Inhibitory Effects of Resveratrol on PDGF-BB-Induced Retinal Pigment Epithelial Cell Migration via PDGFRβ, PI3K/Akt and MAPK Pathways

Purpose: In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue. Methods: The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay. Results: Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor β (PDGFRβ) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration. Conclusions: These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRβ, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin

Psoas Abscess Caused by Non-Typhoid Salmonella in a Patient with Severe Aplastic Anemia

The clinical spectrum of infections caused by non-typhoid Salmonella spp. includes gastroenteritis, enteric fever, bacteremia, and extraintestinal localized complications, especially in immunocompromised hosts. Here we report a patient with severe aplastic anemia developing left iliopsoas abscess caused by non-typhoid Salmonella (NTS), which was successfully treated by prolonged antibiotic treatment and repeated debridement. Our data indicate that aplastic anemia is a risk factor for infection caused by NTS

Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery

Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome. Methods A multicenter prospective observational study based on the NSARF ( National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 +/- 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006. Results The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality. Conclusions The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification

Acute kidney injury in patients with COVID-19 compared to those with influenza: a systematic review and meta-analysis

BackgroundCOVID-19 and influenza can both lead to acute kidney injury (AKI) as a common complication. However, no meta-analysis has been conducted to directly compare the incidence of AKI between hospitalized patients with COVID-19 and influenza. The objective of our study aims to investigate the incidence and outcomes of AKI among hospitalized patients between these two groups.Materials and methodsA systematic search of PubMed, Embase, and Cochrane databases was conducted from December 2019 to August 2023 to identify studies examining AKI and clinical outcomes among hospitalized patients with COVID-19 and influenza. The primary outcome of interest was the incidence of AKI, while secondary outcomes included in-hospital mortality, recovery from AKI, hospital and ICU stay duration. The quality of evidence was evaluated using Cochrane and GRADE methods.ResultsTwelve retrospective cohort studies, involving 17,618 hospitalized patients with COVID-19 and influenza, were analyzed. COVID-19 patients showed higher AKI incidence (29.37% vs. 20.98%, OR: 1.67, 95% CI 1.56–1.80, p &lt; 0.01, I2 = 92.42%), and in-hospital mortality (30.95% vs. 5.51%, OR: 8.16, 95% CI 6.17–10.80, p &lt; 0.01, I2 = 84.92%) compared to influenza patients with AKI. Recovery from AKI was lower in COVID-19 patients (57.02% vs., 80.23%, OR: 0.33, 95% CI 0.27–0.40, p &lt; 0.01, I2 = 85.17%). COVID-19 patients also had a longer hospital stay (SMD: 0.69, 95% CI 0.65–0.72, p &lt; 0.01, I2 = 98.94%) and longer ICU stay (SMD: 0.61, 95% CI 0.50–0.73, p &lt; 0.01, I2 = 94.80%) than influenza patients. In our study, evidence quality was high (NOS score 7–9), with low certainty for AKI incidence and moderate certainty for recovery form AKI by GRADE assessment.ConclusionCOVID-19 patients had higher risk of developing AKI, experiencing in-hospital mortality, and enduring prolonged hospital/ICU stays in comparison to influenza patients. Additionally, the likelihood of AKI recovery was lower among COVID-19 patients

Ile/Ile homozygosity at codon 655 of HER2 in schwannoma

[[abstract]]Purpose: This study aimed to determine the genetic role of HER2, one of the epidermal growth factor receptor (EGFR) family, in schwannoma. The latter is a neogrowth of myelin-producing Schwann cells in peripheral nerves, inducible by N-nitrosoethylurea in animals with mutation in the neu gene (homologous gene of human HER2 protein).Methods: In this study we obtained genomic DNA samples from tissue blocks of schwannoma, initially by xylene treatment and alcohol extraction, followed by use of the DNA extraction kit. Evaluation of this genetic polymorphism in our subjects was conducted by direct nucleotide sequencing or restriction enzyme analyses after PCR work.Results: There were thirty extracted DNA samples from tissue blocks of schwannoma, and all were Ile/Ile homozygotes after genotype analyses. Two individuals received the leukocyte DNA extraction after peripheral blood sampling, both showing Ile/Ile homozygosity. This study gave the impression of an association of the HER2 polymorphism at codon 655 with tumorigenesis of schwannoma. Although the majority of the Taiwanese showed Ile/Ile homozygosity (about 83%), the present study revealed a 100%carriage rate among the tissue blocks from our subjects with schwannoma.Conclusion: Ile/Ile homozygosity at codon 655 of HER2 in schwannoma may imply some role in tumorigenesis of Ile655Val allele of HER2 in this nerve tumor.[[journaltype]]國內[[booktype]]電子版[[countrycodes]]TW

