Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in human aortic dissection.

BACKGROUND: Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. METHODS: This study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database. RESULTS: This study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. CONCLUSION: In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network.

Systemic Inflammatory Markers for Predicting Overall Survival in Patients with Osteosarcoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Inflammatory markers are associated with tumor genesis and progression, but their prognostic significance in osteosarcoma remains unclear. Therefore, we discussed the prognostic value of related inflammatory markers in osteosarcoma through a meta-analysis and systematic review. These inflammatory markers include C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), and Glasgow prognostic score (GPS). METHODS: The Chinese National Knowledge Infrastructure (CNKI), Wanfang, Chinese Scientific Journals (VIP), PubMed, Embase, and Cochrane libraries were searched. The design of meta-analysis was made based on the PICOS (population, intervention/exposure, control, outcomes, and study design) principles, and STATA 15.1 was used to analyze the data. The Newcastle-Ottawa scale (NOS) was used to assess the quality of included studies. Hazard ratios (HRs) for overall survival (OS) and disease-specific survival (DPS) were extracted for the investigation of the prognostic value of inflammatory markers. RESULTS: Twelve researches with 2162 osteosarcoma patients were included in total. The pooled results showed that elevated NLR, CRP, and GPS are all greatly related to shortening of OS among patients with osteosarcoma (HR = 1.68, P = 0.007, 95% CI: 1.15-2.45; HR = 1.96, P = 0.002, 95% CI: 1.28-3.00; HR = 2.54, P < 0.0001, 95% CI: 1.95-3.31, respectively), and CRP level is significantly associated with shortening of DPS among patients with osteosarcoma (HR = 2.76, 95% CI:2.01-3.80, P < 0.0001), additionally. However, the correlation between LMR or PLR and the prognosis of osteosarcoma is not statistically significant (HR = 0.60, 95% CI: 0.30-1.18, P = 0.138; HR = 1.13, 95% CI: 0.85-1.49, P = 0.405, respectively). The outcomes of subgroup analysis to NLR and CRP suggested that histology, ethnicity, metastasis, and sample size all have an impact on its prognosis of patients with osteosarcoma. CONCLUSION: Worsened prognosis may be related to high levels of NLR, CRP, and GPS before treatment rather than LMR or PLR, which can provide the basis for clinicians to judge the outcomes of prognosis. Trial Registration. PROSPERO (CRD42021249954), https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=249954.

LIPH promotes metastasis by enriching stem-like cells in triple-negative breast cancer.

Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple-negative breast cancer (TNBC) patients. The ratio and mammosphere-forming ability of CD44+/CD24- stem-like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag-based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44+ /CD24- stem-like cells and their mammosphere-forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation-related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial-mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH-silenced cells and LIPH-mediated modulation of tumour cell adhesion depended on integrin-related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up-regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.

Endovascular and open surgical repair of abdominal aortic aneurysms: A comparative analysis of western and Chinese studies.

Abdominal aortic aneurysms (AAA) are life-threatening serious conditions that require effective and quick management. Although it is generally acknowledged that patients with AAA obtain the greatest benefit from endovascular repair (EVAR) compared to open surgical repair (OSR), there are few comparisons between the surgical approaches in Western versus Chinese patients. We aimed to perform a meta-analysis of studies in which EVAR was compared with OSR in the management of abdominal aortic aneurysms. We searched the Western literature through PubMed, OVID and Web of Science from 1991 until December 2018 and the Chinese-language literature from 1998 until December 2018. We pooled the results in January 2019 based on standardized inclusion and exclusion criteria and analyzed them using a conventional meta-analysis. Forty-five English papers with 31,074 AAA patients and twenty-one Chinese studies with 1,405 patients were included in this study. Chinese subjects were more likely to undergo endovascular repair than Western subjects (44.5% versus 41.5%, P = 0.012). The 30-day post-discharge mortality rate in Western studies was significantly lower for EVAR than for OSR (odds ratio (OR) = 0.481, P < 0.001). However, there was no significant reduction in the 30-day mortality rate following EVAR compared to OSR (OR = 0.733, P = 0.425) for Chinese patients. In Western patients, the postoperative complication rate of respiratory system and cardiac system was lower in the EVAR group than in the OSR group (OR = 0.270, P < 0.001 and OR = 0.411, P < 0.001, respectively), nevertheless, for Chinese patients, limb ischaemia was more common (OR = 1.539, P = 0.049) in the EVAR group. Whether in Western patients with an eight-year follow-up period or Chinese patients with a maximum four-year follow-up period, there was no significant difference between the EVAR and OSR groups in the all-cause death rate (hazard ratio (HR) = 1.026, P = 0.483 and HR = 1.173, P = 0.247, respectively). Chinese patients were more likely to receive EVAR than OSR and the 30-day mortality was significantly lower for EVAR than for OSR in Western patients but not in Chinese patients. Endovascular repair can be applied to Chinese patients with a reasonable safety margin. Further work is needed to explore the causes of these treatment differences.

