Reduced long noncoding RNA PGM5-AS1 facilitated proliferation and invasion of colorectal cancer through sponging miR-100-5p.

OBJECTIVE: We aimed at investigating the expression of Long non-coding RNA (LncRNA) PGM5-AS1 and its facilitating effects on proliferation and invasion of colorectal cancer by sponging miR-100-5p. PATIENTS AND METHODS: qRT-PCR was performed to detect the expressions of PGM5-AS1 and SMAD4 in human colorectal cancer tissues and cells. CCK-8 assay was performed to evaluate the SW403 cells proliferation and transwell assay was performed to evaluate the SW403 cells migration. The correlation between miR-100-5p and PGM5-AS1 was detected by statistical analysis. Bioinformatics prediction and Luciferase assay were performed to explore the interaction and binding site of PGM5-AS1 and miR-100-5p, miR-100-5p and SMAD4, respectively. RESULTS: We found that both PGM5-AS1 and SMAD4 were downregulated in human colorectal cancer tissues and cells. qRT-PCR and CCK-8 assay showed that PGM5-AS1 expression is associated with the proliferation of colorectal cancer cells. Transwell assay showed that PGM5-AS1 regulated the migration ability of colorectal cancer cells. The bioinformatics prediction and Luciferase assay demonstrated that by sponging miR-100-5p, PGM5-AS1 can serve as a molecular sponge to further regulate the expression of SMAD4. CONCLUSIONS: In this study, we found that lncRNA-PGM5-AS1 was low expressed in human colorectal cancer cells, which could promote tumor proliferation, migration and invasion by serving as a molecular sponge and by modulating the inhibitory effect of miR-100-5p on tumor suppressor gene SMAD4.

Clinical label-free biochemical and metabolic fluorescence lifetime endoscopic imaging of precancerous and cancerous oral lesions.

INTRODUCTION: Incomplete head and neck cancer resection occurs in up to 85% of cases, leading to increased odds of local recurrence and regional metastases; thus, image-guided surgical tools for accurate, in situ and fast detection of positive margins during head and neck cancer resection surgery are urgently needed. Oral epithelial dysplasia and cancer development is accompanied by morphological, biochemical, and metabolic tissue and cellular alterations that can modulate the autofluorescence properties of the oral epithelial tissue. OBJECTIVE: This study aimed to test the hypothesis that autofluorescence biomarkers of oral precancer and cancer can be clinically imaged and quantified by means of multispectral fluorescence lifetime imaging (FLIM) endoscopy. METHODS: Multispectral autofluorescence lifetime images of precancerous and cancerous lesions from 39 patients were imaged in vivo using a novel multispectral FLIM endoscope and processed to generate widefield maps of biochemical and metabolic autofluorescence biomarkers of oral precancer and cancer. RESULTS: Statistical analyses applied to the quantified multispectral FLIM endoscopy based autofluorescence biomarkers indicated their potential to provide contrast between precancerous/cancerous vs. healthy oral epithelial tissue. CONCLUSION: To the best of our knowledge, this study represents the first demonstration of label-free biochemical and metabolic clinical imaging of precancerous and cancerous oral lesions by means of widefield multispectral autofluorescence lifetime endoscopy. Future studies will focus on demonstrating the capabilities of endogenous multispectral FLIM endoscopy as an image-guided surgical tool for positive margin detection during head and neck cancer resection surgery.

Performance of BAC for DBPs precursors' removal for one year with micro-polluted lake water in East-China.

Effectiveness of biological activated carbon (BAC) filter in removing disinfection byproducts (DBPs) precursors of micro-polluted lake water for one year was conducted. The formation potential (FP) of DBPs (trihalomethanes (THMs), haloacetic acids (HAAs) and Nitrosamines (NAs)), dissolved organic carbon (DOC), molecular weight (MW) distribution and excitation emission matrix fluorescence (EEM) of dissolved organic material (DOM) in the influent and effluent of BAC were determined. The results indicated that the removal efficiency (RE) of DOC ranged from 42.9-28.3%. Neither virgin GAC nor long-term operated BAC could efficiently dispose of THMs and HAAs precursors (RE from 35.2-18.8%, from 42 to 8.4%, respectively), however, BAC still showed good ability in removal of NAs precursors after a year operation, of which RE just dropped from 81.7-69.6%. There was strong correlation between RE of NAs precursors and DOC with small MW (<0.5 kDa). The removal of HAAs precursors showed relatively close relation to aromatic protein-like components and soluble microbial pollutants (SMPs). Weak direct relationship was found between the water quality parameters and THMs precursors.

