The relationship between Cd‐induced autophagy and lysosomal activation in WRL‐68 cells

This study shows that Cd induces autophagy in the human's embryonic normal liver cell line (WRL‐68). The expression of LC3B‐II and the mature cathepsin L were analyzed by Western blotting. The autophagosomes and lysosomes were directly visualized by electron microscopy and confocal microscopy analysis in Cd‐exposed WRL‐68 cells. In this study, we first found that autophagy induced the activation of lysosomal function in WRL‐68 cells. The lysosomal activation was markedly decreased when the cells were co‐treated with 3‐MA (an inhibitor of autophagy). Secondly, we provided the evidence that the activation of lysosomal function depended on autophagosome–lysosome fusion. The colocalization of lysosome‐associated membrane protein‐2 (LAMP2) and GFP‐LC3 was significantly reduced, when they were treated with thapsigargin (an inhibitor of autophagosome–lysosome fusion). We demonstrated that deletion or blockage of the autophagosome–lysosome fusion process effectively diminished lysosomal activation, which suggests that lysosomal activation occurring in the course of autophagy is dependent on autophagosome–lysosome fusion. Thirdly, we provided evidence that the activation of lysosomal function was associated with lysosomal acid. We investigated the relationship between autophagosome–lysosome fusion and pH in acidic compartments by visualizing fusion process in WRL‐68 cells. This suggests that increasing pH in acidic compartments in WRL‐68 cells inhibits the autophagosome–lysosome fusion. Finally, we found that the activation of lysosomal function was associated with Ca²⁺ stores and the intracellular Ca²⁺ channels or pumps were possibly pH‐dependent. Copyright © 2015 John Wiley & Sons, Ltd.     

Systematic review on the prevalence,frequency and comparative value of adverse events data in social media

Aim

The aim of this review was to summarize the prevalence, frequency and comparative value of information on the adverse events of healthcare interventions from user comments and videos in social media.

Methods

A systematic review of assessments of the prevalence or type of information on adverse events in social media was undertaken. Sixteen databases and two internet search engines were searched in addition to handsearching, reference checking and contacting experts. The results were sifted independently by two researchers. Data extraction and quality assessment were carried out by one researcher and checked by a second. The quality assessment tool was devised in-house and a narrative synthesis of the results followed.

Results

From 3064 records, 51 studies met the inclusion criteria. The studies assessed over 174 social media sites with discussion forums (71%) being the most popular. The overall prevalence of adverse events reports in social media varied from 0.2% to 8% of posts.Twenty-nine studies compared the results from searching social media with using other data sources to identify adverse events. There was general agreement that a higher frequency of adverse events was found in social media and that this was particularly true for ‘symptom’ related and ‘mild’ adverse events.Those adverse events that were under-represented in social media were laboratory-based and serious adverse events.

Conclusions

Reports of adverse events are identifiable within social media. However, there is considerable heterogeneity in the frequency and type of events reported, and the reliability or validity of the data has not been thoroughly evaluated.     

Photoluminescence mechanism and applications of Zn-doped carbon dots

Heteroatom-doped carbon dots (CDs) with excellent optical characteristics and negligible toxicity have emerged in many applications including bioimaging, biosensing, photocatalysis, and photothermal therapy. The metal-doping of CDs using various heteroatoms results in an enhancement of the photophysics but also imparts them with multifunctionality. However, unlike nonmetal doping, typical metal doping results in low fluorescence quantum yields (QYs), and an unclear photoluminescence mechanism. In this contribution, we detail results concerning zinc doped CDs (Zn-CDs) with QYs of up to 35%. The zinc ion charges serve as a surface passivating agent and prevent the aggregation of graphene π–π stacking, leading to an increase in the QY of the Zn-CDs. Structural and chemical investigations using spectroscopic and first principle simulations further revealed the effects of zinc doping on the CDs. The robust Zn-CDs were used for the ultra-trace detection of Hg²⁺ with a detection limit of 0.1 μM, and a quench mechanism was proposed. The unique optical properties of the Zn-CDs have promise for use in applications such as in vivo sensing and future phototherapy applications.

Zinc ions, acting as a surface passivating agent, prevented the aggregation of graphene π–π stacking and increased the quantum yield of Zn-carbon dots.     

WS2/g-C3N4 composite as an efficient heterojunction photocatalyst for biocatalyzed artificial photosynthesis

A heterogeneous WS₂/g-C₃N₄ composite photocatalyst was prepared by a facile ultrasound-assisted hydrothermal method. The WS₂/g-C₃N₄ composite was used for photocatalytic regeneration of NAD⁺ to NADH, which were coupled with dehydrogenases for sustainable bioconversion of CO₂ to methanol under visible light irradiation. Compared with pristine g-C₃N₄ and the physical mixture of WS₂ and g-C₃N₄, the fabricated WS₂/g-C₃N₄ composite catalyst with 5 wt% of WS₂ showed the highest activity for methanol synthesis. The methanol productivity reached 372.1 μmol h⁻¹ g_cat⁻¹, which is approximately 7.5 times higher than that obtained using pure g-C₃N₄. For further application demonstration, the activity of the WS₂/g-C₃N₄ composite catalyst toward photodegradation of Rhodamine B (RhB) was evaluated. RhB removal ratio approaching 100% was achieved in 1 hour by using the WS₂/g-C₃N₄ composite catalyst with 5 wt% of WS₂, at an apparent degradation rate approximately 2.6 times higher than that of pure g-C₃N₄. Based on detailed investigations on physiochemical properties of the photocatalysts, the significantly enhanced reaction efficiency of the WS₂/g-C₃N₄ composite was considered to be mainly benefiting from the formation of a heterojunction interface between WS₂ and g-C₃N₄. Upon visible-light irradiation, the photo-induced electrons can transfer from the conduction band of g-C₃N₄ to WS₂, thus recombination of electrons and holes was decreased and the photo-harvesting efficiency was enhanced.

