Globally, oral cavity squamous cell carcinoma (OSCC) is one of the most common fatal illnesses. Its high mortality is ascribed to the fact that the disease is often diagnosed at a late stage, which ...indicates an urgent need for approaches for the early detection of OSCC. The use of salivary autoantibodies (autoAbs) as OSCC biomarkers has numerous advantages such as easy access to saliva samples and efficient detection of autoAbs using well‐established secondary reagents. To improve OSCC screening, we identified OSCC‐associated autoAbs with the enrichment of salivary autoAbs combined with affinity mass spectrometry (MS). The salivary IgA of healthy individuals and OSCC patients was purified with peptide M‐conjugated beads and then applied to immunoprecipitated antigens (Ags) in OSCC cells. Using tandem MS analysis and spectral counting‐based quantitation, the level of 10 Ags increased in the OSCC group compared with the control group. Moreover, salivary levels of autoAbs to the 10 Ags were determined by a multiplexed bead‐based immunoassay. Among them, seven were significantly higher in early‐stage OSCC patients than in healthy individuals. A marker panel consisting of autoAbs to LMAN2, PTGR1, RAB13, and UQCRC2 was further developed to improve the early diagnosis of OSCC.
We unveil a new luminescent assay using 11-mercaptoundecanoic acid-bound Au nanodots (11-MUA-Au NDs) for the highly selective and sensitive detection of hydrogen peroxide and glucose, based on ...luminescence quenching.
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation ...potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.
Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are commonly used perfluorinated chemicals (PFCs). PFCs are mainly excreted by urine. Uremic patients tend to accumulate toxins in ...their body and have poor functional status. We investigated the associations between PFCs and the clinical profile of uremic patients under hemodialysis (HD). Liquid chromatography tandem mass spectrometry coupled with isotope dilution was used to quantify PFOA and PFOS. We enrolled 126 patients under regular HD. Compared with previous research, the concentration of PFOA was lower, but that of PFOS was higher in uremic patients than in the general population. The levels of PFOA and PFOS in uremic patients before dialysis were 0.52 (ng/ml) and 21.84 (ng/ml) respectively. The PFOA level remained unchanged but that of PFOS decreased to1.85 ng/mL after dialysis. PFOS can be removed by HD. Patients using hypertensive medication had a lower PFOS then those who did not. The PFOS level was negatively correlated with the duration of the HD session and patient performance status, but positively correlated with levels of cholesterol, chloride (an indicator of acidemia), ferritin, and total protein. (p<0.05). The association with serum protein may explain the long half-life of PFCs in humans. This is the first study which investigated PFCs in uremic patients and showed PFCs are associated with adverse effects in this population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims
Differentiation antagonizing non‐protein coding RNA is associated with various types of neoplasms. Hepatitis C virus‐related hepatocellular carcinoma has a high risk of recurrence. ...Here we determined the role of differentiation antagonizing non‐protein coding RNA in hepatitis C virus‐related hepatocarcinogenesis and identified potential therapeutic targets and non‐invasive prognostic markers for long‐term outcome of hepatitis C virus‐related hepatocellular carcinoma after surgical resection.
Methods
Differentiation antagonizing non‐protein coding RNAs relevant to hepatitis C virus‐related hepatocellular carcinoma were identified through comparative RNA‐sequencing of tumour and adjacent non‐tumour (ANT) tissues in a screening set, and were validated using real‐time polymerase chain reaction. Target long non‐coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus‐related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012.
Results
We confirmed that differentiation antagonizing non‐protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus‐related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus‐related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non‐protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3‐11.6 and 2.7/1.5‐5.1 respectively).
Conclusions
Differentiation antagonizing non‐protein coding RNA is highly relevant to disease progression of hepatitis C virus‐related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non‐protein coding RNA might serve as a non‐invasive prognostic biomarker for hepatitis C virus‐related hepatocellular carcinoma.
Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that modulates cellular redox homeostasis via the regeneration of NADPH. G6PD-deficient cells ...have a reduced ability to induce the innate immune response, thus increasing host susceptibility to pathogen infections. An important part of the immune response is the activation of the inflammasome. G6PD-deficient peripheral blood mononuclear cells (PBMCs) from patients and human monocytic (THP-1) cells were used as models to investigate whether G6PD modulates inflammasome activation. A decreased expression of IL-1β was observed in both G6PD-deficient PBMCs and PMA-primed G6PD-knockdown (G6PD-kd) THP-1 cells upon lipopolysaccharide (LPS)/adenosine triphosphate (ATP) or LPS/nigericin stimulation. The pro-IL-1β expression of THP-1 cells was decreased by G6PD knockdown at the transcriptional and translational levels in an investigation of the expression of the inflammasome subunits. The phosphorylation of p38 MAPK and downstream c-Fos expression were decreased upon G6PD knockdown, accompanied by decreased AP-1 translocation into the nucleus. Impaired inflammasome activation in G6PD-kd THP-1 cells was mediated by a decrease in the production of reactive oxygen species (ROS) by NOX signaling, while treatment with hydrogen peroxide (H2O2) enhanced inflammasome activation in G6PD-kd THP-1 cells. G6PD knockdown decreased Staphylococcus aureus and Escherichia coli clearance in G6PD-kd THP-1 cells and G6PD-deficient PBMCs following inflammasome activation. These findings support the notion that enhanced pathogen susceptibility in G6PD deficiency is, in part, due to an altered redox signaling, which adversely affects inflammasome activation and the bactericidal response.
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Effective antiviral therapeutics are urgently required to fight severe acute respiratory syndrome (SARS) caused by a SARS coronavirus (SARS-CoV). Because polyphenol catechins could confer ...antioxidative, anti-inflammatory, antiviral, and antimicrobial activities, we assessed the therapeutic effects of catechins against SARS-CoV replication in Vero E6 cells, the preventive effect of catechins on CD25/CD69/CD94/CD8+ cytotoxic T lymphocytes-mediated adaptive immunity, and the protective effect on lipopolysaccharide-induced acute lung injury (ALI) in mice. We found that catechins containing 32.8% epigallocatechin gallate, 15.2% epicatechin gallate, 13.2 epicatechin, 10.8% epigallocatechin, 10.4% gallocatechin, and 4.4% catechin directly inhibited SARS-CoV replication at sub-micromolecular concentrations. Four-week catechins ingestion increased CD8+ T cell percentage, upregulated CD69+/CD25+/CD94-NKG2A/CD8+ T lymphocytes-mediated adaptive immunity, and increased type I cytokines release responding to ovalbumin/alum. Catechins significantly reduced lipopolysaccharide-induced cytokine storm and oxidative stress and ALI by inhibiting PI3K/AKT/mTOR signaling to upregulate Beclin-1/Atg5-Atg12/LC3-II-mediated autophagy mechanism. Pretreatment of autophagy inhibitor 3-Methyladenine reversed the inhibiting effects of catechins on the cytokines and oxidative stress levels and ALI. In conclusion, our data indicated that catechins directly inhibited SARS-CoV replication, potentiated the CD25/CD69/CD94/CD8+ T lymphocytes-mediated adaptive immunity and attenuated lipopolysaccharide-induced ALI and cytokine storm by PI3K/AKT/mTOR-signaling-mediated autophagy, which may be applied to prevent and/or treat SARS-CoV infection.