Chronic periodontitis can affect the levels of potential oral cancer salivary mRNA biomarkers.

BACKGROUND AND OBJECTIVE: More than 100 salivary constituents have been found to show levels significantly different in patients with oral squamous cell carcinoma (OSCC) from those found in healthy controls, and therefore have been suggested to be potential salivary biomarkers for OSCC detection. However, many of these potential OSCC salivary biomarkers are also involved in chronic inflammation, and whether the levels of these biomarkers could be affected by the presence of chronic periodontitis was not known. The objective of this pilot study was therefore to measure the levels of seven previously reported potential OSCC salivary mRNA biomarkers in patients with chronic periodontitis and compare them to levels found in patients with OSCC and healthy controls. The seven salivary mRNAs were interleukin (IL)-8, IL-1ß, dual specificity phosphatase 1, H3 histone family 3A, ornithine decarboxylase antizyme 1, S100 calcium-binding protein P (S100P) and spermidine/spermine N1-acetyltransferase 1. MATERIAL AND METHODS: Unstimulated whole saliva samples were collected from a total of 105 human subjects from the following four study groups: OSCC; CPNS (chronic periodontitis, moderate to severe degree, non-smokers); CPS (chronic periodontitis, moderate to severe degree, smokers); and healthy controls. Levels of each mRNA in patient groups (OSCC or chronic periodontitis) relative to the healthy controls were determined by a pre-amplification reverse transcription-quantitative polymerase chain reaction approach with nested gene-specific primers. Results were recorded and analyzed by the Bio-Rad CFX96 Real-Time System. Mean fold changes between each pair of patient vs. control groups were analyzed by the Mann-Whitney U-test with Bonferroni corrections. RESULTS: Only S100P showed significantly higher levels in patients with OSCC compared to both patients with CPNS (p = 0.003) and CPS (p = 0.007). The difference in S100P levels between patients with OSCC and healthy controls was also marginally significant (p = 0.009). There was no significant difference in the levels of salivary IL-8, IL-1ß and dual specificity phosphatase 1 mRNAs between patients with OSCC and patients with CPNS (p = 0.510, 0.058 and 0.078, respectively); no significant difference in levels of salivary ornithine decarboxylase antizyme 1 and spermine N1-acetyltransferase mRNAs between patients with OSCC and patients with CPS (p = 0.318 and 0.764, respectively); and no significant difference in levels of the H3 histone family 3A mRNA between patients with OSCC and either CPS (p = 0.449) or healthy controls (p = 0.107). CONCLUSIONS: Salivary S100P mRNA could be a reliable biomarker for OSCC detection, regardless of the presence of chronic periodontitis. The presence of chronic periodontitis could significantly affect the levels of the other six mRNAs, and negatively influence reliability for using them as biomarkers for oral cancer detection.

Application of levator veli palatini retropositioning combined with Buccinator myomucosal island flap for congenital cleft palate.

Congenital cleft palate causes a serious obstacle to children with regard to language and eating function. The aim of the current study was to examine the clinical application of a type of palatoplasty that has a reduced impact on the maxillary growth and good function in velopharyngeal competence. A total of 37 patients with cleft palate were treated with levator veli palatini retropositioning combined with Buccinator myomucosal island flap. The patients were successfully treated in the first phase and were followed up for 1-3 years. Speech intelligibility was satisfactory and no fistula occurred. In conclusion, the results suggested that levator veli palatini retropositioning combined with the Buccinator myomucosal island flap may restore normal anatomic structure and location of the levator veli palatini, obtain good velopharyngeal competence, and decrease the incidence rate thereof. Thus, levator veli palatini retropositioning combined with the Buccinator myomucosal island flap is a functional procedure for cleft palate repair.

Comparison of through-the-scope stent insertion with standard stent insertion for the management of malignant colorectal obstruction: a prospective study.