Identification of a chitosanase from the marine metagenome and its molecular improvement based on evolution data.

Chitooligosaccharides have important application value in the fields of food and agriculture. Chitosanase can degrade chitosan to obtain chitooligosaccharides. The marine metagenome contains many genes related to the degradation of chitosan. However, it is difficult to mine valuable genes from large gene resources. This study proposes a method to screen chitosanases directly from the marine metagenome. Chitosanase gene chis1754 was identified from the metagenome and heterologously expressed in Escherichia coli. The optimal temperature and pH of CHIS1754 were 55 °C and 5.5, respectively. A mutant, CHIS1754T, with 15 single point mutations designed based on molecular evolution data was also expressed in E. coli. The results indicated that the thermal stability of CHIS1754T was significantly improved, as the Tm showed an increase of ~ 7.63 °C. Additionally, the kcat/Km of CHIS1754T was 4.8-fold higher than that of the wild type. This research provides new theories and foundations for the excavation, modification, and industrial application of chitosanases. KEY POINTS: A chitosanase gene, chis1754, was firstly identified from marine metagenome. A multi-site mutant was designed to improve enzyme stability and activity. The kcat/Kmof the designed mutant was 4.8-fold higher than that of the wild type.

Serum amyloid a protein as a potential biomarker in predicting acute onset and association with in-hospital death in acute aortic dissection.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening disorder in vascular surgery with a high early mortality. Serum amyloid A (SAA) is a kind of acute-phase protein with a rapid diagnostic value in other diseases. However, the researches on the performance of SAA for the diagnosis of AAD is still lacking. This retrospective study aimed to evaluate the SAA levels and further explore its potential diagnostic role in AAD patients. METHODS: SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) in 63 controls and 87 AAD patients. Laboratory examinations were also performed. And relative clinical information was collected from participants included in this study. RESULTS: SAA levels were significantly higher in AAD patients than those in healthy controls. SAA levels were independently associated with the risk of AAD. There was a positive significant correlation between SAA and C reactive protein (R = 0.442, and P = 0.001). Based on receiver-operating characteristic (ROC) analysis, the area under the curve (AUC) of SAA for the diagnosis of AAD were 0.942 with optimal cut-off points of 0.427 mg/L. For in-hospital mortality, the AUC of SAA were 0.732 with optimal cut-off points of 0.500 mg/L. According to logistic regression analysis, higher SAA levels represent a higher risk of in-hospital mortality (OR = 1.25; 95%CI: 1.07-1.47; P = 0.005). CONCLUSION: Our findings demonstrated that SAA levels were significantly enhanced in AAD. SAA was closely correlated with inflammatory parameters and coagulation-related parameters in AAD. Furthermore, SAA could be a potential bio-marker for identifying AAD in the early diagnosis. Finally, SAA > 5.0 mg/L are independently related to AAD in-hospital mortality.

Safety of Stenting and Endarterectomy for Asymptomatic Carotid Artery Stenosis: A Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE/BACKGROUND: A meta-analysis of recently published randomised controlled trials (RCTs) was performed to evaluate the safety of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for asymptomatic carotid stenosis with average risk. METHODS: The MEDLINE, Embase, and Cochrane Library databases were systematically searched for RCTs that compared CAS with CEA for asymptomatic carotid stenosis. These publications reported clinical outcomes after revascularisation in patients with asymptomatic carotid stenosis during their primary intervention. Trials published in English were searched for on 31 May 2017. End points (composite of ipsilateral stroke, any stroke, major stroke, minor stroke, myocardial infarction [MI], and death during the post-procedural period) were extracted from the publications by two reviewers. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for peri-operative outcomes following CAS and CEA using a fixed effects model. RESULTS: Five studies involving 3901 patients (1585 with CEA; 2316 with CAS) were included in the meta-analysis. The risk of any stroke during the peri-procedural period was significantly lower in patients who underwent CEA than CAS (OR 0.53; 95% CI 0.29-0.96). The difference between CAS and CEA in the rate of stroke could be driven by minor stroke (OR 0.50; 95% CI 0.25-1.00). The risk of death, major stroke, ipsilateral stroke, and MI were not significantly different between the two interventions (peri-procedural death: OR 1.49 [95% CI 0.26-8.68]; peri-procedural major stroke: OR 0.69 [95% CI 0.20-2.35]; peri-procedural ipsilateral stroke: OR 0.63 [95% CI 0.27-1.47]; peri-procedural MI: OR 1.75 [95% CI 0.84-3.65]). No robust conclusion could be drawn regarding mid to long-term complications because of the heterogeneity of the reported data. The different outcomes precluded any further analysis being conducted. CONCLUSION: Among patients with asymptomatic carotid stenosis, stenting has a significantly higher rate of any peri-procedural stroke and peri-procedural minor stroke than CEA, and similar risk of peri-procedural major stroke, peri-procedural ipsilateral stroke, or MI.