A colorimetric, label-free, and nonaggregation-based gold nanoparticles (Au NPs) probe has been developed for the detection of Pb2+ in aqueous solution, based on the fact that Pb2+ ions accelerate ...the leaching rate of Au NPs by thiosulfate (S2O3 2−) and 2-mercaptoethanol (2-ME). Au NPs reacted with S2O3 2− ions in solution to form Au(S2O3)2 3− complexes on the Au NP surfaces, leading to slight decreases in their surface plasmon resonance (SPR) absorption. Surface-assisted laser desorption/ionization time-of-flight ionization mass spectrometry (SALDI-TOF MS) data reveals the formation of Pb−Au alloys on the surfaces of the Au NPs in the presence of Pb2+ ions and 2-ME. The formation of Pb−Au alloys accelerated the Au NPs rapidly dissolved into solution, leading to dramatic decreases in the SPR absorption. The 2-ME/S2O3 2−-Au NP probe is highly sensitive (LOD = 0.5 nM) and selective (by at least 1000-fold over other metal ions) toward Pb2+ ions, with a linear detection range (2.5 nM−10 μM) over nearly 4 orders of magnitude. The cost-effective probe allows rapid and simple determination of the concentrations of Pb2+ ions in environmental samples (Montana soil and river), with results showing its great practicality for the detection of lead in real samples.
Aims and objectives
To determine prehospitalised diabetes‐related foot ulcer (DFU) self‐management behaviours and explore the factors associated with these behaviours.
Background
Although there are ...many studies that explore DFU prevention and treatment, to our knowledge, there are no quantitative studies of DFU self‐management behaviours.
Design
Cross‐sectional design.
Methods
From June 2015–June 2016, 199 hospitalised patients with DFU were given a survey questionnaire at a medical centre in northern Taiwan. DFU self‐management behaviours, diabetes foot self‐care behaviours, beliefs in regard to barriers to DFU self‐management behaviours, and knowledge regarding warning signs of DFU deterioration were assessed by well‐designed measurement tools. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used to ensure quality reporting during this observational study (see Supporting Information Appendix S1).
Results
The results revealed that 62.8% of participants never monitored their blood glucose level when they had foot ulcers, and 63.8% never sought treatment for their wounds when their wounds were not painful. After controlling for demographic and medical variables, stepwise multiple regression analysis revealed that the following eight significant variables were associated with DFU self‐management behaviours: two DFU self‐management barrier beliefs, foot self‐care behaviour, no treatment for diabetes, poor financial status, employment, knowledge regarding the warning signs of DFU deterioration, and number of DFU hospitalisations.
Conclusions
Diabetes‐related foot ulcer self‐management behaviours were insufficient. Some modifiable factors and high‐risk groups for insufficient DFU self‐management behaviour were identified.
Relevance to clinical practice
Diabetes‐related foot ulcer self‐management behaviours should be promoted. Interventions that modify the risk factors that were identified in this study can be designed to promote the performance of DFU self‐management behaviours.
CO2 has been reported to be absorbed from the bowel more rapidly than air, resulting in a discomfort reduction after colonoscopy. Its role in deeply sedated patients is limited. This study was ...designed to investigate the efficacy and safety of CO2 insufflation during colonoscopy in patients deeply sedated with propofol.
A total of 125 continuous patients were randomly assigned to receive either CO2 (n = 63) or air (n = 62) insufflation during propofol-sedated colonoscopy. Postcolonoscopy abdominal pain, distention, and satisfaction were assessed at 1, 3, and 24 h after the procedure, and the proportions of pain-free and distention-free patients were compared. Residual bowel gas in the colon and small bowel was evaluated at 1 h after colonoscopy. End-tidal CO2 and O2 saturation was measured for safety analysis.
There was a significant difference between the two groups regarding the postcolonoscopy abdominal pain, distention, and subjective satisfaction at 1 h (P < 0.001) and 3 h (P < 0.01) after the procedure. Patients' pain and distention at 1 and 3 h after the procedure were significantly lower in the CO2 group (P < 0.01). Residual bowel gas in the colon and small bowel was significantly less in the CO2 group (P < 0.001). There was no significant difference in end-tidal CO2 levels between two groups before, during, and after the procedure.
Compared with air, CO2 insufflation during colonoscopy reduced postcolonoscopy abdominal discomfort and improved patients' satisfaction. It was safe to use CO2 insufflation in deeply sedated colonoscopy.
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