Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation.

Emerging from several decades of extensive research, key genetic elements and biochemical mechanisms implicated in neuroinflammation have been delineated, contributing substantially to our understanding of neurodegenerative diseases (NDDs). In this minireview, we discuss data predominantly from the past three years, highlighting the pivotal roles and mechanisms of the two principal cell types implicated in neuroinflammation. The review also underscores the extended process of peripheral inflammation that predates symptomatic onset, the critical influence of neuroinflammation, and their dynamic interplay in the pathogenesis of NDDs. Confronting these complex challenges, we introduce compelling evidence supporting the use of mesenchymal stem cell-based cell-free therapy. This therapeutic strategy includes the regulation of microglia and astrocytes, modulation of peripheral nerve cell inflammation, and targeted anti-inflammatory interventions specifically designed for NDDs, while also discussing engineering and safety considerations. This innovative therapeutic approach intricately modulates the immune system across the peripheral and nervous systems, with an emphasis on achieving superior penetration and targeted delivery. The insights offered by this review have significant implications for the better understanding and management of neuroinflammation.

Transcatheter tricuspid valve interventions: Current devices and clinical evidence.

The tricuspid valve is known as "the forgotten valve". Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease. TR is often late in the course of the disease when it becomes symptomatic, often being a marker of late-stage chronic heart failure with a poor prognosis and high mortality rate at long-term follow-up. Despite the clear correlation between TR and mortality, most TR patients are under-treated. Neither pharmacologic nor surgical treatment demonstrates a significant survival benefit. Isolated tricuspid valve surgery has the highest mortality rate of all valve surgeries. Therefore, there is an urgent clinical need for minimally invasive therapies to meet the needs of patients with TR. In recent years, a variety of transcatheter tricuspid valve interventions representing less invasive alternatives to surgery have shown promising results, which bring hope to patients with severe TR. The purpose of this review is to provide a complete and updated overview on current transcatheter tricuspid valve interventions and clinical evidence.

Sex-related differences in outcome of thoracic aortic surgery.

BACKGROUND: Sex-related dissimilarities' influence on outcomes following thoracic aortic surgery is poorly understood. Our aim is to examine sex-related disparities in patients undergoing thoracic aortic aneurysm (TAA). METHODS: A total of 455 cases undergoing thoracic aortic aneurysm (TAA) surgery were consecutively enrolled between December 2009 and December 2015 in a Chinese hospital. Primary outcomes, including overall mortality and related risk factors, were evaluated. Cox regression is utilized to recognize the independent risk factor of these consequences. RESULTS: Females, compared to males, had greater indexed aortic diameters and higher aortic transvalvular pressure differences. For the location of aortic aneurysms, females had a higher rate of aortic arch involvement, while males had a higher rate of root involvement. Females underwent less frequent complex proximal aortic operations compared with males (29.5% versus 46.9%; p < 0.001). Women and men both had a lower rate of aortic transvalvular pressure difference and LV volume index 7 days after thoracic aortic surgery. The overall mortality for the women's groups (11%) was suggestively greater compared to 4.9% for the men's groups (p = 0.026). Renal failure and aortic arch involvement were the main risk factors associated with males' survival, while maximum indexed aortic diameter and cross-clamp time were the risk factors associated with females' survival. CONCLUSIONS: The outcome after TAA surgery was less favorable in women with significantly increased overall mortality. It highlights the need to focus on implementing personalized surgery strategies and gender-specific guidelines in treating female patients following TAA surgery.

Pan-cancer Multi-omics Analysis Reveals HMGN1 as a Potential Prognostic and Immune Infiltration-associated Biomarker.

BACKGROUND: The High Mobility Group Nucleosomal Binding Domain 1 Gene (HMGN1) is crucial for epigenetic regulation. However, the specific function of HMGN1 in cancer development is unclear. METHODS: Raw data on HMGN1 expression were procured from Genotype-Tissue Expression (GTEx), the University of Alabama- Birmingham CANcer data analysis Portal (UALCAN), and The Cancer Genome Atlas (TCGA). Thereafter, the pan-cancer analysis was implemented to understand the HMGN1 expression patterns, prognostic value, and immunological features. Furthermore, the Gene Set Enrichment Analysis (GSEA) was executed via R language. In addition, the relationship between HMGN1 and the sensitivity of antitumor drugs was also determined. Finally, real-time PCR (RT-PCR) experiments were carried out. RESULTS: Pan-cancer analysis revealed that HMGN1 was upregulated in several solid tumors and was associated with pathological staging and poor prognosis. In addition, HMGN1 was found to be involved in regulating the tumor microenvironment. The GSEA enrichment analysis indicated that HMGN1 assisted in the regulation of oncogenic processes, especially metabolic and immune pathways. Furthermore, HMGN1 expression was linked to microsatellite instability (MSI) and tumor mutational burden (TMB) across diverse tumor types. RT-PCR assays indicated that HMGN1 was overexpressed in the gastric and breast cancer cell lines and tissues. CONCLUSION: This study highlighted the potential of HMGN1 as a biomarker for pan- - cancer analysis.

