A colorimetric and fluorescent signaling probe for assaying Pd2+ in practical samples.

We developed an optical signaling probe to detect Pd2+ ions in Pd-containing catalyst and drug candidate. The Pd2+ signaling probe (Res-DT) was readily prepared by reacting the versatile fluorochrome resorufin with phenyl chlorodithioformate. In a phosphate-buffered saline solution (pH 7.4) containing sodium dodecyl sulfate (SDS) as a signal-boosting surfactant, Res-DT exhibited a pronounced colorimetric response with a chromogenic yellow to magenta shift, leading to a substantial increase in the fluorescence intensity. The Pd2+ signaling performance of Res-DT was attributed to the Pd2+-promoted hydrolysis of the dithioate moiety. The probe displayed high selectivity toward Pd2+ ions and remained unaffected by commonly encountered coexisting components. Moreover, the detection limit of Res-DT for Pd2+ ions was 10 nM, and the signaling was achieved within 7 min. Furthermore, to demonstrate the real-world applicability of Res-DT, a Pd2+ assay was performed in Pd-containing catalyst and drug candidate using an office scanner as an easily accessible measurement device. Our results highlight the prospects of Res-DT as a tool to detect Pd2+ ions in various practical samples, with potential applications in catalysis, medicine, and environmental science.

Effects of high versus low inspiratory oxygen fraction on postoperative clinical outcomes in patients undergoing surgery under general anesthesia: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To determine whether high perioperative inspired oxygen fraction (FiO2) compared with low FiO2 has more deleterious postoperative clinical outcomes in patients undergoing non-thoracic surgery under general anesthesia. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Operating room, postoperative recovery room and surgical ward. PATIENTS: Surgical patients under general anesthesia. INTERVENTION: High perioperative FiO2 (≥0.8) vs. low FiO2 (≤0.5). MEASUREMENTS: The primary outcome was mortality within 30 days. Secondary outcomes were pulmonary outcomes (atelectasis, pneumonia, respiratory failure, postoperative pulmonary complications [PPCs], and postoperative oxygen parameters), intensive care unit (ICU) admissions, and length of hospital stay. A subgroup analysis was performed to explore the treatment effect by body mass index (BMI). MAIN RESULTS: Twenty-six trials with a total 4991 patients were studied. The mortality in the high FiO2 group did not differ from that in the low FiO2 group (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.42-1.97, P = 0.810). Nor were there any significant differences between the groups in such outcomes as pneumonia (RR 1.19, 95% CI 0.74-1.92, P = 0.470), respiratory failure (RR 1.29, 95% CI 0.82-2.04, P = 0.270), PPCs (RR 1.05, 95% CI 0.69-1.59, P = 0.830), ICU admission (RR 0.94, 95% CI 0.55-1.60, P = 0.810), and length of hospital stay (mean difference [MD] 0.27 d, 95% CI -0.28-0.81, P = 0.340). The high FiO2 was associated with postoperative atelectasis more often (risk ratio 1.27, 95% CI 1.00-1.62, P = 0.050), and lower postoperative arterial partial oxygen pressure (MD -5.03 mmHg, 95% CI -7.90- -2.16, P < 0.001). In subgroup analysis of BMI >30 kg/m2, these parameters were similarly affected between the groups. CONCLUSIONS: The use of high FiO2 compared to low FiO2 did not affect the short-term mortality, although it may increase the incidence of atelectasis in adult, non-thoracic patients undergoing surgical procedures. Nor were there any significant differences in other secondary outcomes.

Downregulation of WNT11 is associated with bladder tissue fibrosis in patients with interstitial cystitis/bladder pain syndrome without Hunner lesion.