Seasonal incidence of ruptured abdominal aortic aneurysm and the influence of atmospheric pressure: a systematic review and meta-analysis.

Ruptured abdominal aortic aneurysm (rAAA) is a life-threatening condition with a high mortality rate. Seasonal variations in the incidence of rAAA and the influence of atmospheric pressure have been studied throughout decades; however, the conclusions are contradictory. Therefore, we aimed to conduct a meta-analysis and systematic review of literature on seasonal variations in rAAA incidence and the influence of atmospheric pressure. Studies investigating seasonal variations in rAAA incidence and influence of atmospheric pressure were retrieved. For dichotomous data, we generated risk ratios (RRs) and 95% confidence intervals (CIs) for rAAA incidence compared among seasons. The studies were subdivided according to latitude, elevation, and climatic types, for subgroup comparisons. Studies reporting monthly incidence and seasonal mortality were further investigated. For continuous data, standardized mean differences (SMDs) and 95% CIs were generated for atmospheric pressure comparisons. Twenty-four eligible studies were included, comprising a total of 38,506 patients with rAAA. Pooled rAAA incidence was 25% in spring, 23% in summer, 26% in autumn, and 26% in winter. Pooled analysis demonstrated a statistically significant higher rAAA incidence in winter than in summer (RR 1.10, P = 0.04) and in autumn than in summer (RR 1.11, P < 0.00001). However, there was no statistically significant difference among other seasons. In the study of the influence of atmospheric pressure, no statistically significant difference was observed. In conclusion, our study revealed a higher incidence of rAAA in autumn and winter than in summer; however, atmospheric pressure was found to exert no influence.

The effect of ambient temperature on the onset of acute Stanford type B aortic dissection.

BACKGROUND: The aim of this work was to study the associations between weather conditions and the occurrence of type B acute aortic dissections (ABAD). PATIENTS AND METHODS: This study was a retrospective review of all ABAD cases between January 1st, 2006 and December 31st, 2015. Using a time-series design and distributed lag non-linear models (DLNM), we estimated the relative risk (RR) of ABAD presentation associated with mean daily temperatures, including cumulative RR for a 28-day period, and RR for individual daily lags through 28 days. RESULTS: A total of 213 patients were admitted with ABAD. A significant association was found between the daily maximal temperature and the number of hospital admissions for ABAD. The lower the maximal temperature, the higher the incidence of ABAD (P = 0.044). Furthermore, the onset of ABAD was higher in winter than in summer and autumn (P = 0.009 and P = 0.001). Based on a time-series analysis, this study showed that the associations between mean daily temperature and ABAD presentation were not monotonic. Compared to the centered temperature at 8°C, the cumulative 28-day (lag 0 to lag 27) RR was significantly elevated at - 20 °C and - 19 °C for ABAD (RR = 1.39; 95%CI: 1.02, 1.98 and RR = 1.36; 95%CI: 1.02, 1.98). At the extreme low temperature (- 17.7 °C) in Shenyang, the cumulative 14-day (lag 0 to 13 day) and 21-day (lag 0 to 20 day) RR were remarkably increased for ABAD (RRlag14-day = 1.34; 95%CI: 1.08, 1.40 and RRlag21-day = 1.06; 95%CI: 1.06, 1.23). For the extreme high temperature, however, no particular finding was detected regarding acute and prolonged effects on ABAD. CONCLUSIONS: In general, low ambient temperature was significantly associated with ABAD presentations in comparison with high temperature. The effects of cold were delayed by two weeks and persisted for a few days.

