Hyperbaric oxygen therapy mobilized circulating stem cells and improved delayed encephalopathy after acute carbon monoxide poisoning with up-regulation of brain-derived neurotrophic factor.

Background Delayed encephalopathy (DE) is the most severe complication after acute carbon monoxide (CO) poisoning, which seriously affects the outcome of patients and leads to a high disability rate. Prior studies have shown that hyperbaric oxygen (HBO2) therapy is therapeutic for DE due to reducing immune-mediated neuropathology and thus improving cognitive performance. Methods In our present perspective study, five DE patients were treated regularly with HBO2 therapy. The mini-mental state examination (MMSE) and Barthel index (BI) were intermittently collected during their hospitalization for mental and physical status evaluation, the peripheral bloods were serially sampled to determine the concentration changes of circulating stem cells, as well as corresponding BDNF and neural markers. Results MMSE and BI showed series of improvements after multiple HBO2 therapies. The CD34+/CD90+ and CD34+/CD133+ dual positive cells, which were categorized as circulating stem cells, were observed an overall up-regulation since the beginning of the DE onset upon the application of HBO2 therapy. Characteristic neurotrophin BDNF, neural markers such as nestin and synaptophysin (SYP) were also up-regulated after exposure of HBO2. Conclusion The application of HBO2 therapy is of significance in improving the cognition of DE patients, along with mobilized circulating stem cells. We primarily infer that the CD34+/CD90+ and CD34+/CD133+ cells were mobilized by HBO2 exposure and have played a positive role in cognition improvement on DE patients by up-regulation of BDNF, nestin and SYP. The altering amount of circulating stem cells mobilized in peripheral blood could be a potential marker on predicting the outcome of DE.

Is serum level of nestin useful in detecting epithelial ovarian cancer?

AIM: The aim of the present study was to evaluate the usefulness of nestin as a discriminative marker between benign and malignant ovarian tumors. METHODS: During the 1 year from January 2015 through December 2015, a nonconsecutive series of 80 patients (40 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Intraoperative frozen section evaluation was performed if there was a suspicion in diagnosis. Statistical analyses were performed using spss ver. 16.0, while clinicopathological variables, including the categorical data, were analyzed using the χ2 -test or Fisher's exact test. A P-value < 0.05 was defined as statistically significant. RESULTS: Preoperative serum carbohydrate antigen (CA)-125, CA-15-3, and nestin levels were significantly higher in the malignant group compared to patients with benign ovarian tumors (P < 0.001, respectively). Serum nestin levels did not differ significantly on the basis of histologic subtypes. Serum nestin levels had specificity of 89.7%, which demonstrates nestin's sufficiency to distinguish benign from malignant epithelial ovarian tumors. The positive likelihood ratio of nestin was found to be superior to that of CA-125 and CA-15-3. CONCLUSION: The results obtained from our study suggest that measurement of nestin level, alongside physical examination, transvaginal ultrasound, and serum CA-125 and CA-15-3 levels, can help differentiate benign ovarian tumors from malignant epithelial ovarian tumors. The findings of our study need to be supported with additional studies.

The Role of Serum Nestin in Diagnosis and Prognosis of Breast Cancer: A Prospective Observational Study.

BACKGROUND/AIM: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer. PATIENTS AND METHODS: Women who underwent surgery for breast cancer at the Breast Unit of the 1st Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens were prospectively included. Patients' demographic data were recorded and serum nestin levels were measured. Molecular biomarker analysis was performed, as well as histopathologic assessment. RESULTS: Seventy patients were included in the analysis. Among patients with breast cancer, 93% were estrogen receptor (ER) positive, 91% were progesterone receptor (PR) positive, and 43% were human epidermal growth factor receptor 2 (HER2) positive. Ki67 was expressed in 16% of patients and p53 was expressed in 32% of patients. Invasive ductal carcinoma was diagnosed in 80% of patients, with 44% of tumors classified as T1 and 46% as T2. Additionally, 43% were G1 and 56% were N0, while 34% were N1. No statistically significant difference was observed between serum nestin levels and ER, PR, HER2, Ki67, and p53 expression. Furthermore, no difference was observed between serum nestin levels and breast cancer histological type, size, N-stage, and grading. CONCLUSION: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced.

Bidirectional Association Between Psoriasis and Obesity: Benefits and Risks.