BACKGROUND: The aim of the present study was to compare the feasibility, safety and efficacy of the through-the-scope (TTS) stent technique to that of the standard metallic stent technique for the management of malignant colorectal obstruction. METHODS: Fifty-two patients scheduled to receive stent insertion for the management of acute obstructive colorectal cancer were enrolled in our study and divided into a TTS stent group (n = 24) and a standard stent group (n = 28). The stent insertion procedure was performed under endoscopic and fluoroscopic guidance in all patients. The success rate, complications, fluoroscopic time, and clinical remission rate were recorded and compared. RESULTS: The technique success rate was 100 % (24/24) in the TTS stent group and 78.6 % (22/28) in the standard stent group (p = 0.03). In five patients in the standard stent group, the stent failed to pass through occlusive lesions because of the stiffness of the stent system. Serious bleeding occurred in one patient in the standard stent group. The fluoroscopy time in the TTS stent group was significantly reduced (12.9 ± 6.6 min) compared with that of the standard stent group (24.8 ± 9.8 min; p < 0.01). Silent perforation occurred in 17.9 % (5/28) of the cases in the standard stent group compared with none in the TTS (p = 0.03). Clinical remission was achieved in 97.1 % (23/24) and 78.6 % (22/28) of patients in the TTS and standard stent groups, respectively (p = 0.11). CONCLUSIONS: The TTS stent is safer and more feasible for the management of malignant colorectal obstructions than the standard stent, and the TTS technique provides a higher success rate, a similar clinical remission rate, and a markedly reduced fluoroscopic time.

Positron emission tomography (18)F-fluorodeoxyglucose uptake and prognosis in patients with bone and soft tissue sarcoma: A meta-analysis.

PURPOSE: To investigate the prognostic significance of (18)F-FDG PET imaging in patients with bone and soft tissue sarcoma, a meta-analysis was conducted. METHODS: Comprehensive literature searches were performed in PubMed, Embase, Web of Science and Cochrane Library. Pooled hazard ratio (HR) values were calculated to assess the correlations of pre-chemotherapy SUV (SUV1), post-chemotherapy SUV (SUV2), SUV Ratio, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with event-free survival (EFS) and overall survival (OS). RESULTS: Twenty-three studies with 1261 patients were identified. The combined HRs for EFS were 1.84 (95% CI: 1.54-2.20) for SUV1, 2.92 (95% CI: 2.15-3.97) for SUV2, 1.90 (95% CI: 1.43-2.52) for SUV Ratio, 3.01 (95% CI: 1.36-6.67) for TLG and 2.32 (95% CI: 1.44-3.75) for MTV. The pooled HRs for OS were 1.85 (95% CI: 1.49-2.30) for SUV1, 2.00 (95% CI: 1.39-2.88) for SUV2, 2.20 (95% CI: 1.18-4.10) for SUV Ratio, 6.19 (95% CI: 2.17-17.66) for TLG and 2.67 (95% CI: 1.52-4.68) for MTV. Besides, high SUV1 was found to be significantly associated with higher rate of metastasis (RR 5.55, 95% CI: 2.75-11.18) and local recurrence (RR 1.87 95% CI: 1.28-2.72). CONCLUSION: (18)F-FDG PET parameters of SUV1, SUV2, SUV Ratio, TLG and MTV may have effective prognostic significance for patients with bone and soft tissue sarcoma. (18)F-FDG PET imaging may be a promising tool to help predict survival outcomes of these patients.

Factors Affecting the Incidence of Angel Wing in White Roman Geese: Stocking Density and Genetic Selection.