[Comparative study in clinical features and managements of aortic dissection between Chinese and Caucasians].

OBJECTIVE: To explore differences in the clinical characteristics, treatment methods and progness of Chinese (Han) and Western populations (Caucasia) aortic dissection (aortic dissection, AD) patients. METHODS: According to the requirements of systematic review, We searched MEDLINE (1980-2014), Emabse (1980-2014), CBM (1980-2014) and CNKI (1980-2014) database overall, the meta-analyses were performed through STATA 12.0. RESULTS: A total of 6 697 Stanford A AD and 3 381 Stanford B AD Caucasian patients and 850 Standford A AD and 4 745 Stanford B AD Chinese Han patients were deemed eligible. It showed that average age of Han patients was lower, the proportion of Han group was 84.5%, while Cuacasian group was 66.9%, the differences were statistically significant (χ² = 365.37, P < 0.01). Han patients with history of smoking and that of coronarty heart diseases accounted for 53.0%, 13.8% separately, which were higher than those of Caucasian group, the differences were also statistically significant (χ² = 264.23, 68.417, P < 0.01).Besides these,the proportions of Han Stanford B AD patients who had hypertension, diabetes were also statistically significant higher than Caucasian group (χ² = 264.23, 68.417, P < 0.01). The Chinese group was more likely to appear nervous system and heart damages before surgery while the Caucasian group mostly appeared kidney and peripheral vascular damages. In the choice of treatment, the number of open surgery patients was significantly higher than that in Caucasian group. Domestic acute AD patients were more likely to accept TEVAR. The 30-day mortality of Chinese Han group in Stanford B was 2.4%, while Caucasians' mortality was 11.2%, the differences were statistically significant (χ² = 142.96, P < 0.01). CONCLUSIONS: The incidence of Chinese AD patients who are younger with more basic diseases has been increasing gradually, Although the 30-day mortality and complications rates of Chinese patients accepting early surgery intervention are lower than Caucasians, due to the less available data, large sample researches and further long-term follow-up will be needed.

[A comparative study on medium-long term results of conventional and eversion endarterectomy in management of carotid artery stenosis: a meta-analysis].

OBJECTIVE: To evaluate the medium-long term effectiveness of eversion (eCEA) and conventional (cCEA) carotid endarterectomy on carotid artery stenosis. METHODS: We searched MEDLINE (1970-2012.12), Ovid (1970-2012), CBM (1970-2012.12) and CNKI (1970-2012.12) database. Relevant journals and dissertation were also hand searched. Study selection and assessment, data collection and analyses were undertaken by two reviewers independently according to the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses were performed through software STATA 11.2. RESULTS: A total of 21 studies were deemed eligible (8 617 eCEA and 7 830 cCEA procedures), six of which were randomized and 14 non-randomized. Base on 15 121 patients underwent carotid artery stenosis including 16 447 cases, eCEA was association with a shorter mean operation time (WMD -85.00 min, P < 0.001), internal carotid artery clamp time (WMD -3.9 min, P < 0.01) and less shunt usage (OR = 0.20, P < 0.01). Furthermore, eCEA was associated with significant reduction in 30-day mortality (OR = 0.59, P = 0.013), perioperative stroke (OR = 0.63, P = 0.044), residual restenosis (OR = 0.51, P = 0.019) and carotid artery occlusion (OR = 0.44, P = 0.001). Although eCEA did not reduce medium-long term all-caused mortality (OR = 0.81, P = 0.143) during follow-up time, eCEA presented with a significant reduction in late residual restenosis (OR = 0.34, P < 0.01) and carotid artery occlusion (OR = 0.30, P < 0.01). A sub-analysis was performed on studies directly comparing eCEA with patch CEA (CEA+P), eCEA replicated the finding on perioperative stroke, 30-day mortality, and stroke-related death within short term and late residual restenosis. Concerning outcomes of RCT, eCEA presents with a significant reduction in the residual restenosis (OR = 0.43, 95%CI: 0.27, 0.69, P < 0.01) and carotid artery occlusion (OR = 0.11, 95%CI: 0.02, 0.62, P = 0.012) during following-up time. CONCLUSIONS: Eversion CEA compared to conventional CEA may be associated with a short operation time and a short block time. eCEA appears to be associated with better 30-day mortality and stroke outcome than cCEA. Eversion CEA may be more effective for long-term prevention of restenosis, however, in the long term, it is not associated with a reduction in all-cause mortality.