Ultrasound Imaging for the Diagnosis and Evaluation of Sarcopenia: An Umbrella Review

There is an increasing number of reviews investigating the value of ultrasound (US) in the assessment of aging-related muscle loss. The present umbrella review aimed to systematically investigate the evidence of US imaging in the diagnosis and evaluation of sarcopenia. PubMed, Medline, Embase and Web of Science were searched from their inceptions to 31 October 2021. Systematic reviews and reviews using a systematic strategy for literature search were enrolled. The extracted data were narrated at the level of systematic reviews and meta-analyses. This umbrella review included four articles pertaining to 125 original studies and yielded several important findings. First, US is a reliable and valid imaging tool for the assessment of skeletal muscle mass. Second, among all the US parameters in B-mode, muscle thickness is the most commonly used one, which has good correlation with other standard measurements. Third, although sonoelastography and contrast-enhanced US are promising imaging modalities, their clinical utility is still limited at the current stage. Finally, a future systematic review is warranted to analyze how different ultrasonographic diagnostic criteria influence the prevalence of sarcopenia as well as its adverse health outcomes

Transwell migration assay showed that PDGF-BB-induced ARPE19 cell migration was inhibited by resveratrol.

<p>Transwell inserts were coated with fibronectin (0.3 mg). ARPE19 cells (5×10⁴ in 200 µl) were seeded in the upper chamber in the absence or presence of resveratrol. The inserts were assembled in the lower chamber, which was filled with 600 µl serum-free medium without PDGF-BB (A) and containing PDGF-BB (20 ng/ml) (B), and preincubated with various concentrations of resveratrol for 30 mininutes at 37°C. After incubating for 5 hours at 37°C, fixation was performed. ARPE19 cells that migrated to the underside of filter membrane were photographed (A, B) and counted by phase contrast light microscope under high power field (magnification, 100×), (C). All experiments were conducted in duplicates and similar results were repeated four times. The results are expressed as percentage of control and represent mean ± standard errors (SE) of the eight experiments. *p<0.05 significantly differs from PDGF-BB-stimulated cells (the fourth bar).</p

Viability and cell adhesion of ARPE19 cells was not influenced by resveratrol.

<p>The cells were treated with different concentrations of resveratrol for 24 hours after being starved for 24 hours. Cell viability was determined by MTT assay (A). BCECF-labeled cells were treated with DMSO or resveratrol for 30 minutes. They were then seeded and allowed to adhere on plates with precoated fibronectin (fn) (15 µg/ml) at 37°C for 1 hour. Fluorescence was measured using excitation and emission wavelength of 485 and 535 nm, respectively (B). The results are expressed as percentage of control and represent the mean ± standard errors (SE) of four independent experiments.</p

PDGF-BB-induced ERK and P38 phosphorylations were inhibited by resveratrol in a time- and concentration-dependant manner.

<p>ARPE19 cells were treated with the indicated lengths of time of PDGF-BB (20 ng/ml) and preincubated with or without resveratrol (10 µM) at 37°C (A). After being further preincubated for the indicated concentrations of resveratrol and incubated with or without PDGF-BB (20 ng/ml) at 37°C for 30 minutes, the cells were collected and their lysates were analyzed by Western blot analysis (B). The changes in phosphorylated ERK, JNK and p38 expression were evaluated. The quantitative data of western blot are shown below the panels which are expressed as percentage of control and represent mean ± standard errors (SE) of the four independent experiments. *p<0.05 significantly differs from same indicated time of cells stimulated PDGF-BB only (A) and *p<0.05 significantly differs from PDGF-BB-stimulated cells (the fifth bar) (B).</p

PDGF-BB-induced cell migrations were inhibited by resveratrol and by suppression of PDGFR, PI3K/Akt and MAPK signaling.

<p>The plates with confluent monolayer of ARPE cells were pretreated with mitomycin-C (5 µg/ml) for 1 hour, then wounded with a linear scratching by a sterile 20- µl pipette tip. The cells were immediately washed and were incubated with PDGF-BB (20 ng/ml) only, PDGF-BB in combination with resveratrol (10 µM), AG1295 (10 µM), LY294002 (10 µM), U0126 (10 µM), SP600125 (3 µM) and SB203580 (3 µM) respectively. The wound closure was monitored for 16 h followed by photography under phase-contrast microscope (x100) (A). The quantitative data of the number of migrated cell in the wound area are expressed as percentage of control and represent mean ± standard errors (SE) of the four independent experiments. *p<0.05 significantly differs from PDGF-BB-stimulated cells (the second bar) (B).</p