Combsmagnusson3247

OBJECTIVE Patients with chronic hyperglycemia are at high risk of developing diabetic retinopathy. In this study, we investigated the functional role of long-noncoding RNA (lncRNA) X-inactive specific transcript (XIST) in anin vitro model of diabetic hyperglycemia in human retinal pigment epithelial ARPE-19 cells. METHOD ARPE-19 cells were cultured in normal glucose (NG) and high-glucose (HG) conditions to mimic hyperglycemia-associated cell apoptosis, migration and XIST expression. XIST was overexpressed in ARPE-19 cells to examine its functions in HG-induced cell apoptosis and migration. The downstream competing target of XIST, human mature microRNA-21-5p (hsa-miR-21-5p) was assessed by dual-luciferase assay and qRT-PCR. Hsa-miR-21-5p was upregulated in XIST-overexpressed ARPE-19 cells to further assess the functional correlation between XIST and hsa-miR-21-5p in hyperglycemia-associated cell apoptosis and migration. RESULTS HG insult increased apoptosis, reduced migration and downregulated XIST in ARPE-19 cells. XIST overexpression significantly protected HG insult in ARPE-19 cells, by reducing apoptosis and restoring migration capability. XIST directly bound and inhibited hsa-miR-21-5p expression in HG-insulted ARPE-19 cells. Furthermore, hsa-miR-21-5p upregulation reversed the protective effects of XIST in HG-insulted ARPE-19 cells. CONCLUSION XIST, likely through competitive binding of hsa-miR-21-5p, provides protection against hyperglycemia-associated injury in human retinal pigment epithelial cells. The antitumor effect of magnoflorine (Mag), an alkaloid isolated from Coptidis Rhizoma, in gastric cancer (GC) cells has not been reported. In the study, Mag suppressed the proliferation of GC cells, but showed no influence on normal gastric cells. Mechanistically, Mag induced autophagy in GC cells, as evidenced by the up-regulated expression of LC3B-II and increased autophagosome formation. Furthermore, we found that Mag-triggered autophagic cell death was regulated by reactive oxygen species (ROS)-induced suppression of serine/threonine-protein kinases (AKT) signaling. What's more, Mag treatment led to apoptosis in GC cells through enhancing cleaved Caspase-3 and PARP expressions. In addition, up-regulated expression of p27 and p21, as well as down-regulated expression of Cyclin-A and Cyclin-B1 was detected in Mag-treated GC cells, contributing to the S/G2 cell cycle arrest. Importantly, Mag incubation resulted in a significant increase in jun N-terminal kinase (JNK) phosphorylation but not p38 and ERK1/2, which was involved in the modulation of apoptosis and S/G2 phase arrest. Moreover, ROS production was highly induced by Mag treatment, and Mag-exhibited these functions was largely dependent on the generation of ROS in GC cells. Consistently, the GC cell xenograft mouse model confirmed the anti-tumor role of Mag in vivo. Collectively, these results indicated that Mag showed anti-GC effects, which could be a potential therapeutic target for GC treatment. Long non-coding RNAs (lncRNAs) are transcripts with sizes larger than 200 nucleotides and no/ small open reading frame that cannot produce functional proteins. The number of these transcripts surpasses the number of coding genes. LncRNAs regulate many aspects of cell functions such as proliferation, cell cycle transition and differentiation; so their dysregulation has pervasive effects on cell phenotype. Increasing numbers of these transcripts have been shown to participate in the pathogenesis of cancer. In the current review, we summarize recent findings regarding the role of lncRNAs in tumors originated from organs which have an endocrine function. We mostly focused on adrenal, pancreas and pituitary gland as prototypes of these organs. Moreover, we presented the obtained data of the role of lncRNAs in prostate, ovarian and testicular cancers. Recent data highly supports the role of lncRNAs in the pathogenesis of cancers originated from these organs. Moreover, certain genomic loci within lncRNAs have been shown to be associated with risk of these cancers. Diagnostic and prognostic role of some lncRNAs in these cancers have been evaluated recently. Taken together, lncRNAs are putative biomarkers for cancers originated from organs which have an endocrine function. Cervical cancer is still a leading cause of tumor death in women across the world. Small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene encodes the components of the core spliceosomal machinery, and regulates the development of several types of cancers. However, its function in cervical cancer progression remains unclear. In the study, we found that SNRPB was highly expressed in human cervical cancer tissues and in cervical cancer cell lines. Meanwhile, SNRPB knockdown using shRNA in cervical cancer cells markedly reduced the cell proliferation, migration and invasion. Furthermore, the increased percentage of cells in G2/M phase and apoptotic cell death was detected in cervical cancer cells with SNRPB knockdown, suggesting that SNRPB might contribute to cervical cancer growth. Moreover, we found that SNRPB could directly interact with p53, and the interaction showed an essential role in modulating cervical cancer cell proliferation, migration, invasion and apoptosis. In xenograft model, the knockdown of SNRPB exerted effectively anti-cervical cancer ability characterized by the reduced tumor volume and weight, and a remarkable reduction in KI-67 expression. Improved expression of p53 validated the in vitro findings. Therefore, SNRPB might be a