Investigating hybrid nanoparticles for drug delivery in multi-stenosed catheterized arteries under magnetic field effects.

This groundbreaking study pioneers the exploration of the therapeutic implications of a constant magnetic field simultaneously with hybrid nanoparticles on blood flow within a tapered artery, characterized by multiple stenosis along its exterior walls and a central thrombus, employing three-dimensional bio-fluid simulations. In addition, a magnetized catheter is inserted into the thrombus to increase the therapeutic potential of this novel method. The flow condition under consideration has applications in targeted medication distribution, improved medical device design, and improved diagnostics, as well as in advancing healthcare and biomedical engineering. Our investigation primarily aims to optimize blood flow efficiency, encompassing key parameters like pressure, velocity, and heat fluctuations influenced by diverse geometric constraints within the stenotic artery. Precise solutions are obtained through the finite element method (FEM) coupled with advanced bio-fluid dynamics (BFD) software. Hybrid nanoparticles and magnetic fields impacted pressure and velocity, notably reducing pressure within the stenosis. Convective heat flux remained uniform, while temperature profiles showed consistent inlet rise and gradual decline with transient variations. This approach promotes fluid flow, and convection within stenosed arteries, enhances heat transport, evacuates heat from stenotic regions, and improves heat dispersion to surrounding tissues. These findings hold promise for targeted therapies, benefiting patients with vascular disorders, and advancing our understanding of complex bio-fluid dynamics.

Body mass index and the risk of abdominal aortic aneurysm presence and postoperative mortality: a systematic review and dose-response meta-analysis.

BACKGROUND: The clinical data regarding the relationships between BMI and abdominal aortic aneurysm (AAA) are inconsistent, especially for the obese and overweight patients. The aims of this study were to determine whether obesity is associated with the presence of AAA and to investigate the quantitative relationship between BMI and the risk of AAA presence and postoperative mortality. MATERIALS AND METHODS: PubMed, Web of Science, and Embase databases were used to search for pertinent studies updated to December 2023. The pooled relative risk (RR) with 95% CI was estimated by conventional meta-analysis based on random effects model. Dose-response meta-analyses using robust-error meta-regression (REMR) model were conducted to quantify the associations between BMI and AAA outcome variables. Subgroup analysis, sensitivity analysis, and publication bias analysis were performed according to the characteristics of participants. RESULTS: Eighteen studies were included in our study. The meta-analysis showed a higher prevalence of AAA with a RR of 1.07 in patients with obesity. The dose-response meta-analysis revealed a nonlinear relationship between BMI and the risk of AAA presence. A 'U' shape curve reflecting the correlation between BMI and the risk of postoperative mortality in AAA patients was also uncovered, suggesting the 'safest' BMI interval (28.55, 31.05) with the minimal RR. CONCLUSIONS: Obesity is positively but nonlinearly correlated with the increased risk of AAA presence. BMI is related to AAA postoperative mortality in a 'U' shaped curve, with the lowest RR observed among patients suffering from overweight and obesity. These findings offer a preventive strategy for AAA morbidity and provide guidance for improving the prognosis in patients undergone AAA surgical repair.

Elucidating thoracic aortic dissection pathogenesis: The interplay of m1A-related gene expressions and miR-16-5p/YTHDC1 Axis in NLRP3-dependent pyroptosis.

The underlying molecular mechanisms of thoracic aortic dissection (TAD) remain incompletely understood. Recent insights into RNA methylation and microRNA-mediated gene regulation offer new avenues for exploring how these processes contribute to the pathophysiology of TAD, particularly through the modulation of pyroptosis and smooth muscle cell viability. This research aimed to elucidate the interplay of m1A-related gene expressions and miR-16-5p/YTHDC1 Axis in NLRP3-dependent pyroptosis, a mechanism implicated in the pathogenesis of TAD. We collected tissue samples from 28 human TAD patients and 8 healthy aortic group, as well as utilized a mouse model to replicate the disease. A combination of computational, in vitro, and in vivo methods was applied, including CIBERSORTx analysis, Pearson correlation, gene transfection using antagomiR-16-5p, siRNA, and several staining as well as cell culture techniques. Our analysis indicated two differentially expressed genes, ALKBH2 and YTHDC1. We found significant upregulation of has-miR-16-5p and downregulation of YTHDC1 at mRNA level in AD samples. Immune cell infiltration in TAD samples was examined using the CIBERSORTx database. We confirmed that YTHDC1 was a target of miR-16-5p, as evidenced by an inhibitory effect on luciferase activity. Inhibition of miR-16-5p enhanced SMC proliferation and promoted cell viability whilst downregulating NLRP3-pyroptosis. YTHDC1 expression was increased, and NLRP3-pyroptosis expressions were inhibited, suggesting miR-16-5p/YTHDC1 axis may involve the NLRP3-pyroptosis of the SMC. In vivo analyses confirmed the prevention of NLRP3-pyroptosis in middle layer of the thoracic aorta, implying that the miR-16-5p/YTHDC1 axis regulated SMC proliferation via NLRP3-pyroptosis signaling. Our findings underscored the anti-pyroptotic role of miR-16-5p/YTHDC1 axis in the pathogenesis of TAD, suggesting a potential therapeutic strategy via targeting YTHDC1 and suppressing miR-16-5p to inhibit NLRP3-dependent pyroptosis. Although further investigation is needed, these results relating to SMC proliferation are a significant step forward in understanding TAD.

