• Ulrich Kenney opublikował 1 rok, 8 miesięcy temu

    nts undergoing cardiac surgery with CPB. TRIAL REGISTRATION EudraCT (clinicaltrialsregister.eu) 2015-002556-27 Registered 11 Nov 2016 and ClinicalTrials.gov NCT02560519. Registered 25 Sept 2015.BACKGROUND FK506-binding protein 9 (FKBP9) is amplified in high-grade gliomas (HGGs). However, the roles and mechanism(s) of FKBP9 in glioma are unknown. METHODS The expression of FKBP9 in clinical glioma tissues was detected by immunohistochemistry (IHC). The correlation between FKBP9 expression levels and the clinical prognosis of glioma patients was examined by bioinformatic analysis. Glioblastoma (GBM) cell lines stably depleted of FKBP9 were established using lentiviruses expressing shRNAs against FKBP9. The effects of FKBP9 on GBM cells were determined by cell-based analyses, including anchorage-independent growth, spheroid formation, transwell invasion assay, confocal microscopy, immunoblot (IB) and coimmunoprecipitation assays. In vivo tumor growth was determined in both chick chorioallantoic membrane (CAM) and mouse xenograft models. RESULTS High FKBP9 expression correlated with poor prognosis in glioma patients. Knockdown of FKBP9 markedly suppressed the malignant phenotype of GBM cells in vitro and inhibited tumor growth in vivo. Mechanistically, FKBP9 expression induced the activation of p38MAPK signaling via ASK1. Furthermore, ASK1-p38 signaling contributed to the FKBP9-mediated effects on GBM cell clonogenic growth. In addition, depletion of FKBP9 activated the IRE1α-XBP1 pathway, which played a role in the FKBP9-mediated oncogenic effects. Importantly, FKBP9 expression conferred GBM cell resistance to endoplasmic reticulum (ER) stress inducers that caused FKBP9 ubiquitination and degradation. CONCLUSIONS Our findings suggest an oncogenic role for FKBP9 in GBM and reveal FKBP9 as a novel mediator in the IRE1α-XBP1 pathway.BACKGROUND Three-dimensional Surface Imaging (3DSI) is a well-established method to objectively monitor morphological changes in the female breast in the field of plastic surgery. In contrast, in radiation oncology we are still missing effective tools, which can objectively and reproducibly assess and document adverse events in breast cancer radiotherapy within the framework of clinical studies. The aim of the present study was to apply structured-light technology as a non-invasive and objective approach for the documentation of cosmetic outcome and early effects of breast radiotherapy as a proof of principle. METHODS Weekly 3DSI images of patients receiving either conventionally fractionated radiation treatment (CF-RT) or hypofractionated radiation treatment (HF-RT) were acquired during the radiotherapy treatment and clinical follow-up. The portable Artec Eva scanner (Artec 3D Inc., Luxembourg) recorded 3D surface images for the analysis of breast volumes and changes in skin appearance. Statistical analysis ing 3D structured-light technology as a non-invasive and objective approach for the documentation of patients receiving breast radiotherapy. 3DSI offers potential as a non-invasive tool to objectively and precisely monitor the female breast in a radiooncological setting, allowing clinicians to objectively distinguish outcomes of different therapy modalities.BACKGROUND Circular RNA (circRNA) has been proven to play a significant role in multiple types of cancer. However, the expression and role of circRNAs in epithelial ovarian cancer (EOC) remains elusive. METHODS CircRNA and mRNA expression profiles of EOC were screened with sequencing analysis. Gene silencing and over-expression were used to study circRNA function. Cell proliferation and Matrigel invasion assays were used to detect cell proliferation and invasion, respectively. The expression of circRNAs, mRNAs and miRNAs was detected using qPCR. The location of circRNAs was detected using FISH. The expression of proteins was detected using western blot and immunohistochemistry. RESULTS CircMUC16 had increased expression in EOC tissues as compared to healthy ovarian tissues. The expression of circMUC16 was linked to the progression in stage and grade of EOC. Hence, silencing circMUC16 suppressed autophagy flux of SKOV3 cells. In contrast, ectopic expression of circMUC16 promoted autophagy flux of A2780 cells. CircMUC16-mediated autophagy exacerbated EOC invasion and metastasis. Mechanistically, circMUC16 could directly bind to miR-199a-5p and relieve suppression of target Beclin1 and RUNX1. In turn, RUNX1 elevated the expression of circMUC16 via promotion of its transcription. CircMUC16 could directly bind to ATG13 and promote its expression. CONCLUSION This study demonstrated that circMUC16 regulated Beclin1 and RUNX1 by sponging miR-199a-5p. The data suggested that circMUC16 could be a potential target for EOC diagnosis and therapy.BACKGROUND The 2012 Global Lung Function Initiative (GLI2012) provide multi-ethnic spirometric reference equations (SRE) for the 3-95 year-old age range, but Sub-Saharan African populations are not represented. This study aimed to evaluate the fit of the African-American GLI2012 SRE to a population of healthy urban and peri-urban Zimbabwean school-going children (7-13 years). METHODS Spirometry and anthropometry were performed on black-Zimbabwean children recruited from three primary schools in urban and peri-urban Harare, with informed consent and assent. Individuals with a history or current symptoms of respiratory disease or with a body mass index-z score (BMI)  less then  - 2 were excluded. Spirometry z-scores were generated from African-American GLI2012 SRE, which adjust for age, sex, ethnicity and height, after considering all GLI2012 modules. Anthropometry z-scores were