OX133, a monoclonal antibody recognizing protein-bound N-ethylmaleimide for the identification of reduced disulfide bonds in proteins

In vivo, enzymatic reduction of some protein disulfide bonds, allosteric disulfide bonds, provides an important level of structural and functional regulation. The free cysteine residues generated can be labeled by maleimide reagents, including biotin derivatives, allowing the reduced protein to be detected or purified. During the screening of monoclonal antibodies for those specific for the reduced forms of proteins, we isolated OX133, a unique antibody that recognizes polypeptide resident, N-ethylmaleimide (NEM)-modified cysteine residues in a sequence-independent manner. OX133 offers an alternative to biotin-maleimide reagents for labeling reduced/alkylated antigens and capturing reduced/alkylated proteins with the advantage that NEM-modified proteins are more easily detected in mass spectrometry, and may be more easily recovered than is the case following capture with biotin based reagents

Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive–behavioural therapy-based psychoeducation and usual care. Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms

A longitudinal evaluation of psychosocial changes throughout orthognathic surgery.

BACKGROUND:Jaw correction surgery can cause significant psychosocial impacts on patients. This prospective study investigated the longitudinal changes of psychosocial characteristics of patients with dentofacial deformities after jaw correction surgery and the factors that predict the psychological resilience in Hong Kong Chinese undergoing jaw correction surgery. METHODS:A longitudinal cohort study was conducted on 92 Hong Kong Chinese patients (32 males, 60 females; mean age = 24.75 ± 5.65 years), who had jaw correction surgery as treatment for their dentofacial deformities, from 1st June 2011 to 30th June 2015. Self-completed psychological inventories including Brief Symptom Inventory, Life Orientation Test, and the Adult Trait Hope Scale were used to measure distress, optimism, and hope levels respectively. Patients completed the inventories in five time points: the surgical consent signing day (usually two to three months before the surgery) (T1); one day before operation (T2), first to second post-operative week (T3), third post-operative month (T4) and sixth post-operative month (T5). RESULTS:Latent class growth analysis revealed two outcome trajectory classes: a resilience trajectory (n = 45, 48.9%) and a chronic dysfunction trajectory (n = 14, 15.2%). Another 33 (35.9%) showed erratic trajectory patterns that would not be classified into any categories. The psychological distress levels of patients in the resilience trajectory group, on average, were below the clinical threshold of the Brief Symptom Inventory at all time points. However, the opposite result was obtained for patients in the chronic dysfunctional group. Patients exhibiting a resilience trajectory pattern, when compared to those showing a chronic dysfunction pattern, had higher optimism (t(57) = 3.69, p < .0001) and hope (t(57) = 2.46, p < .05) levels at T1. Logistic regression analyses were conducted to compare the relative power of optimism and hope levels at T1 to predict resilience or chronic dysfunctional group membership. A test of the full model against a constant only model was statistically significant (χ2(2) = 24.096, p < .01). Preoperative baseline optimism (B = -.276, p < .05) but not hope (B = -.25, ns) was a significant variable to classify the outcome trajectories for psychological distress. CONCLUSIONS:Most patients were resilient to dentofacial deformities jaw correction surgery. About 15% exhibited a chronic distress pattern. An optimistic view about the surgery may enhance resilience. Pre-surgical counselling or educational sessions to facilitate a realistic positive outlook about the operation would be beneficial

MAEL Augments Cancer Stemness Properties and Resistance to Sorafenib in Hepatocellular Carcinoma through the PTGS2/AKT/STAT3 Axis

Cancer stem cells (CSCs) are responsible for tumorigenesis, therapeutic resistance, and metastasis in hepatocellular cancer (HCC). Cancer/testis antigen Maelstrom (MAEL) is implicated in the formation of CSC phenotypes, while the exact role and underlying mechanism remain unclear. Here, we found the upregulation of MAEL in HCC, with its expression negatively correlated with survival outcome. Functionally, MAEL promoted tumor cell aggressiveness, tumor stem-like potentials, and resistance to sorafenib in HCC cell lines. Transcriptional profiling indicated the dysregulation of stemness in MAEL knockout cells and identified PTGS2 as a critical downstream target transactivated by MAEL. The suppression effect of MAEL knockout in tumor aggressiveness was rescued in PTGS2 overexpression HCC cells. A molecular mechanism study revealed that the upregulation of PTGS2 by MAEL subsequently resulted in IL-8 secretion and the activation of AKT/NF-κB/STAT3 signaling. Collectively, our work identifies MAEL as an important stemness regulation gene in HCC. Targeting MAEL or its downstream molecules may provide a novel possibility for the elimination of CSC to enhance therapeutic efficacy for HCC patients in the future

Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients

Background/Aims: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. Methods: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. Results: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p Conclusion: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients

Circulating Tumor Cell Enumeration for Serial Monitoring of Treatment Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma