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia-reperfusion injury: unfolding new epigenetic frontiers.

BACKGROUND: The management of myocardial ischemia-reperfusion injury (MIRI) presents continuous therapeutic challenges. NAD-dependent deacetylase Sirtuin 6 (Sirt6) plays distinct roles in various disease contexts and is hence investigated for potential therapeutic applications for MIRI. This study aimed to examine the impact of Sirt6-overexpressing exosomes derived from adipose stem cells (S-ASC-Exo) on MIRI, focusing on their influence on AIM2-pyroptosis and mitophagy processes. The sirtuin family of proteins, particularly Sirtuin 6 (Sirt6), play a pivotal role in these processes. This study aimed to explore the potential therapeutic effects of Sirt6-enriched exosomes derived from adipose stem cells (S-ASC-Exo) on regulating MIRI. RESULTS: Bioinformatic analysis revealed a significant downregulation of Sirt6 in MIRI subjected to control group, causing a consequential increase in mitophagy and pyroptosis regulator expressions. Therefore, our study revealed that Sirt6-enriched exosomes influenced the progression of MIRI through the regulation of target proteins AIM2 and GSDMD, associated with pyroptosis, and p62 and Beclin-1, related to mitophagy. The introduction of S-ASC-Exo inhibited AIM2-pyroptosis while enhancing mitophagy. Consequently, this led to a significant reduction of GSDMD cleavage and pyroptosis in endothelial cells, catalyzing a deceleration in the progression of atherosclerosis. Extensive in vivo and in vitro assays were performed to validate the expressions of these specific genes and proteins, which affirmed the dynamic modulation by Sirt6-enriched exosomes. Furthermore, treatment with S-ASC-Exo drastically ameliorated cardiac functions and limited infarct size, underlining their cardioprotective attributes. CONCLUSIONS: Our study underscores the potential therapeutic role of Sirt6-enriched exosomes in managing MIRI. We demonstrated their profound cardioprotective effect, evident in the enhanced cardiac function and attenuated tissue damage, through the strategic modulation of AIM2-pyroptosis and mitophagy. Given the intricate interplay between Sirt6 and the aforementioned processes, a comprehensive understanding of these pathways is essential to fully exploit the therapeutic potential of Sirt6. Altogether, our findings indicate the promise of Sirt6-enriched exosomes as a novel therapeutic strategy in treating ischemia-reperfusion injuries and cardiovascular diseases at large. Future research needs to underscore optimizing the balance of mitophagy during myocardial ischemia to avoid potential loss of normal myocytes.

Chemokines in patients with Alzheimer's disease: A meta-analysis.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly people. Many researches have reported that neuroinflammation is related to AD. Chemokines are a class of small cytokines that play important roles in cell migration and cell communication, which involved in neuroinflammation. Up to now there is no meta-analysis to explore the difference of chemokines between AD patients and healthy elderly individuals. Method: We searched PubMed, Web of science, Cochrane library, EMBASE and Scopus databases from inception to January 2022. Data were extracted by two independent reviewers, and the Review Manager 5.3 was used for the meta-analysis. Result: Thirty-two articles were included and analyzed. The total number of participants in the included study was 3,331. We found that the levels of CCL5 (SMD = 2.56, 95% CI: 1.91-3.21), CCL15 (SMD = 3.30, 95% CI: 1.48-5.13) and IP-10 (SMD = 3.88, 95% CI: 1.84-5.91) in the plasma of AD patients were higher than healthy people. MCP-1 protein (SMD = 0.67, 95% CI: 0.29-1.05) in the AD patients' CSF was higher than healthy controls. Conclusion: These results suggested that chemokines may play an important role in AD. These findings could provide evidences for the diagnosis and treatment of AD. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278736, identifier: CRD42021278736.

