 10 min after resection, which declined more than 50%. After pathological examination, 23 cases were diagnosed as parathyroid adenoma, 2 cases were parathyroid hyperplasia, and 1 case was parathyroid carcinoma. The level of serum calciumion and serum parathyroid hormone were returned to the normal level after operation. All patients recovered with no postoperative complication.Followed up lasted from 6 months to 5 years, no case recurred.Sixteen cases with symptoms experienced significant improvement in signs, including 10 cases with clinical symptoms completely disappeared. CONCLUSIONS: The test of serum calciumion and serum PTH, Ultrasonography, CT, (99)mTc-MIBI are helpful to reduce the misdiagnose rate of primary hyperparathyroidism before operation. The examination of serum parathyroid hormone in operation is helpful to reduce the operation range and time.

Polymorphisms in luteinizing hormone receptor and hypothalamic gonadotropin-releasing hormone genes and their effects on sperm quality traits in Chinese Holstein bulls.

Genes of hypothalamic-pituitary-gonadal axis play a key role in male reproductive performance. This study evaluated the polymorphisms of luteinizing hormone receptor (LHR) and hypothalamic gonadotropin-releasing hormone (GnRH) genes and their effects on sperm quality traits including semen volume per ejaculate (VOL), sperm density (SD), fresh sperm motility (FSM), thawed sperm motility (TSM), acrosome integrity rate (AIR), and abnormal sperm rate (ASR) collected from 205 Chinese Hostein bulls. The study bulls consisted of 205 mature Chinese Holstein, 27 Simmental, 28 Charolais, and 14 German yellow cattle. One single nucleotide polymorphism (SNP) (A883G) in exon 2 of GnRH and two SNPs (A51703G and G51656T) in intron 9 of LHR were identified in 274 bulls. Analysis of variance in 205 Chinese Holstein bulls showed that age had significant effect on both SD and FSM (P < 0.01), and ASR (P < 0.05). With regards to genotype and its interaction with age, only the SNP of G51656T in LHR gene had significant effect on SD (P < 0.05, P < 0.01; respectively). The association result showed that bulls with AG genotype had higher FSM than bulls with AA and GG genotype in LHR at 51,703 locus (P < 0.10), and bulls with GG genotype had higher SD than bulls with TT genotype in LHR at G51656T locus (P < 0.10). Phenotypic correlation among the traits revealed that significant negative correlations were observed between ASR and AIR (r = -0.736, P < 0.01), ASR and AIR (r = -0.500, P < 0.01). There were moderate positive correlations between VOL and SD (r = 0.422, P < 0.01), as well as FSM (r = 0.411, P < 0.01). In conclusion, LHR may be a potential marker for sperm quality of SD and FSM.

[Effect of sildenafil on ABR thresholds shift to noise-induced hearing loss in guinea pigs].

OBJECTIVE: To investigate the protective effects of sildenafil to noise-induced hearing loss in guinea pigs. METHODS: Guinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, with 10 in each group. One week after the exposure of 110 dB (A) white noise, sildenafil [10 mg/(kg×d)] and normal saline [4 ml/(kg×d)] were injected into guinea pigs of noise plus sildenafil group (NSG) and noise plus normal saline group(NNG) respectively. One week after noise exposure to four weeks continuous administration. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise, 1, 2 and 4 weeks post-drugs. The changes of cochlea hair cells were also observed by scanning electron microscope (SEM). RESULTS: After noise exposure, the ABR threshold shifts in NSG were significantly fewer than that in the NNG. An average of 19.1 dB in NNG compared with 19.8 dB in NSG. Four weeks after exposure, the threshold shifts were become larger to 22.0 dB in NNG while become smaller to 4.8 dB in NSG. Compared NNG with NSG, in addition to noise exposure time point, there were statistically significant differences in the rest time points after administration of the ABR threshold (P<0.05). SEM showed that the inner and outer hair cells in NNG displayed mess, fusion and imperfections. In NSG, the hair cells displayed slight pathological changes, there was no significant difference when compared with control group. CONCLUSION: Sildenafil is able to reduce the ascending of ABR thresholds shift, and it can significantly protect against noise-induced hearing loss.