A heterogeneous WS₂/g-C₃N₄ composite photocatalyst was prepared by a facile ultrasound-assisted hydrothermal method.     

The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia

Venetoclax is a promising agent in the treatment of acute myeloid leukemia (AML), though its antileukemic activity is limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways to enhance venetoclax activity. In this study, we combine venetoclax with the dual PI3K and histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, and induce DNA damage, as well as downregulate c-Myc. We establish that CUDC-907 and venetoclax synergistically induce apoptosis in AML cell lines and primary AML patient samples ex vivo. CUDC-907 downregulates CHK1, Wee1, RRM1, and c-Myc, which were found to play a role in venetoclax-induced apoptosis. Interestingly, we find that venetoclax treatment enhances CUDC-907-induced DNA damage potentially through inhibition of DNA repair. In vivo results show that CUDC-907 enhances venetoclax efficacy in an AML cell line derived xenograft mouse model, supporting the development of CUDC-907 in combination with venetoclax for the treatment of AML.     

Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing

BackgroundLeft bundle branch pacing (LBBP) is a novel method for delivering cardiac resynchronization therapy (CRT). We compared on-treatment outcomes with His bundle pacing (HBP) and biventricular pacing (BVP) in this nonrandomized observational study.MethodsConsecutive patients with left-ventricular ejection fraction (LVEF) ≤ 40% and typical left bundle branch block (LBBB) referred for CRT received BVP, HBP, or LBBP. QRS duration, pacing threshold, LVEF, and New York Heart Association (NYHA) class were assessed.ResultsOne hundred thirty-seven patients were recruited: 49 HBP, 32 LBBP, and 54 BVP; 2 did not receive CRT. The majority of patients had nonischemic cardiomyopathy. Mean paced QRS duration was 100.7 ± 15.3 ms, 110.8 ± 11.1 ms, and 135.4 ± 20.2 ms during HBP, LBBP, and BVP, respectively. HBP and LBBP demonstrated a similar absolute increase (Δ) in LVEF (+23.9% vs +24%, P = 0.977) and rate of normalized final LVEF (74.4% vs 70.0%, P = 0.881) at 1-year follow-up. This was significantly higher than in the BVP group (Δ LVEF +16.7% and 44.9% rate of normalized final LVEF, P < 0.005). HBP and LBBP also demonstrated greater improvements in NYHA class compared with BVP. LBBP was associated with higher R-wave amplitude (11.2 ± 5.1 mV vs 3.8 ± 1.9 mV, P < 0.001) and lower pacing threshold (0.49 ± 0.13 V/0.5 ms vs 1.35 ± 0.73 V/0.5 ms, P < 0.001) compared with HBP.ConclusionLBBP appears to be a promising method for delivering CRT. We observed similar improvements in symptoms and LV function with LBBP and HBP. These improvements were significantly greater than those seen in patients treated with BVP in this nonrandomized study. These promising findings justify further investigation with randomized trials.     

Cardiac Rehabilitation Programs for Chronic Heart Disease: A Bayesian Network Meta-analysis

BackgroundCardiac rehabilitation is a medically supervised program after coronary events that involves exercise and dietary modification. We evaluated the comparative benefits and harms of cardiac rehabilitation strategies via a network meta-analysis.MethodsWe followed a pre-specified protocol (PROSPERO: CRD42018094998). We searched Embase, MEDLINE, and Cochrane Central Register of Randomized Trials databases for randomized controlled trials that evaluated cardiac rehabilitation vs a second form of rehabilitation or standard/usual care in adults after myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, or angiography. Risk of bias and evidence quality was evaluated using the Cochrane tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Pairwise and Bayesian network meta-analyses were performed for 11 clinical outcomes.ResultsWe included 134 randomized controlled trials involving 62,322 participants. Compared with standard care, exercise-only cardiac rehabilitation reduced the odds of cardiovascular mortality (odds ratio [OR], 0.70; 95% credibility interval [CrI], 0.51-0.96; moderate-quality evidence), major adverse cardiovascular events (OR, 0.57; 95% CrI, 0.40-0.78; low-quality evidence), nonfatal myocardial infarction (OR, 0.71; 95% CrI, 0.54-0.93; moderate-quality evidence), all-cause hospitalization (OR, 0.74; 95% CrI, 0.54-0.98; moderate-quality evidence), and cardiovascular hospitalization (OR, 0.69; 95% CrI, 0.51-0.88; moderate-quality evidence). Exercise-only cardiac rehabilitation was associated with lower cardiovascular hospitalization risk relative to cardiac rehabilitation without exercise (OR, 0.68; 95% CrI, 0.48-0.97; moderate-quality evidence).ConclusionsCardiac rehabilitation programs containing exercise might provide broader cardiovascular benefits compared with those without exercise.     

Myositis-specific autoantibodies in adults with idiopathic inflammatory myopathy: correlations with diagnosis and disease activity

Clinical Rheumatology - To determine the relationship of myositis autoantibodies with the diagnosis and severity of idiopathic inflammatory myopathy (IIM) using the 2017 EULAR/ACR idiopathic...     

Serum soluble programmed death-1 levels predict the spontaneous HBeAg seroclearance in chronic hepatitis B

Journal of Gastroenterology - In chronic hepatitis B virus (HBV) infection, earlier seroclearance of hepatitis B e antigen (HBeAg) is associated with more favorable outcomes. Soluble programmed...