Clinical symbiosis of hybrid nanoparticles and induced magnetic field on heat and mass transfer in multiple stenosed artery with erratic thrombosis.

This article scrutinizes blood circulation through an artery having magnetized hybrid nanoparticles (silver and gold) with multiple stenoses at the outer walls and erratic thrombus of different radii at the center. In the realm of biomedical innovation, magnetized hybrid nanoparticles emerge as a captivating frontier. These nanoparticles, amalgamating diverse materials, exhibit magnetic properties that engender novel prospects for targeted drug delivery, medical imaging enhancement, and therapeutic interventions. The study was carried out employing modern bio-fluid dynamics (BFD) software. In this iterative procedure, a second-order finite difference approach is used to solve the governing equations with 0.005 tolerance. The experiment is performed on a blood conduit with mild stenosis assumptions, and expressions of temperature, resistance impedance to flow, velocity, wall shear stress, and pressure gradient are generated by employing related boundary conditions. No one has ever attempted to acquire the remedial impact of an induced magnetic field and hybrid nanoparticles on the bloodstream in a tapering artery containing multiple stenoses on the outside walls and multi-thrombus at the center using 3-D bio-fluid simulation. Furthermore, the study's findings are unique, and these computational discoveries were not previously published by any researcher. The findings suggest that hybrid nanoparticles can be used as medication carriers to reduce the impact of thrombosis and stenosis-induced resistance to blood flow or coagulation-related factors.

Efficacy and Safety of Five Broad-Spectrum Antiseizure Medications for Adjunctive Treatment of Refractory Epilepsy: A Systematic Review and Network Meta-analysis.

BACKGROUND: Overall, up to one-third of epilepsy patients have drug-resistant epilepsy. However, there was previously no meta-analysis to support the guidelines for broad-spectrum antiseizure medication selection for the adjunctive treatment of refractory epilepsy. In the present meta-analysis, we assessed the efficacy and safety of three second-generation broad-spectrum antiseizure medications, lamotrigine (LTG), levetiracetam (LEV), and topiramate (TPM), and two third-generation broad-spectrum antiseizure medications, perampanel (PER) and lacosamide (LCM), for the adjunctive treatment of refractory epilepsy. METHODS: We systematically searched PubMed, Embase, and CENTRAL from inception to July 15, 2022. The studies included in the meta-analysis were required to meet the following criteria: (1) be randomized, double-blind clinical trials; (2) include patients aged >2 years with a clinical diagnosis of drug-resistant epilepsy; (3) have at least 8 weeks for the treatment period excluding the titration phase; and (4) report the outcomes of seizure response, seizure freedom and the withdrawal rate due to treatment-emergent adverse effects. Data were extracted, and the risk of bias for each study was assessed by two authors independently using RoB2 tools. We performed the network meta-analysis for each outcome through a group of programs in the mvmeta and network packages in Stata. Relative odds ratios with 95% confidence intervals were calculated as the result of the analyses. The surface under the cumulative ranking curve (SUCRA) and mean ranks were used to rank these treatments. RESULTS: Forty-two randomized controlled trials (RCTs) (LTG-placebo: n = 6, LEV-placebo: n = 13, TPM-placebo: n = 9, PER-placebo: n = 6, LCM-placebo: n = 7, LEV-TPM: n = 1) with 10257 participants (LTG = 569, LEV = 1626, TPM = 701, PER = 1734, LCM = 1908, placebo = 3719) were included. Levetiracetam had subequal efficacy in 50 % seizure frequency reduction to TPM [odds ratio (OR) 1.00, 95% confidence interval (CI) 0.73-1.38], and LEV had a higher rate of ≥ 50% seizure frequency reduction than LCM (OR 1.49, 95% CI 1.11-2.01) and PER (OR 1.68, 95% CI 1.24-2.29). Levetiracetam was also related to a higher proportion of seizure freedom participants than TPM (OR 1.87, 95% CI 1.20-2.89), PER (OR 2.23, 95% CI 1.12-4.43), and LCM (OR 2.97, 95% CI 1.46-6.05). In addition, LEV was associated with a lower risk of experiencing at least one treatment-emergent adverse event (TEAE) than PER (OR 0.63, 95% CI 0.46-0.85) and TPM (OR 0.51, 95 % CI 0.36-0.72) and a lower proportion of patients experiencing TEAEs leading to discontinuation than PER (OR 0.51, 95% CI 0.27-0.97) and TPM (OR 0.50, 95 % CI 0.27-0.93). CONCLUSIONS: Third-generation drugs (PER and LCM) had no advantages in terms of efficacy and safety for adjunctive treatment of refractory epilepsy compared with several second-generation drugs (LEV and LTG). Levetiracetam was the priority choice for adjunctive treatment of refractory epilepsy. Perampanel and LCM had no advantages in terms of efficacy and safety among the five drugs. REGISTRATION: PROSPERO registration number, CRD42022344153; last edited on December 23, 2022.