The pan-cancer multi-omics landscape of key genes of sialylation combined with RNA-sequencing validation.

BACKGROUND: Sialylation, the process of salivary acid glycan synthesis, plays a pivotal function in tumor growth, immune escape, tumor metastasis, and resistance to drugs. However, the association between sialylation and prognosis, tumor microenvironment (TME), and treatment response in a variety of cancers remains unclear. METHODS: A comprehensive survey of the expression profile, prognostic value, and genetic and epigenetic alterations of sialylation-related genes was performed in pan-cancer. Subsequently, the single-sample gene set enrichment analysis (ssGSEA) algorithm was used to compute sialylation pathway scores in pan-cancer. Correlations of sialylation pathway scores with clinical features, prognosis, and TME were evaluated using multiple algorithms. Finally, the efficacy of the sialylation pathway score in determining the effect of immunotherapy was evaluated. The expression of sialylation-related genes were verified by RNA-sequencing. RESULTS: Significant differences were observed in sialylation-related genes expression between tumors and adjacent normal tissues for most cancer types. Sialylation pathway scores differed according to the type of tumor, where the poor prognosis was correlated with high sialylation pathway scores in uveal melanoma (UVM) and pancreatic adenocarcinoma (PAAD). In addition, sialylation pathway scores were positively associated with the ImmuneScore, StromalScore and immune-related pathways. Moreover, the level of immune cells infiltration was higher in tumors with higher sialylation pathway scores. Finally, patients with high sialylation pathway scores were more sensitive to immunotherapy. CONCLUSION: Sialylation-related genes are essential in pan-cancer. The sialylation pathway score may be used as a biomarker in oncology patients.

Prognostic Value of Systemic Inflammation Response Index in Acute Type A Aortic Dissection.

BACKGROUND: The study aimed to evaluate the prognostic value of preoperative systemic inflammation response index (SIRI) for acute type A aortic dissection (ATAD) following open surgery. METHODS AND RESULTS: Totally, 410 ATAD patients underwent open surgery from 2019 to 2021 were enrolled in the study. Among the patients, the in-hospital mortality was 14.4%. Cox regression (95%CI 1.033-1.114p < 0.001) and receiver operating characteristic curve analysis (AUC = 0.718, p < 0.001) demonstrated the prognostic role of SIRI for in-hospital mortality after surgery. The optimal cut-off value of SIRI for in-hospital mortality was identified as 9.43 by maximally selected Log-Rank statistics. The patients were divided into high SIRI group (SIRI ≥ 9.43) and low SIRI group (SIRI < 9.43)) after the linear inverse relationship between SIRI and hazard ratio for in-hospital mortality was demonstrated by restricted cubic spline analysis (p = 0.0742). The Kaplan-Meier analysis illustrated that in-hospital mortality increased significantly in high SIRI group (p < 0.001). In addition, elevating SIRI was significantly associated with the incidence of coronary sinus tear (95%CI 1.020-4.475p = 0.044). Furthermore, the incidence rate of postoperative complications including renal failure (p < 0.001) and infection (p = 0.019) was higher in high SIRI group. CONCLUSION: The study indicated that preoperative SIRI could provide strong prognostic value for in-hospital mortality in ATAD patients following open surgery. Thus, SIRI was a promising biomarker for risk stratification and management prior to open surgery.

Outcomes of reoperation for total arch replacement combined with frozen elephant trunk after previous cardiovascular surgery.

BACKGROUND: Aortic arch replacement(TAR) combined with frozen elephant trunk (FET) technique is a high-risk operation after previous cardiovascular surgery. The aim of the study was to review our strategy and outcomes in this cohort. METHOD: Data were reviewed for patients who underwent TAR combined with FET after previous cardiovascular surgery from January 2010 to December 2020. The patients were divided into elective group and non-selective group. RESULTS: 63 eligible patients were divided into elective(n = 44) and non-elective(n = 19) groups. The interval between two operations was shorter in non-elective group than elective groups (P = 0.001). The indication for reoperation was different in two groups (P = 0.000), however, the type of reoperations has no differences. Cardiopulmonary bypass time was shorter in elective group than non-elective group (P = 0.000). The over-all 30-day mortality rate was 17.5%, and it was higher in non-elective group (P = 0.013). The 24h drainage increased in non-elective group (P = 0.001) as well as re-explore rate for bleeding (P = 0.022). Postoperative hospital stay prolonged in non-elective group (P = 0.002). However, rates of survival without further aortic events were 72.3 ± 7.1% in elective group, 72.9 ± 13.5% in non-elective group at 5 years, respectively (P = 0. 955). CONCLUSION: Reduced 30-day mortality and shortened post-operative hospital stay was observed in elective group, however, long-term survival rate without reintervention were not affected.