Effects of raspberry phytochemical extract on cell proliferation, apoptosis, and serum proteomics in a rat model.

The red raspberry extract possesses potent antioxidant capacity and anticancerous activity in vitro and in vivo. The objective of this study was to determine whether red raspberry extract affected the cell cycle, angiogenesis, and apoptosis in hepatic lesion tissues from a rat model induced by diethylnitrosamine (DEN) as well as changes of serum proteomics. Rats were treated with red raspberry extract (0.75, 1.5, or 3.0 g/kg of body weight) by gavage starting 2 h after DEN administration and continued for 20 wk. Red raspberry extract inhibited cell proliferation, vascular endothelial growth factor VEGF expression, and induced apoptosis in the hepatic lesion tissues. In addition, 2 protein peaks (2597.93 and 4513.88 m/z) were identified to differentially express in the 3.0 g/kg body weight and positive control groups by serum proteomics. These results suggest that a dietary supplement with red raspberry effectively protects against chemically induced hepatic lesions in rats.

Fresh raspberry phytochemical extract inhibits hepatic lesion in a Wistar rat model.

BACKGROUND: Red raspberry possesses potent antioxidant capacity and antiproliferative activity against cancer in vitro. METHODS: The objective of this study was to determine the protective effects of raspberry 80% acetone extract in a rat hepatic lesions model induced by diethylnitrosamine (DEN). Rats were treated with the red raspberry extract (0.75, 1.5 or 3.0 g/kg of body weight) by gavage starting 2 h after DEN administration and continuing for 20 weeks. RESULTS: A dose-dependent inhibition by red raspberry extract of DEN-induced hepatic nodule formation which stands for hepatic lesions was observed. Corresponding hepatic nodule incidence rates were 45.0, 40.0, 25.0 and 5.0% in positive control, low, middle and high groups, respectively (P < 0.01 or 0.05). Gross findings, histopathological and ultrastructural evaluations of hepatic lesion were performed on 9, 8, 5 and 1 hepatic nodule in positive control, low, middle and high doses of groups, respectively, identified in rats from the respective groups of 20. A decreasing trend of proportions of hepatocellular carcinoma masses accompanied the increasing doses of red raspberry extract. CONCLUSIONS: These findings demonstrate that the potent capacity of red raspberry diet could not only suppress DEN-induced hepatic lesions in rats, but also reduce the definite diagnostic features of neoplasm.

Differential expression of proteomics models of colorectal cancer, colorectal benign disease and healthy controls.

BACKGROUND: Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. The hypersensitive analytical technique of proteomics can detect molecular changes before the tumor is palpable. The surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS) is a newly-developed technique of evaluating protein separation in recent years. The protein chips have established the expression of tumor protein in the serum specimens and become the newly discovered markers for tumor diagnosis. The objective of this study was to find new markers of the diagnosis among groups of CRC, colorectal benign diseases (CBD) and healthy controls. The assay of SELDI-TOF-MS with analytical technique of protein-chip bioinformatics was used to detect the expression of protein mass peaks in the sera of patients or controls. One hundred serum samples, including 52 cases of colorectal cancer, 27 cases of colorectal benign disease, and 21 cases of healthy controls, were examined by SELDI-TOF-MS with WCX2 protein-chips. RESULTS: The diagnostic models (I, II and III) were setup by analyzed the data and sieved markers using Ciphergen - Protein-Chip-Software 5.1. These models were combined with 3 protein mass peaks to discriminate CRC, CBD, and healthy controls. The accuracy, the sensitivity and the particularity of cross verification of these models are all highly over 80%. CONCLUSIONS: The SELDI-TOF-MS is a useful tool to help diagnose colorectal cancer, especially during the early stage. However, identification of the significantly differentiated proteins needs further study.