As lung cancer remains the leading cause of cancer deaths globally, characterizing the tumor molecular profiles is crucial to tailoring treatments for individuals at advanced stages. Cancer cells ...exhibit strong dependence on iron for their proliferation, and several iron-regulatory proteins have been proposed as either oncogenes or tumor suppressive genes. This study aims to evaluate the prospective therapeutic and prognostic values of the sideroflexin (SFXN) gene family, whose functions involve mitochondrial iron metabolism, in lung adenocarcinoma (LUAD). Differential expression analysis using TIMER and UALCAN tools was first employed to compare SFXNs expression levels between normal and LUAD tissues. Next, SFXNs’ prognostic values, biological significance, and potential as immunotherapy candidates were examined from GEPIA, cBioPortal, MetaCore, Cytoscape, and TIMER databases. It was found that all members of SFXN family, except SFXN3, were differentially expressed in LUAD compared to normal samples and within different stages of LUAD. Survival analysis then revealed SFXN1 to be related to worse overall survival outcome in patients with LUAD. Furthermore, several correlations between expression of SFXN1 and immune infiltration cells were discovered. To conclude, our study provides evidence of SFXN family gene’s relevance to the prognosis and immunotherapeutic targets of LUAD.
IMPORTANCE: The efficacy of endovascular thrombectomy (EVT) for symptomatic large anterior vessel occlusion (sLAVO) sharply decreases with time. Because EVT is restricted to comprehensive stroke ...centers, prehospital triage of patients with acute stroke codes for sLAVO is crucial, and although several prediction scales are already in use, external validation, head-to-head comparison, and feasibility data are lacking. OBJECTIVE: To conduct external validation and head-to-head comparisons of 7 sLAVO prediction scales in the emergency medical service (EMS) setting and to assess scale feasibility by EMS paramedics. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted between July 2018 and October 2019 in a large urban center in the Netherlands with a population of approximately 2 million people and included 2 EMSs, 3 comprehensive stroke centers, and 4 primary stroke centers. Participants were consecutive patients aged 18 years or older for whom an EMS-initiated acute stroke code was activated. Of 2812 acute stroke codes, 805 (28.6%) were excluded, because no application was used or no clinical data were available, leaving 2007 patients included in the analyses. EXPOSURES: Applications with clinical observations filled in by EMS paramedics for each acute stroke code enabling reconstruction of the following 7 prediction scales: Los Angeles Motor Scale (LAMS); Rapid Arterial Occlusion Evaluation (RACE); Cincinnati Stroke Triage Assessment Tool; Prehospital Acute Stroke Severity (PASS); gaze-face-arm-speech-time; Field Assessment Stroke Triage for Emergency Destination; and gaze, facial asymmetry, level of consciousness, extinction/inattention. MAIN OUTCOMES AND MEASURES: Planned primary and secondary outcomes were sLAVO and feasibility rates (ie, the proportion of acute stroke codes for which the prehospital scale could be reconstructed). Predictive performance measures included accuracy, sensitivity, specificity, the Youden index, and predictive values. RESULTS: Of 2007 patients who received acute stroke codes (mean SD age, 71.1 14.9 years; 1021 50.9% male), 158 (7.9%) had sLAVO. Accuracy of the scales ranged from 0.79 to 0.89, with LAMS and RACE scales yielding the highest scores. Sensitivity of the scales ranged from 38% to 62%, and specificity from 80% to 93%. Scale feasibility rates ranged from 78% to 88%, with the highest rate for the PASS scale. CONCLUSIONS AND RELEVANCE: This study found that all 7 prediction scales had good accuracy, high specificity, and low sensitivity, with LAMS and RACE being the highest scoring scales. Feasibility rates ranged between 78% and 88% and should be taken into account before implementing a scale.
Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively ...oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Early blood biomarkers to diagnose acute stroke could drastically reduce treatment delays. We investigated whether circulating small non-coding RNAs can serve as biomarkers to distinguish between ...acute ischemic stroke (IS), intracerebral hemorrhage (ICH) and stroke mimics (SM). In an ongoing observational cohort study, we performed small RNA-sequencing in plasma obtained from a discovery cohort of 26 patients (9 IS, 8 ICH and 9 SM) presented to the emergency department within 6 h of symptom onset. We validated our results in an independent dataset of 20 IS patients and 20 healthy controls. ICH plasma had the highest abundance of ribosomal and tRNA-derived fragments, while microRNAs were most abundant in plasma of IS patients. Combinations of four to five tRNAs yielded diagnostic accuracies (areas under the receiver operating characteristics curve) up to 0.986 (ICH vs. IS and SM) in the discovery cohort. Validation of the IS and SM models in the independent dataset yielded diagnostic accuracies of 0.870 and 0.885 to distinguish IS from healthy controls. Thus, we identified tRNA-derived fragments as a promising novel class of biomarkers to distinguish between acute IS, ICH and SM, as well as healthy controls.
Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, ...including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host–pathogen interactions.
