Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II-III Colorectal Cancer.

BACKGROUND: The Naples prognostic score (NPS) is a scoring system that reflects a patient's systemic inflammatory and nutritional status. This study aimed to evaluate whether postoperative NPS is effective in assessing the prognosis of stage II-III colorectal cancer (CRC) patients compared with preoperative NPS. METHODS: Between 2005 and 2012, a total of 164 patients diagnosed with stage II-III CRC, who underwent curative resection followed by adjuvant chemotherapy, were divided into two groups: Group 0-1 (NPS = 0-2) and Group 2 (NPS = 3 or 4). Preoperative NPS was calculated based on the results before surgeries, and postoperative NPS was assessed using the results obtained before adjuvant chemotherapy. RESULTS: The overall survival of Group 0-1 was higher than that of Group 2 in both pre- and postoperative NPS assessments. According to the ROC curve analysis, the Area Under the Curve (AUC) ratio for postoperative NPS was 0.64, compared with 0.57 for preoperative NPS, 0.52 for the preoperative neutrophil-lymphocyte ratio (p = 0.032), and 0.51 for the preoperative platelet-lymphocyte ratio (p = 0.027). CONCLUSIONS: Postoperative NPS is effective in predicting the prognosis of stage II-III CRC patients who underwent curative resection followed by adjuvant chemotherapy. The use of NPS could be beneficial in evaluating the prognosis of CRC patients after surgeries.

hnRNP Q and hnRNP A1 Regulate the Translation of Cofilin in Response to Transient Oxygen-Glucose Deprivation in Hippocampal Neurons.

Protein aggregates of cofilin and actin have been found in neurons under oxygen-glucose deprivation. However, the regulatory mechanism behind the expression of Cfl1 during oxygen-glucose deprivation remains unclear. Here, we found that heterogeneous nuclear ribonucleoproteins (hnRNP) Q and hnRNP A1 regulate the translation of Cfl1 mRNA, and formation of cofilin-actin aggregates. The interaction between hnRNP A1 and Cfl1 mRNA was interrupted by hnRNP Q under normal conditions, while the changes in the expression and localization of hnRNP Q and hnRNP A1 increased such interaction, as did the translation of Cfl1 mRNA under oxygen-glucose deprived conditions. These findings reveal a new translational regulatory mechanism of Cfl1 mRNA in hippocampal neurons under oxygen-glucose deprivation.

The neuroprotective effects of pregabalin after cerebral ischemia by occlusion of the middle cerebral artery in rats.

Activation of presynaptic voltage-gated calcium channels and glutamate release serves a central role in neuronal necrosis after cerebral ischemia. Pregabalin binds to the α2-δ subunit of voltage-gated calcium channels and results in reduced glutamate release. The aim of the current study was to evaluate the effect of pregabalin on cerebral outcome following cerebral ischemia using an established rat model. Male Sprague-Dawley rats were randomized to receive oral administration of 5 mg/kg pregabalin for 1 day (PD1 group) or 5 days (PD5 group), or an equal amount of normal saline for 1 day (SD1 group) or 5 days (SD5 group) after 1 day of middle cerebral artery occlusion (MCAO) and reperfusion. Behavioral tests were assessed at postoperative days 1 and 7. Cerebral infarct volume was measured using a brain MRI scan on days 1 and 7 following surgery. Using immunohistochemistry to detect brain-derived neurotrophic factor (BDNF), histologic examinations of perilesional cortex and ipsilateral hippocampus were performed at postoperative day 7. BDNF-positive immunostaining was more abundant in the perilesional cortex of mice of the PD1 group compared with mice of the SD1 group (P=0.001). In the ipsilateral hippocampus, greater BDNF-positive staining was present in the PD5 group compared with the SD5 group (P=0.04). No statistically significant differences were indicated for behavioral tests or cerebral infarct volume between the PD1 and SD1 groups or the PD5 and SD5 groups. In conclusion, treatment with pregabalin beneficially impacts BDNF expression and histologic cerebral outcome in rats after cerebral ischemia.

Value of serum procalcitonin as an early predictor of antibiotic treatment response in inpatients with pelvic inflammatory disease (VALID).

OBJECTIVE: This study aimed to investigate the value of serum procalcitonin as an early predictor of antibiotic treatment response in the inpatient management of pelvic inflammatory disease (PID). MATERIALS AND METHODS: A prospective observational study was carried out at a university hospital. Patients admitted for pelvic inflammatory disease were classified into 2 groups: responders and non-responders. The primary outcome measure was the serum level of procalcitonin at the time of admission. The secondary outcome measures were other serum inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. RESULTS: Baseline characteristics were similar between the groups. Serum level of procalcitonin at the time of admission did not differ between the groups (P = 0.564). However, the non-responders had more elevated CRP and ESR compared to the responders (P = 0.045 and P = 0.030, respectively). CRP showed the highest accuracy of 72.1% (95% confidence interval [CI], 59.2 to 82.9) in predicting antibiotics response, while procalcitonin showed the lowest accuracy of 49.1% (95% CI, 35.1 to 63.2). CONCLUSION: Compared with standard inflammatory markers such as CRP or ESR, procalcitonin had limited diagnostic value in predicting antibiotics response in patients admitted for PID. Therefore, procalcitonin measurement cannot be recommended as a laboratory test for patients with PID and the value of its routine use remains inconclusive.

Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation.