The present study investigated stocking density and genetic lines, factors that may alter the severity and incidence of angel wing (AW), in White Roman geese. Geese (n = 384) from two genetically selected lines (normal- winged line, NL, and angel-winged line, AL, respectively) and one commercial line (CL) were raised in four pens. Following common commercial practice, low-stocking-density (LD), medium-stocking-density, and high-stocking-density treatments were respectively administered to 24, 32, and 40 geese per pen at 0 to 3 weeks (1.92 m(2)/pen) and 4 to 6 weeks (13.2 m(2)/pen) of age and to 24, 30, and 36 geese at 7 to 14 weeks (20.0 m(2)/pen) of age. The results revealed that stocking density mainly affected body weight gain in geese younger than 4 weeks, and that geese subjected to LD had a high body weight at 2 weeks of age. However, the effect of stocking density on the severity score of AW (SSAW) and incidence of AW (IAW) did not differ significantly among the treatments. Differences were observed among the genetic stocks; that is, SSAW and IAW were significantly higher in AL than in NL and CL. Genetic selection generally aggravates AW, complicating its elimination. To effectively reduce IAW, stocking density, a suspected causal factor, should be lower than that presently applied commercially.

Modal analysis and efficient coupling of TE01 mode in small-core THz Bragg fibers.

We report a design of low-loss THz Bragg fibers with a core size on the order of wavelength that operates near the cutoff frequency of its TE01 mode. We also propose a broadband Y-type mode converter based on branched rectangular metallic waveguides to facilitate coupling between the TE01 mode of the Bragg fiber and the TEM mode in free space with 60% efficiency. Our fiber holds strong promise to facilitate beam-wave interaction in gyrotron for high-efficiency THz generation.

Selection for Duration of Fertility and Mule Duck White Plumage Colour in a Synthetic Strain of Ducks (Anas platyrhynchos).

A synthetic strain of ducks (Anas platyrhynchos) was developed by introducing genes for long duration of fertility to be used as mother of mule ducklings and a seven-generation selection experiment was conducted to increase the number of fertile eggs after a single artificial insemination (AI) with pooled Muscovy semen. Reciprocal crossbreeding between Brown Tsaiya LRI-2 (with long duration of fertility) and Pekin L-201 (with white plumage mule ducklings) ducks produced the G0. Then G1 were intercrossed to produce G2 and so on for the following generations. Each female duck was inseminated 3 times, at 26, 29, and 32 weeks of age. The eggs were collected for 14 days from day 2 after AI. Individual data regarding the number of incubated eggs (Ie), the number of fertile eggs at candling at day 7 of incubation (F), the total number of dead embryos (M), the maximum duration of fertility (Dm) and the number of hatched mule ducklings (H) with plumage colour were recorded. The selection criterion was the breeding values of the best linear unbiased prediction animal model for F. The results show high percentage of exhibited heterosis in G2 for traits to improve (19.1% for F and 12.9% for H); F with a value of 5.92 (vs 3.74 in the Pekin L-201) was improved in the G2. Heritabilities were found to be low for Ie (h (2) = 0.07±0.03) and M (h (2) = 0.07±0.01), moderately low for Dm (h (2) = 0.13±0.02), of medium values for H (h (2) = 0.20±0.03) and F (h (2) = 0.23±0.03). High and favourable genetic correlations existed between F and Dm (rg = 0.93), between F and H (rg = 0.97) and between Dm and H (rg = 0.90). The selection experiment showed a positive trend for phenotypic values of F (6.38 fertile eggs in G10 of synthetic strain vs 5.59 eggs in G4, and 3.74 eggs in Pekin L-201), with correlated response for increasing H (5.73 ducklings in G10 vs 4.86 in G4, and 3.09 ducklings in Pekin L-201) and maximum duration of the fertile period without increasing the embryo mortality rate. The average predicted genetic response for F was 40% of genetic standard deviation per generation of selection. The mule ducklings' feather colour also was improved. It was concluded that this study provided results for a better understanding of the genetics of the duration of fertility traits in the common female duck bred for mule and that the selection of a synthetic strain was effective method of improvement.

Elevated CO2 concentration impacts cell wall polysaccharide composition of green microalgae of the genus Chlorella.