We aim to reveal the clinical significance and potential usefulness of dynamic monitoring of CTCs to track therapeutic responses and improve survival for advanced ESCC patients. Peripheral blood (PB) (n = 389) and azygos vein blood (AVB) (n = 13) samplings were recruited prospectively from 88 ESCC patients undergoing curative surgery from 2017 to 2022. Longitudinal CTC enumeration was performed with epithelial (EpCAM/pan-cytokeratins/MUC1) and mesenchymal (vimentin) markers at 12 serial timepoints at any of the pre-treatment, all of the post-treatments/pre-surgery, post-surgery follow-ups for 3-year, and relapse. Longitudinal real-time CTC analysis in PB and AVB suggests more CTCs are released early at pre-surgery and 3-month post-surgery into the circulation from the CTRT group compared to the up-front surgery group. High CTC levels at pre-treatments, 1-/3-month post-surgery, unfavorable changes of CTC levels between all post-treatment/pre-surgery and 1-month or 3-month post-surgery (Hazard Ratio (HR) = 6.662, p &lt; 0.001), were independent prognosticators for curative treatment. The unfavorable pre-surgery CTC status was independent prognostic and predictive for neoadjuvant treatment efficacy (HR = 3.652, p = 0.035). The aggressive CTC clusters were more frequently observed in AVB compared to PB. Its role as an independent prognosticator with relapse was first reported in ESCC (HR = 2.539, p = 0.068). CTC clusters and longitudinal CTC monitoring provide useful prognostic information and potential predictive biomarkers to help guide clinicians in improving disease management

Circulating Tumor Cell Enumeration for Serial Monitoring of Treatment Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma

We aim to reveal the clinical significance and potential usefulness of dynamic monitoring of CTCs to track therapeutic responses and improve survival for advanced ESCC patients. Peripheral blood (PB) (n = 389) and azygos vein blood (AVB) (n = 13) samplings were recruited prospectively from 88 ESCC patients undergoing curative surgery from 2017 to 2022. Longitudinal CTC enumeration was performed with epithelial (EpCAM/pan-cytokeratins/MUC1) and mesenchymal (vimentin) markers at 12 serial timepoints at any of the pre-treatment, all of the post-treatments/pre-surgery, post-surgery follow-ups for 3-year, and relapse. Longitudinal real-time CTC analysis in PB and AVB suggests more CTCs are released early at pre-surgery and 3-month post-surgery into the circulation from the CTRT group compared to the up-front surgery group. High CTC levels at pre-treatments, 1-/3-month post-surgery, unfavorable changes of CTC levels between all post-treatment/pre-surgery and 1-month or 3-month post-surgery (Hazard Ratio (HR) = 6.662, p p = 0.035). The aggressive CTC clusters were more frequently observed in AVB compared to PB. Its role as an independent prognosticator with relapse was first reported in ESCC (HR = 2.539, p = 0.068). CTC clusters and longitudinal CTC monitoring provide useful prognostic information and potential predictive biomarkers to help guide clinicians in improving disease management

Major trauma care in Hong Kong and Germany: a trauma registry data benchmark study

Background Trauma remains a leading cause of death and effective trauma management within a well-developed trauma system has been shown to reduce morbidity and mortality. A trauma registry, as an integral part of a mature trauma system, can be used to monitor the quality of trauma care and to provide a means to compare local versus international standards. Hong Kong and Germany both have highly developed health care services. We compared the performance of trauma systems including outcomes among major trauma victims (ISS > 15) over a 3-year period (2013-2015) in both settings using trauma registry data. Methods This study was a retrospective analysis of prospectively collected data from trauma registries in Hong Kong and Germany. Data from 01/2013 to 12/2015 were extracted from the trauma registries of the five trauma centers in Hong Kong and the TraumaRegister DGU(R) (TR-DGU). The study cohort included adults (>= 18 years) with major trauma (ISS > 15). Data related to patient characteristics, nature of the injury, prognostic parameters to calculate the RISC II score, outcomes and clinical management were collected and compared. Results Datasets from 1,864 Hong Kong and 10,952 German trauma victims were retrieved from respective trauma registries. The unadjusted mortality in Hong Kong (22.4%) was higher compared to Germany (19.2%); the difference between observed and expected mortality was higher in Hong Kong (+ 2.7%) than in Germany (- 0.5%). The standardized mortality ratio (SMR) in Hong Kong and Germany were 1.138 (95% CI 1.033-1.252) and 0.974 (95% CI 0.933-1.016), respectively, and the adjusted death rate in Hong Kong was significantly higher compared to the calculated RISC II data. However, patients in Hong Kong were significantly older, had more pre-trauma co-morbidities, more head injuries, shorter hospital and ICU stays and lower ICU admission rates. Conclusion Hong Kong had a higher mortality rate and a statistically significantly higher standardized mortality ratio (SMR) after RISC II adjustment. However, multiple differences existed between trauma systems and patient characteristics