Macrophage migration inhibitory factor (MIF) is a chemokine that plays an essential role in immune system function. Previous studies suggested that MIF protects neurons in ischemic conditions. However, few studies are reported on the role of MIF in neurological recovery after ischemic stroke. The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF. Human neuroblastoma cells were incubated in Dulbecco's modified Eagle's medium under oxygen-glucose deprivation (OGD) for 4 hours and then returned to normal aerobic environment for reperfusion (OGD/R). 30 ng/mL MIF recombinant (30 ng/mL) or ISO-1 (MIF antagonist; 50 µM) was administered to human neuroblastoma cells. Then cell cultures were assigned to one of four groups: control, OGD/R, OGD/R with MIF, OGD/R with ISO-1. Cell viability was analyzed using WST-1 assay. Expression levels of brain-derived neurotrophic factor (BDNF), microtubule-associated protein 2 (MAP2), Caspase-3, Bcl2, and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity. WST-1 assay results revealed that compared to the OGD/R group, cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group. Western blot assay and immunocytochemistry results revealed that expression levels of BDNF, Bcl2, and MAP2 were significantly higher, and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group. Expression levels of BDNF, Bcl2, and MAP2 were significantly lower, and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group. MIF administration promoted neuronal cell survival and induced high expression levels of BDNF, MAP2, and Bcl2 (anti-apoptosis) and low expression levels of Caspase-3 and Bax (pro-apoptosis) in an OGD/R model. These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.

The Rate of Mesh Erosion after Modified Transobturator Tape (Canal Transobturator Tape) Surgery: Analysis of 5 years' Outcome and Influencing Factors.

PURPOSE: To evaluate the long-term cure and complication rates of the canal transobturator tape (TOT) procedure for stress urinary incontinence (SUI) in females and assess how to reduce mesh erosion in TOT surgery. MATERIALS AND METHODS: The canal TOT procedure was developed in 2009 and was effective in mitigating the complications of the original TOT procedure in the short-term follow-up. This study was designed for a long-term follow-up. Between October 2006 and December 2010, 232 consecutive women with stress and mixed urinary incontinence underwent the canal TOT procedure. All patients were followed up by urological examination and self-assessment questionnaires. We performed urodynamic studies in patients with pure SUI symptoms and pelvic examination for all patients 5 years post-surgery. RESULTS: A minimum 5 years follow-up data were available for 144 patients. Complications were evaluated according to the Clavien-Dindo classification. Vaginal mesh erosion was reported in 2 patients (1.4%), and the mesh was surgically removed. No bladder or urethral mesh erosion were observed. The subjective and objective cure rates at 5 years were 77.8 and 94.5% respectively. CONCLUSIONS: Canal TOT procedure is an effective minimally invasive procedure with satisfactory results for female SUI in the long term. Compared to the rate of mesh erosion after the original TOT procedure, this technique might be useful in preventing mesh erosion because the mesh is always anatomically well positioned.

Activation of sphingosine kinase 2 by endoplasmic reticulum stress ameliorates hepatic steatosis and insulin resistance in mice.

UNLABELLED: The endoplasmic reticulum (ER) is the principal organelle in the cell for protein folding and trafficking, lipid synthesis, and cellular calcium homeostasis. Perturbation of ER function results in activation of the unfolded protein response (UPR) and is implicated in abnormal lipid biosynthesis and development of insulin resistance. In this study, we investigated whether transcription of sphingosine kinase (Sphk)2 is regulated by ER stress-mediated UPR pathways. Sphk2, a major isotype of sphingosine kinase in the liver, was transcriptionally up-regulated by tunicamycin and lipopolysaccharides. Transcriptional regulation of Sphk2 was mediated by activation of activating transcription factor (ATF)4 as demonstrated by promoter assays, immunoblotting, and small interfering RNA analyses. In primary hepatocytes, adenoviral Sphk2 expression elevated cellular sphingosine 1 phosphate (S1P) and activated protein kinase B phosphorylation, with no alteration of insulin receptor substrate phosphorylation. Hepatic overexpression of Sphk2 in mice fed a high-fat diet (HFD) led to elevated S1P and reduced ceramide, sphingomyelin, and glucosylceramide in plasma and liver. Hepatic accumulation of lipid droplets by HFD feeding was reduced by Sphk2-mediated up-regulation of fatty acid (FA) oxidizing genes and increased FA oxidation in liver. In addition, glucose intolerance and insulin resistance were ameliorated by improved hepatic insulin signaling through Sphk2 up-regulation. CONCLUSION: Sphk2 is transcriptionally up-regulated by acute ER stress through activation of ATF4 and improves perturbed hepatic glucose and FA metabolism.

Endotoxin activates de novo sphingolipid biosynthesis via nuclear factor kappa B-mediated upregulation of Sptlc2.

Sphingolipids are membrane components and are involved in cell proliferation, apoptosis and metabolic regulation. In this study we investigated whether de novo sphingolipid biosynthesis in macrophages is regulated by inflammatory stimuli. Lipopolysaccharide (LPS) treatment upregulated Sptlc2, a subunit of serine palmitoyltransferase (SPT), mRNA and protein in Raw264.7 and mouse peritoneal macrophages, but Sptlc1, another subunit of SPT, was not altered. SPT activation by LPS elevated cellular levels of ceramides and sphingomyelin (SM). Pharmacological inhibition of nuclear factor kappa B (NFκB) prevented LPS-induced upregulation of Sptlc2 while transfection of p65 subunit of NFκB upregulated Sptlc2 and increased cellular ceramide levels. In contrast, MAP kinases were not involved in regulation of sphingolipid biosynthesis. Analysis of Sptlc2 promoter and chromatin immunoprecipitation (ChIP) assay showed that NFκB binding sites are located in Sptlc2 promoter region. Our results demonstrate that inflammatory stimuli activate de novo sphingolipid biosynthesis via NFκB and may play a critical role in lipid metabolism in macrophages.