UNLABELLED: The effect of CO2 concentration on the relative content of starch, lipid and cell wall carbohydrates in microalgal biomass was investigated for the four following Chlorella strains: C. vulgaris (UTEX 259), C. sorokiniana (UTEX 2805), C. minutissima (UTEX 2341) and C. variabilis (NC64A). Each strain had a different response to CO2 concentration. The starch content was higher in UTEX259 and NC64A cultured with 2% CO2 in the air supply than in cells cultured with ca. 0·04% CO2 (ambient air), while starch content was not affected for UTEX 2805 and UTEX 2341. The lipid content was higher in Chlorella minutissima UTEX 2341 cultured in 2% CO2 than in cells cultured in ambient air, but was unchanged for the other three strains. All four Chlorella strains tended to have a higher percentage of uronic acids and lower percentage of neutral sugars in their cell wall polysaccharide complement when grown with 2% CO2 supply. Although the percentage of neutral sugars in the cell walls varied with CO2 concentration, the relative proportions of different neutral sugar constituents remained constant for both CO2 conditions. The results demonstrate the importance of considering the effects of CO2 on the cell wall carbohydrate composition of microalgae. SIGNIFICANCE AND IMPACT OF THE STUDY: Microalgae have the potential to produce products that will reduce society's reliance on fossil fuels and address challenges related to food and feed production. An overlooked yet industrially relevant component of microalgae are their cell walls. Cell wall composition affects cell flocculation and the recovery of intracellular products. In this study, we show that increasing CO2 level results in greater cell wall polysaccharide and uronic acid content in the cell walls of three strains of microalgae. The results have implications on the management of systems for the capture of CO2 and production of fuels, chemicals and food from microalgae.

Complex hemodynamic insult in combination with wall degeneration at the apex of an arterial bifurcation contributes to generation of nascent aneurysms in a canine model.

BACKGROUND AND PURPOSE: The detailed mechanisms of cerebral aneurysm generation remain unclear. Our aim was to investigate whether specific hemodynamic insult in combination with arterial wall degeneration leads to the development of aneurysms in a canine model. MATERIALS AND METHODS: New branch points in the common carotid artery were created in 18 dogs. Nine animals subsequently received elastase insult at the arterial bifurcation apex (elastase-treated bifurcation group); the control bifurcation group (n=9) received saline, and 3 dogs received an elastase insult to both straight common carotid arteries (elastase-treated straight group). Angiographic and hemodynamic analysis was performed immediately and 12 and 24 weeks' postsurgery; histologic response was evaluated at 12 and 24 weeks. RESULTS: Angiography revealed nascent aneurysms (mean, 3.2±0.4 mm) at the arterial bifurcation apices in 5/9 models of the elastase-treated bifurcation group (versus 0 in the control bifurcation group and elastase-treated straight group) without any observed aneurysm rupture. Histologic analysis revealed internal elastic lamina discontinuity, elastic fiber disruption, a thinner muscular layer, reduced smooth-muscle cell proliferation, increased inflammatory cell (macrophage) infiltration, and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the media of the elastase-treated bifurcation group compared with that in either the control bifurcation group or the elastase-treated straight group (P<.001). Hemodynamic analysis after surgery indicated that the apex experienced extremely low wall shear stress and flow velocity and the highest relative and total pressure in the elastase-treated bifurcation group, while the values returned to normal after arterial wall remodelling. CONCLUSIONS: In our study, combined hemodynamic insult and arterial wall degeneration at arterial bifurcations are required for the generation of aneurysms in a canine model.

Genomewide Study of Salivary MicroRNAs for Detection of Oral Cancer.

MicroRNAs (miRNAs) in human saliva have recently demonstrated to be potential biomarkers for diagnosis purposes. However, lack of well-characterized/matched clinical groups and lack of suitable endogenous control (EC) for salivary extracellular miRNA detection and normalization are among the restrictions of applying salivary-based miRNA biomarker discovery. In the present study, we examined the differential expression pattern of miRNAs among 4 groups of subjects-including patients with oral squamous cell carcinoma (OSCC), patients with OSCC in remission (OSCC-R), patients with oral lichen planus, and healthy controls (HCs)-using a genomewide high-throughput miRNA microarray. First, we systematically screened 10 pooling samples and 34 individual samples of different groups to find a proper EC miRNA. We then investigated the genomewide expression patterns of differentially expressed miRNAs in saliva of different groups using NanoString nCounter miRNA expression assay and real-time quantitative polymerase chain reaction, followed by construction of receiver operating characteristic curves to determine the sensitivity and specificity of the assay. We identified miRNA-191 as a suitable EC miRNA with minimal intergroup and intragroup variability, and we used it for normalization. Of more than 700 miRNAs tested, 13 were identified as being significantly deregulated in saliva of OSCC patients compared to HCs: 11 miRNAs were underexpressed (miRNA-136, miRNA-147, miRNA-1250, miRNA-148a, miRNA-632, miRNA-646, miRNA668, miRNA-877, miRNA-503, miRNA-220a, miRNA-323-5p), and 2 miRNAs were overexpressed (miRNA-24, miRNA-27b). MiRNA-136 was underexpressed in both OSCC vs. HCs and OSCC vs. OSCC-R. MiRNA-27b levels were significantly higher in OSCC patients compared to those found in HCs, patients with OSCC-R, and patients with oral lichen planus and served as a characteristic biomarker of OSCC. Receiver operating characteristic curve analyses showed that miRNA-27b could be a valuable biomarker for distinguishing OSCC patients from the other groups. Our novel findings established a reliable EC miRNA for salivary-based diagnostic and indicate that the salivary miRNA profiles are discriminatory in OSCC patients.