Psoriasis is a chronic, immune-mediated inflammatory skin disease that is associated with several comorbidities such as obesity. This study was designed to estimate the possibility of utilizing psoriasin, nestin, keratin-16 (Krt16), and interleukin-21 (IL-21) as biochemical markers of psoriasis, to correlate these candidate psoriatic markers with biomarkers of obesity [body mass index (BMI), leptin, and resistin], and to elucidate the bidirectional association between obesity and psoriasis. Blood samples were collected from all participants (n = 108) who were classified according to their BMI into 4 groups: healthy control, obese, psoriatic, and obese psoriatic group. Plasma psoriasin, nestin, Krt16, IL-21, leptin, and resistin were estimated for all subjects. Psoriasin, nestin, Krt16, IL-21, leptin, and resistin were significantly elevated in psoriatic and obese psoriatic groups. However, only leptin, resistin, IL-21, and Krt16 were significantly increased in the obese group compared with the control group. Leptin and resistin showed significant positive correlations with psoriasis area and severity index score, psoriasin, nestin, Krt16, and IL-21. Cutoff values for psoriasin, nestin, Krt16, and IL-21 were 187.5 ng/mL, 1825 pg/mL, 33.1 ng/mL, and 128.6 ng/L, respectively. In conclusion, psoriasin, nestin, Krt16, and IL-21 can be utilized as biochemical markers of psoriasis; these psoriatic markers are significantly positively correlated with obesity biomarkers, and obesity can be considered a risk factor and/or consequence of psoriasis.

Role of Glycyrrhizin in the Reduction of Inflammation in Diabetic Kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes. Recent evidence suggests chronic inflammation to be one of the causal factors of DKD. The mechanisms entailed are not completely elucidated except that a variety of cytokines play a major role in this process. High mobility group box 1 (HMGB1) is a pro-inflammatory toll-like receptor-4 (TLR4)-binding cytokine that is involved in inflammation-associated gene expression. This investigation was designed to assess the involvement of HMGB1, TLR-4, and nuclear factor (NF)-κB in the development of DKD and to evaluate that whether blocking HMGB1 by its natural inhibitor Glycyrrhizin (GLC) can reduce the progression of the disease. METHODS: Studies were carried out in 8-10-weeks old Zucker diabetic fatty (ZDF) and lean, age- and gender-matched rats. At 10 weeks of age, ZDF rats as compared to controls, showed hyperglycemia, without proteinuria. After 8-10 weeks of the development of diabetes, ZDF animals that showed proteinuria were treated with GLC for 4 weeks. In addition, normal rat kidney (NRK-52E) cells with epithelial-like morphology were comparatively treated with GLC under hyperglycemic condition in vitro. RESULTS: Substantial increase in the expression of HMGB1, TLR4, and NF-κB in vivo and in vitro under hyperglycemic conditions was observed as compared to normoglycemic conditions. The overexpression of HMGB1, TLR4, NF-κB, and glomerular injury marker nestin was significantly ameliorated by GLC administration. CONCLUSION: Our findings suggest that hyperglycemia-induced HMGB1 activation in ZDF rats may contribute to the progression of DKD.

Prognostic value of erythrocyte sedimentation rate and C-reactive protein in the blood of patients with glioma.

AIM: To determine any correlation between inflammation parameters in blood glioma patients, with some of the established glioma biomarkers and to evaluate the possible prognostic impact of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for patient survival. PATIENTS AND METHODS: This retrospective study evaluated ESR values in 94 patients and measured CRP values prior to the excision of primary glioma in 165 patients. Overall survival probabilities were determined separately for all patients with glioma in low-grade glioma (LGG), high-grade (HGG) and in glioblastoma multiforme (GBM) using the Kaplan-Meier log-rank test. The correlation between blood ESR and CRP values and between immunohistochemical (IHC) assessment of cluster of differentiation-68 (CD68), cathepsin B and nestin were evaluated. RESULTS: An ESR above 15 mm/h was significant for poor survival prognosis for patients overall (p<0.001) and in the HGG (p<0.01) and GBM (p<0.04) subgroups. A serum CRP level above 5 mg/l was also identified as prognostic in patients overall (p<0.01), and in the HGG (p=0.02) and GBM (p=0.04) subgroups. CONCLUSION: Correlations of ESR and serum levels of CRP have been revealed with prognostic tissue biomarkers i.e. cathepsin B, nestin, CD68. Moreover, preoperative measurement of both parameters could be used for survival prognosis in patients with glioma.