This study assessed the functional role of WNT genes and the association between WNT signalling cascades and fibrosis in interstitial cystitis/bladder pain syndrome (IC/BPS) patients. Twenty-five patients (3 males, 22 females; mean age 59.7 ± 10.9 years), included 7 non-Hunner-type IC (NHIC), 18 Hunner-type IC (HIC), and 5 non-IC (control) groups. The expression of sonic hedgehog, WNT gene family, and genes previously reported as biomarkers for IC/BPS were examined using RT-PCR in biopsy specimens from the mucosa and submucosa layer of the bladder. WNT2B, WNT5A, WNT10A, and WNT11 functions in the urothelium were evaluated by silencing in an HBlEpC cell line. Pelvic Pain and Urgency/Frequency Patient Symptom Scale scores, O'Leary-Sant Symptom and Problem Index scores, and Visual Analogue Scores did not differ between the NHIC and HIC groups. However, HIC patients had significantly shorter symptom duration (30.9 vs 70.8 months, p = 0.046), higher daily urinary frequency (16.1 versus 8.5 times, p = 0.006), and smaller bladder capacity (208.6 versus 361.4 ml, p = 0.006) than NHIC patients. Overall WNT gene expression was lower in NHIC than HIC patients. Bladder epithelial tissues from HIC patients were characterised by the downregulation of WNT11. Silencing of WNT11, WNT2B, WNT5A, and WNT10A in HBlEpCs resulted in fibrotic changes, indicated by fibrotic morphology, increased fibrosis-related gene expression, and nuclear localisation of phosphorylated SMAD2, and increased vimentin and fibronectin levels. Downregulation of WNT11 results in fibrotic changes of bladder epithelial cells and is associated with the pathogenesis and differential diagnosis of NHIC. Decreased expression of WNT11 is a potential biomarker for predicting NHIC.

The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats.

PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem cell (hESC)-derived multipotent stem cells (M-MSCs) than adult bone-marrow (BM)-derived counterparts for treating IC/BPS and also monitor long-term safety and in vivo properties of transplanted M-MSCs in living animals. Controlled hESC differentiation and isolation procedures resulted in pure M-MSCs displaying typical MSC behavior. In a hydrochloric-acid instillation-induced IC/BPS animal model, a single local injection of M-MSCs ameliorated bladder symptoms of IC/BPS with superior efficacy compared to BM-derived MSCs in ameliorating bladder voiding function and histological injuries including urothelium denudation, mast-cell infiltration, tissue fibrosis, apoptosis, and visceral hypersensitivity. Little adverse outcomes such as abnormal growth, tumorigenesis, or immune-mediated transplant rejection were observed over 12-months post-injection. Intravital confocal fluorescence imaging tracked the persistence of the transplanted cells over 6-months in living animals. The infused M-MSCs differentiated into multiple cell types and gradually integrated into vascular-like structures. The present study provides the first evidence for improved therapeutic efficacy, long-term safety, and in vivo distribution and cellular properties of hESC derivatives in preclinical models of IC/BPS.

Histopathological characteristics of interstitial cystitis/bladder pain syndrome without Hunner lesion.

AIMS: To assess the distinct histopathological characteristics and their clinical significance between non-Hunner-type and Hunner-type interstitial cystitis (IC)/bladder pain syndrome (BPS). METHODS AND RESULTS: We prospectively enrolled and classified IC/BPS patients, on the basis of cystoscopic findings, as having non-Hunner-type IC and Hunner-type IC. Specimens obtained from the posterior wall in non-Hunner-type IC cases during hydrodistension or from Hunner/non-Hunner lesions in Hunner-type IC cases during transurethral resection were evaluated. Stress urinary incontinence patients with microscopic haematuria were selected as controls. Biopsy specimens were obtained from 15 non-Hunner-type IC, 15 Hunner-type IC and 5 non-IC patients. Severe and moderate fibrosis was more frequently observed in non-Hunner-type IC than in Hunner-type IC and non-IC cases. However, severe and moderate inflammation was more frequently observed in Hunner-type IC than in non-Hunner-type IC cases. The remnant urothelium was significantly decreased in Hunner-type IC cases as compared with non-Hunner-type IC and non-IC cases (P < 0.05), and non-Hunner-type IC cases showed a higher number of mast cells than Hunner-type IC and non-IC cases (P = 0.035). Accordingly, several fibrosis-promoting genes were highly expressed in bladder tissues of non-Hunner-type IC, as compared with Hunner-type IC. Patients with severe fibrosis showed significantly higher urinary frequency and smaller bladder capacity than those with moderate and mild fibrosis (all P < 0.05). CONCLUSIONS: Non-Hunner-type IC is characterized by severe fibrosis and increased mast cell infiltration, whereas Hunner-type IC is characterized by severe inflammation and urothelial denudation in the entire bladder. Fibrosis in the bladder of IC/BPS patients was correlated with increased urinary frequency and decreased bladder capacity.

Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (ß = 0.001, P < 0.001), serum triglyceride (ß = 0.001, P < 0.001), CCr (ß = -0.003, P = 0.001), hsCRP (ß = 0.157, P = 0.001), fibrinogen (ß = 0.001, P < 0.001) and BMI (ß = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.