Aerosolised 5-azacytidine suppresses tumour growth and reprogrammes the epigenome in an orthotopic lung cancer model.

BACKGROUND: Epigenetic silencing by promoter methylation and chromatin remodelling affects hundreds of genes and is a causal event for lung cancer. Treatment of patients with low doses of the demethylating agent 5-azacytidine in combination with the histone deacetylase inhibitor entinostat has yielded clinical responses. The subcutaneous dosing route for consecutive days and reduced bioavailability of 5-azacytidine because of inactivation by cytidine deaminase may limit the expansion of epigenetic therapy into Phase III trials. To mitigate these barriers, an aerosol of 5-azacytidine was generated and characterised. METHODS: The effect of aerosol vs systemic delivery of 5-azacytidine on tumour burden and molecular response of engrafted lung tumours in the nude rat was compared. RESULTS: Pharmacokinetics revealed major improvement in the half-life of 5-azacytidine in lung tissue with aerosol delivery. Aerosolised 5-azacytidine significantly reduced lung tumour burden and induced global demethylation of the epigenome at one-third of the comparable effective systemic dose. High commonality for demethylation of genes was seen in tumours sampled throughout lung lobes and across treated animals receiving the aerosolised drug. CONCLUSION: Collectively, these findings show that aerosolised 5-azacytidine targets the lung, effectively reprogrammes the epigenome of tumours, and is a promising approach to combine with other drugs for treating lung cancer.

Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance.

JS-K is a nitric oxide (NO)-releasing prodrug of the O (2)-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH) via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion) spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

Evaluation of biodegradable paclitaxel-eluting nanofibre-covered metal stents for the treatment of benign cardia stricture in an experimental model.

BACKGROUND: Benign strictures at the cardia are troublesome for patients and often require repeated endoscopic treatments. Paclitaxel can reduce fibrosis. This study evaluated a biodegradable paclitaxel-eluting nanofibre-covered metal stent for the treatment of benign cardia stricture in vitro and in vivo. METHODS: Drug release was investigated in vitro at pH 7·4 and 4·0. Eighty dogs were divided randomly into four groups (each n = 20): controls (no stent), bare stent (retained for 1 week), and two drug-eluting stent (DES) groups with retention for either 1 week (DES-1w) or 4 weeks (DES-4w). Lower oesophageal sphincter pressure (LOSP) and 5-min barium height (5-mBH) were assessed before, immediately after stent deployment, at 1 week, and 1, 3 and 6 months later. Five dogs in each group were killed for histological examination at each follow-up point. RESULTS: Stent migration rates were similar (0 bare stent versus 2 DES; P = 0·548). The percentage and amount of paclitaxel released in vitro was higher at pH 4·0 than at pH 7·4. After 6 months, LOSP and 5-mBH were both improved in the DES-1w (P = 0·004 and P = 0·049) and DES-4w (both P < 0·001) groups compared with the bare-stent group, with better relief when the stent was retained for 4 weeks (P = 0·004 and P = 0·007). The DES was associated with a reduced peak inflammatory reaction and less scar formation compared with bare stents, especially when inserted for 4 weeks. CONCLUSION: The DES was more effective for the treatment of benign cardia stricture than bare stents in a canine model. Retention of the DES for 4 weeks led to a better clinical and pathological outcome than 1 week.