generated using the British (1990) reference equations which adjust for age and sex. The African-American GLI2012 z-score distributione African-American GLI2012 SRE provided a better fit for Zimbabwean paediatric spirometry data than Polgar equations. CONCLUSION The use of African-American GLI2012 SRE in this population could help in the interpretation of pulmonary function tests.BACKGROUND Giardia duodenalis causes giardiasis in humans, particularly in developing countries. Despite the availability of treatments, resistance to some of the commercial anti-Giardia drugs has been reported in addition to their harmful side effects. Therefore, novel treatments for giardiasis are required. In this study, we aimed to assess the in vitro activity of crude extracts of Ageratum conyzoides against G. duodenalis trophozoites. METHODS Plants were classified into three groups based on their flower colors white (W), purple (P), and white-purple (W-P). Plants were separately cut into leaf (L) and flower (F) parts. Changes in internal organelle morphology of trophozoites following exposure to crude extracts were assessed using transmission electron microscopy (TEM). In subsequent experiments, efficacy of the most active essential oils from crude extracts [half maximal inhibitory concentrations (IC50) ≤ 100 μg/mL] against G. duodenalis trophozoites was tested. In vitro anti-Giardia assays using essential oils were performed in the same way as those performed using crude extracts. RESULTS LW-P and FP extracts showed high activity (IC50 ≤ 100 μg/mL) against G. duodenalis trophozoites, with IC50 ± SD values of 45.67 ± 0.51 and 96.00 ± 0.46 μg/mL, respectively. In subsequent experiments, IC50 ± SD values of LW-P and FP essential oils were 35.00 ± 0.50 and 89.33 ± 0.41 μg/mL, respectively. TEM revealed the degeneration of flagella and ventral discs of G. duodenalis trophozoites following exposure to crude extracts. CONCLUSION Crude LW-P and FP extracts of A. conyzoides showed the highest activity against G. duodenalis. Exposure to crude extract induced changes in the flagella and ventral discs of G. duodenalis trophozoites, which play important roles in attachment to the surface of mucosal cells. Our results suggest that the tested extracts warrant further research in terms of their efficacy and safety as giardiasis treatment.BACKGROUND The aim of this study was to determine the radiographic, second-look, and functional outcomes after arthroscopic side-to-side repair for complete radial posterior lateral meniscus root tears (PLMRTs). METHODS Patients who underwent arthroscopic side-to-side repair for complete radial PLMRTs were identified. Clinical assessment consisted of symptoms (locking, catching, giving way and effusion), examinations of joint-line tenderness and McMurray test, and subjective scores of International Knee Documentation Committee (IKDC), Lysholm, and Tegner. In addition, postoperative MRI scan and second-look arthroscopy were performed to assess the healing status of the repaired meniscus. RESULTS Twenty-nine patients met the inclusion criteria. The mean age was 25.41 years. The mean follow-up period was 26.68 months. During the follow-up, none of the patients had symptoms of meniscal retear, lateral joint-line tenderness or a positive McMurray test. The postoperative subjective scores of IKDC, Lysholm, and Tegner improved significantly compared to the preoperative values (P = 0.01). Postoperative MRI scan showed that 28/29 (96.6%) patients achieved meniscus healing. Twenty-two patients underwent second-look arthroscopy, among whom 19 (86.4%) patients showed complete meniscus healing and 3 (13.6%) patients showed partial healing. CONCLUSION Arthroscopic side-to-side repair was a valuable surgical repair technique for complete radial PLMRTs, which leaded to significant improvements in both objective and subjective functional outcomes with a high rate of meniscus healing. LEVEL OF EVIDENCE Level IV, case series.BACKGROUND We investigated the incidence and location of heterotopic ossification (HO) following hip arthroscopy. METHODS This retrospective study enrolled 327 patients who underwent hip arthroscopy from January 2010 to December 2015. From this cohort, we extracted an HO group with simple radiographs or three-dimensional computed tomography (3D CT). Findings consistent with HO were classified according to the Brooker classification aided with 3D CT for the location of HO. The indication for revision arthroscopic excision of HO was painful, functional impairment of the hip. Patient clinical outcomes were assessed pre- and postoperatively, with modified Harris Hip Scores (mHHS), a visual analogue scale (VAS) for pain, and the Hip Outcome Score-Activity of Daily Living (HOS-ADL) and Sport Specific Subscales (HOS-SSS). RESULTS In all, 14 (4.28%) of the 327 patients had confirmed HO radiographically. The mean follow-up was 39 months. In 13 patients, HO formed in the central area of the arthroscopic portals or capsulotomy. Ten patients had Brooker Grade 1 and four had Grade 2. At the last follow-up, 12 asymptomatic patients had significant (P  less then  0.001) improvements in all clinical outcome scores (mHHS, pain VAS, HOS-ADL, and HOS-SSS). Two patients developed symptoms sufficient to require revision hip arthroscopy for HO excision. After revision hip arthroscopy, both symptomatic patients had improved significantly in all clinical outcomes at the final follow-up. CONCLUSIONS HO is a minor complication of hip arthroscopy, but sometimes induces severe pain and functional impairment. Usually, HO forms in the arthroscopic portal or capsulotomy area.

Szperamy.pl
Logo
Enable registration in settings - general
Compare items
  • Total (0)
Compare
0