potent therapeutic target in cervical cancer through interacting with p53. Background/Aims Aspiration therapy (AT) involves endoscopic placement of a gastrostomy tube with an external device that allows patients to drain 30% of ingested calories after meals. Its efficacy for inducing weight loss has been shown. This study aimed to assess the effect of AT on obesity-related comorbidities. Methods A meta-analysis of studies that assessed AT outcomes was conducted through December 2018. Primary outcomes were changes in comorbidities at 1 year following AT. Secondary outcomes were the amount of weight loss at up to 4 years and pooled serious adverse events (SAEs). Results Five studies with 590 patients were included. At 1 year, there were improvements in metabolic conditions mean difference (MD) in systolic blood pressure -7.8 (-10.7 - -4.9) mm Hg; MD in diastolic blood pressure -5.1 (-7.0 - 3.2) mm Hg; MD in triglycerides -15.8 (-24.0 - -7.6) mg/dL; MD in high-density lipoprotein 3.6 (0.7-6.6) mg/dL; MD in hemoglobin A1c (HbA1c) -1.3 (-1.8 - -0.8) %; MD in aspartate transaminase -2.7 (-4.1 - -1.3) U/L; MD in alanine transaminase -7.5 (-9.8 - -5.2) U/L. At 1 (n=218), 2 (n=125), 3 (n=46), and 4 (n=27) years, the patients experienced 17.8%, 18.3%, 19.1%, and 18.6% total weight loss (TWL), corresponding to 46.3%, 46.2%, 48.0%, and 48.7% excess weight loss (EWL) (p less then 0.0001 for all). Subgroup analysis of 2 randomized controlled trials (n=225) showed that AT patients lost more weight than did controls by 11.6 (6.5-16.7) %TWL and 25.6 (16.0-35.3) %EWL and experienced greater improvement in HbA1c and alanine transaminase by 1.3 (0.8-1.8) % and 9.0 (3.9-14.0) U/L. The pooled SAE rate was 4.1%. Conclusions Obesity-related comorbidities significantly improved at 1 year following AT. Additionally, a subgroup of patients who continued to use AT appeared to experience significant weight loss that persisted up to at least 4 years.BACKGROUND The advantages of simultaneous bilateral total knee arthroplasty (sim-BTKA) remain controversial. This study investigated the effects of two-surgeon sim-BTKA compared to separate admission staged BTKA regarding intraoperative and post-operative outcomes and health service costs. METHODS Patients underwent sim-BTKA or staged BTKA between 1 November 2008 and 30 June 2016. Data were extracted from a joint replacement registry and medical records. Median regression and chi-squared tests were used for between-group comparisons. RESULTS Median hospital total length of stay was 5 days less for sim-BTKA (n = 122) than staged BTKA group (n = 46) (7 versus 12; 95% confidence interval (CI) 3.9, 6.1), and 9 days less for inpatient rehabilitation (17 versus 26; 95% CI 3.7, 14.3). However, 80% of sim-BTKA patients went to inpatient rehabilitation (versus 27% following staged BTKA), so median total length of stay was 9 days less for staged BTKA (13 versus 22; 95% CI -12.8, -5.2). Total anaesthesia time was 135 min less for sim-BTKA (P  less then  0.001), while staged BTKA required less blood transfusions (P = 0.001). Complication rates were similar, except for superficial infections which were observed twice as often after staged BTKA (30% versus 15%, P = 0.048). Twelve months following sim-BTKA and the first staged total knee arthroplasty, sim-BTKA had better WOMAC pain, stiffness and function scores (P ≤ 0.05). Average inpatient costs (hospital and rehabilitation) were $6388 less for sim-BTKA. CONCLUSION Sim-BTKA appears to be a comparatively safe alternative to staged BTKA. Sim-BTKA may be superior to staged BTKA due to faster improvements in pain and function and lower healthcare costs. How these results generalize to other health services requires further investigation. © 2020 Royal Australasian College of Surgeons.OBJECTIVE Infantile spasm syndrome (ISS) is an epileptic encephalopathy without established treatment after the failure to standard of care based on steroids and vigabatrin. Converging lines of evidence indicating a role of NR2B subunits of the N-methyl-D-aspartate (NMDA) receptor on the onset of spams in ISS patients, prompted us to test radiprodil, a negative allosteric NR2B modulator in preclinical seizure models and in infants with ISS. METHODS Radiprodil has been tested in three models, including pentylenetetrazole-induced seizures in rats across different postnatal (PN) ages. Three infants with ISS have been included in a phase 1b escalating repeated dose study. RESULTS Radiprodil showed the largest protective seizure effects in juvenile rats (maximum at PN12, corresponding to late infancy in humans). Three infants resistant to a combination of vigabatrin and prednisolone received individually titrated doses of radiprodil for up to 34 days. Radiprodil was safe and well tolerated in all three infants, and showed the expected pharmacokinetic profile. One infant became spasm-free and two showed clinical improvement without reaching spasm-freedom. After radiprodil withdrawal, the one infant continued to be spasm-free, while the two others experienced seizure worsening requiring the use of the ketogenic diet and other antiepileptic drugs. INTERPRETATION Radiprodil showed prominent anti-seizure effect in juvenile animals, consistent with the prevalent expression of NR2B subunit of the NMDA receptor at this age in both rodents and humans. The clinical testing, although preliminary, showed that radiprodil is associated with a good safety and pharmacokinetic profile, and with the potential to control epileptic spasms. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.