Biodegradable rapamycin-eluting nano-fiber membrane-covered metal stent placement to reduce fibroblast proliferation in experimental stricture in a canine model.

BACKGROUND AND STUDY AIMS: The aim of the current study was to assess whether placement of the biodegradable rapamycin-eluting nano-fiber membrane-covered metal stent is followed by less fibroblast proliferation and tissue hyperplasia compared with bare stents in experimental stricture in a dog model. METHODS: A total of 80 dog models of stricture were randomly divided into a control group (n = 20, no stent insertion), a bare stent group (BSG, n = 20, 1-week retention), and two drug-eluting stent sub-groups (DESG-1w, n = 20, 1-week retention; DESG-4w, n = 20, 4-week retention). Lower esophageal sphincter (LES) pressure, 5-minute barium height (5-mBH), and cardia diameter were assessed before, immediately after the procedure, and regularly thereafter for 6 months. Five dogs in each group were euthanized for histological examination at each follow-up assessment. RESULTS: Stent insertion was well tolerated, with similar migration rates (0 % in BSG vs. 7.5 % in DESGs; P = 0.5441). At 6 months, LES pressure and 5-mBH improved in DESG-1w (26.70 ± 5.02 mmHg and 6.50 ± 2.98 cm) and DESG-4w (20.16 ± 5.50 mmHg and 1.54 ± 0.98 cm) compared with BSG (39.94 ± 5.22 mmHg and 11.1 ± 5.46 cm) (P < 0.05), with DESG-4w being more stable than DESG-1w (P < 0.05). The cardia maintained greater patency in the DESGs (7.10 ± 3.09 mm in DESG-1w; 9.16 ± 3.77 mm in DESG-4w) than in the BSG (1.86 ± 2.45 mm; P < 0.05). Reduced peak inflammatory reactions and scarring occurred in DESGs compared with the BSG (P < 0.05), with a better outcome in DESG-4w than in DESG-1w (P < 0.05). CONCLUSIONS: In this experimental stricture model, rapamycin-eluting stents were more effective than bare stents for the reduction of fibroblast proliferation and tissue hyperplasia after stent placement. Furthermore, 4-week retention of the drug-eluting stent led to a better outcome than 1-week retention.

Depressed calcium-handling proteins due to endoplasmic reticulum stress and apoptosis in the diabetic heart are attenuated by argirein.

Diabetic cardiomyopathy (DC) is a unique disease frequently complicated to diabetes mellitus, manifesting endoplasmic reticulum (ER) stress and depressed calcium-handling proteins. We hypothesized that the abnormal FKBP12.6, SERCA2a, and CASQ2 are consequent to ER stress and apoptosis that are likely due to an entity of inflammation. These abnormalities may be attributed to reactive oxygen species genesis from activated NADPH oxidase which could respond to argirein (AR) through its anti-inflammatory activity. Sprague Dawley rats were randomly divided into six groups. Except the normal group, rats were injected with streptozotocin (STZ; 60 mg/kg, i.p.) once. During weeks 5 to 8 following STZ injection, rats were treated (in milligrams per kilogram per day, i.g.) with aminoguanidine (AMG, 100; an inducible nitric oxide synthase and AGEs inhibitor) or three doses of AR (50, 100, and 200). FKBP12.6, SERCA2a, and CASQ2 and ER stress chaperones Bip and PERK and apoptotic molecules were monitored in vivo and in vitro. Impaired cardiac performance and downregulated FKBP12.6, SERCA2a, and CASQ2 were significant in DC in vivo, and abnormal calcium-handling proteins were also found in high-glucose-incubated myocytes in vitro. ER stress manifested by upregulated Bip and PERK was predominant in association with DNA ladder and upregulated Bax and downregulated BCL-2 in vivo and in vitro. AR is effective to attenuate these abnormalities compared to AMG. Diabetic myocardium has inflammatory entity expressed as ER stress contributing to downregulated calcium-handling proteins. AR has potential in managing DC through attenuating depressed calcium-handling proteins, activated ER stress, and apoptosis in the myocardium.