The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection.

Aortic dissection (AD) develops pathological changes in the separation of the true and false aortic lumen, with high lethality. m6A methylation and oxidative stress have also been shown to be involved in the onset of AD. Through bioinformatics methods, three differentially expressed m6A regulators (YTHDC1, YTHDC2, and RBM15) were excavated from the GSE52093 dataset in the Gene Expression Omnibus (GEO) database, and functional enrichment analysis of the differentially expressed genes (DEGs) regulated by m6A regulators was performed. Then, the genes with oxidative stress-related functions among these genes were found. The protein interaction network of the oxidative stress-related genes and the competing endogenous RNA- (ceRNA-) miRNA-mRNA network were constructed. Among them, DHCR24, P4HB, and PDGFRA, which have m6A differences in AD samples, were selected as key genes. We also performed immune infiltration analysis, as well as cell-gene correlation analysis, on samples from the dataset. The results showed that YTHDC1 was positively correlated with macrophage M1 and negatively correlated with macrophage M2. Finally, we extracted AD and healthy aorta RNA and protein from human tissues that were taken from AD patients and patients who received heart transplants, performed quantitative real-time PCR (qRT-PCR) on YTHDC2 and RBM15, and performed qRT-PCR and western blot (WB) detection on YTHDC1 to verify their differences in AD. The mRNA and protein levels of YTHDC1 were consistent with the results of bioinformatics analysis and were downregulated in AD. Immunofluorescence (IF) was used to colocalize YTHDC1 and endothelial cell marker CD31. After knocking down YTHDC1 in human umbilical vein endothelial cells (HUVECs), reactive oxygen species (ROS) levels had a tendency to increase and the expression of peroxide dismutase SOD2 was decreased. This study provides assistance in discovering the role of m6A regulator YTHDC1 in AD. In particular, m6A modification participates in oxidative stress and jointly affects AD.

[Correlation of hemoglobin concentration with the diameter of abdominal aortic aneurysm and long-term patient survival].

OBJECTIVE: To assessed the relationships between hemoglobin concentration from the patients with abdominal aortic aneurysm (AAA) and its diameter as well as patients' long-term survival. METHODS: Between January 2002 to June 2012, 255 AAA patients were reviewed retrospectively. The outcomes were compared between 3 groups of different treatments (excluding 20 cases dead within 30 days). The procedures included open AAA repair (n=76), endovascular (EVAR) (n=62) and non-operated (n=97). The mean follow-up period was 63±42 months. The association of hemoglobin level with AAA diameter was assessed with multiple linear regression. Kaplan-Meier survival curves of anemic and non-anemic patient groups were compared by the log-rank method in 3 groups. Cox's proportional hazard regression mode was used to determine the effects of anemia on vital status after EVAR, open AAA repair or non-operation. RESULTS: A total of 88 (34.5%) of AAA patients had anemia. After adjustment for various risk factors, hemoglobin level was inversely correlated with maximal AAA diameter (ß=-0.152, P=0.017). During a long-term follow-up, the 5-year survival rates were 56%, 51% and 42% in anemic patients versus 94%, 90% and 80% in non-anemic ones. Survival was lower in anemic patients than those without anemia in 3 groups (P=0.005, 0.001, 0.025 by log-rank respectively). In three groups, according to multivariable Cox regression analysis, the hemoglobin levels were independently correlated with long-term mortality respectively after adjusting for various risk factors. The hemoglobin levels were correlated with death (HR: 0.923, 0.963, 0.963; P: 0.001, 0.002, 0.028; 95%CI: 0.8798-0.970, 0.941-0.986, 0.932-0.996). CONCLUSION: Hemoglobin concentration is independently associated with AAA diameter and reduced long-term survival after undergoing EVAR, open AAA repair and non-operation.