Tetracycline is a common pharmaceutical product that is used to treat infections caused by bacteria. However, the overuse of tetracycline (TC) has created a large amount of harmful residue to the ...environment, thus it is utmost necessary to remove the tetracycline residues in the aquatic environment. There are some conventional tetracycline removal methods, including adsorption, biological treatment, membrane filtration, oxidation, etc. Activated carbon derived from agricultural waste is considered a low-cost and efficient adsorbent for TC adsorption. The use of iron-rich materials also helps enhanced the adsorption capability. In this study, the adsorption process using the activated derived from rubber seed shell (RSSC) and modified with α-FeOOH was investigated. The optimized adsorption parameters were found as pH = 5, adsorbent dosage of 1 g L
−1
catalyst, and contact time of 30 minutes. α-FeOOH/RSSC with RSSC:Fe(NO
3
)
3
.9H
2
O = 10:10 (RSSCF10) exhibited the best adsorption performance of 28.94% treatment efficiency and adsorption capacity of 65 mg g
−1
. The fitting data of kinetic and isotherm proved that tetracycline adsorption mainly resulted from monolayer physical adsorption, and the maximum adsorption capacities of RSSCF10 was 280.753 mg g
−1
. These results confirmed that RSSCF10 was a highly efficient and cost-effective adsorbent for the removal of tetracycline.
G-protein signaling modulators (GPSMs) are a class of proteins involved in the regulation of G protein-coupled receptors, the most abundant family of cell-surface receptors that are crucial in the ...development of various tumors, including breast cancer. This study aims to identify the potential therapeutic and prognostic roles of GPSMs in breast cancer. Oncomine and UALCAN databases were queried to determine GPSM expression levels in breast cancer tissues compared to normal samples. Survival analysis was conducted to reveal the prognostic significance of GPSMs in individuals with breast cancer. Functional enrichment analysis was performed using cBioPortal and MetaCore platforms. Finally, the association between GPSMs and immune infiltration cells in breast cancer was identified using the TIMER server. The experimental results then showed that all GPSM family members were significantly differentially expressed in breast cancer according to Oncomine and UALCAN data. Their expression levels were also associated with advanced tumor stages, and GPSM2 was found to be related to worse distant metastasis-free survival in patients with breast cancer. Functional enrichment analysis indicated that GPSMs were largely involved in cell division and cell cycle pathways. Finally, GPSM3 expression was correlated with the infiltration of several immune cells. Members of the GPSM class were differentially expressed in breast cancer. In conclusion, expression of GPSM2 was linked with worse distant metastasis-free outcomes, and hence could potentially serve as a prognostic biomarker. Furthermore, GPSM3 has potential to be a possible target for immunotherapy for breast cancer.
BACKGROUND AND PURPOSE:High-serum glucose on admission is a predictor of poor outcome after stroke. We assessed the association between glucose concentrations and clinical outcomes in patients who ...underwent endovascular treatment.
METHODS:From the MR CLEAN Registry, we selected consecutive adult patients with a large vessel occlusion of the anterior circulation who underwent endovascular treatment and for whom admission glucose levels were available. We assessed the association between admission glucose and the modified Rankin Scale score at 90 days, symptomatic intracranial hemorrhage and successful reperfusion rates. Hyperglycemia was defined as admission glucose ≥7.8 mmol/L. We evaluated the association between glucose and modified Rankin Scale using multivariable ordinal logistic regression and assessed whether successful reperfusion (extended Thrombolysis in Cerebral Infarction 2b-3) modified this association.
RESULTS:Of 3637 patients in the MR CLEAN Registry, 2908 were included. Median admission glucose concentration was 6.8 mmol/L (interquartile range, 5.9–8.1) and 882 patients (30%) had hyperglycemia. Hyperglycemia on admission was associated with a shift toward worse functional outcome (median modified Rankin Scale score 4 versus 3; adjusted common odds ratio, 1.69 95% CI, 1.44–1.99), increased mortality (40% versus 23%; adjusted odds ratio, 1.95 95% CI, 1.60–2.38), and an increased risk of symptomatic intracranial hemorrhage (9% versus 5%; adjusted odds ratio, 1.94 95% CI, 1.41–2.66) compared with nonhyperglycemic patients. The association between admission glucose levels and poor outcome (modified Rankin Scale score 3–6) was J-shaped. Hyperglycemia was not associated with the rate of successful reperfusion nor did successful reperfusion modify the association between glucose and functional outcome.
CONCLUSIONS:Increased admission glucose is associated with poor functional outcome and an increased risk of symptomatic intracranial hemorrhage after endovascular treatment.
Aortic aneurysm is an uncommon but life-threatening cause of hemoptysis. Treatments include surgery and/or endovascular intervention, each with its own advantages and disadvantages. Endovascular ...intervention is associated with good early and medium-term outcomes.
We report three cases of hemoptysis due to ruptured thoracic aortic aneurysm who underwent endovascular intervention. In all three cases, endovascular grafts were placed in the descending thoracic aorta, the number of grafts used was 1, the average time to stop hemoptysis was 4 to 5 days, and the length of hospital stay was between 6 and 8 days. No intravascular fistula, renal failure, prolonged mechanical ventilation and other major cardiovascular events were reported.
Endovascular treatment for descending TAA has been demonstrated to be safe and effective, particularly in emergencies in which patients presented with life-threatening hemoptysis, due to its rapid access to the aorta. In our experience at a tertiary hospital in southern Vietnam, the procedural time for a thoracic endovascular aortic repair is relatively brief and can last between 15 and 30 min. Thus, endovascular treatment for ruptured TAA can substantially improve patient prognosis, reduce mortality and complications.
The implementation of endovascular intervention can help improve prognosis, reduce mortality and complications in patients with hemoptysis due to ruptured thoracic aortic aneurysm.
•Hemoptysis due to ruptured thoracic aneurysms is fatal.•Endovascular approach is a good option to treat this entity.•The sooner, the better is the main reason to implement this technique in tertiary hospitals.
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