UBE2O ubiquitinates PTRF/CAVIN1 and inhibits the secretion of exosome-related PTRF/CAVIN1.

BACKGROUND: Exosomes are small vesicles released by cells, which have crucial functions in intercellular communication. Exosomes originated from cell membrane invagination and are released followed by multivesicular bodies (MVBs) fused with the cell membrane. It is known that Polymerase I and Transcript Release Factor (PTRF, also known as Caveolin-associated Protein-1, CAVIN1) plays an important role in caveolae formation and exosome secretion. And PTRF in exosomes has been identified as a potential biomarker in multiple malignancies such as glioma and renal cell carcinoma. However, the mechanisms of how to regulate the secretion of exosome-related PTRF remain unknown. METHODS: We performed exogenous and endogenous immunoprecipitation assays to investigate the interaction between ubiquitin-conjugating enzyme E2O (UBE2O) and PTRF. We identified UBE2O ubiquitinated PTRF using ubiquitination assays. Then, exosomes were isolated by ultracentrifugation and identified by transmission electronic microscopy, western blot and nanoparticle tracking analysis. The effect of UBE2O on the secretion of exosome-related PTRF was analyzed by western blot, and the effect of UBE2O on exosome secretion was evaluated by exosome markers and the total protein content of exosomes. RESULTS: Here, we showed that UBE2O interacts with PTRF directly and ubiquitinates PTRF. Functionally, we found that UBE2O inhibited the effects of PTRF on exosome secretion via decreasing caveolae formation. Importantly, UBE2O decreased exosome secretion, resulting in downregulating PTRF secretion via exosomes. Our study also identified Serum Deprivation Protein Response (SDPR, also known as Caveolin-associated Protein-2, CAVIN2) interacted with both UBE2O and PTRF. Furthermore, we found that SDPR promotes PTRF expression in exosomes. Interestingly, even in the presence of SDPR, UBE2O still inhibited the secretion of exosome-related PTRF. CONCLUSIONS: Our study demonstrated that UBE2O downregulated exosome release and controlled the secretion of exosome-related PTRF through ubiquitinating PTRF. Since exosomes play an important role in malignant tumor growth and PTRF included in exosomes is a biomarker for several malignant tumors, increasing UBE2O expression in cells has the potential to be developed as a novel approach for cancer treatment. Video Abstract.

An Analysis of Total Arch Re-Replacement After Proximal Aortic Surgery.

BACKGROUND: After proximal aortic surgery, total arch replacement (TAR) may again be needed because of recurrent dissection or aneurysm. This paper analyzed the relevant data of this technology with hopes of improving cognition and treatment. METHODS: There were a total of 60 eligible cases of secondary TAR after proximal aortic surgery in our center from 2010 to 2020. The primary surgical procedures included aortic valve replacement (AVR), ascending aortic replacement, Bentall, hemi-arch replacement, and thoracic endovascular aortic repair (TEVAR). The data were analyzed using the IBM SPSS Statistics 23.0 for Windows™ and presented as the mean ± standard deviations and direct frequencies, as appropriate. RESULTS: The interval between two operations was 44.8±53.6 months, 24 cases (40%) underwent emergency operation, the recurrence of type A dissection included 51 cases, accounting for 85% of the causes of total arch re-replacement. In the second surgical procedures, the ascending + TAR + stented elephant trunk (SET) implantation accounted for 75.0%. The overall surgical success rate was 98.3%. Postoperative respiratory complications were the most common, including infection, pneumothorax and hemothorax in 21 cases (35.6%). The second most common complication was acute kidney injury (AKI) in six cases (10.2%), and neurological complications took place in three cases (5.1%). The 30-day mortality rate was 15.3% and the 1-, 3- and 5-year survival rates were 96.0%, 84.0%, and 76.0%, respectively. CONCLUSIONS: The recurrence of dissection is the main cause of TAR after proximal aortic surgery, followed by aneurysm and the resurgical criteria for aneurysm needs to be unified. In addition to TAR, SET also is widely used. Despite high early mortality, its long-term prognosis is acceptable.

A hybrid hydrogel encapsulating human umbilical cord mesenchymal stem cells enhances diabetic wound healing.

BACKGROUND: Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy, but the development of hydrogel with suitable properties remains a great challenge. Thus, our study was conducted to combine an optimized hydrogel with stem cell to improve complex diabetic wound treatment. METHODS: This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound. RESULTS: We explored the relationship between mechanical stiffness and cell proliferation and differentiation potency, and found 10% GelMA hydrogel with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1ß, promoted vascular regeneration and collagen deposition after treatment of hUMSCs. CONCLUSIONS: The optimized hydrogel encapsulating hUMSCs improved diabetic wound healing, and has a broad implication for the treatment of diabetic complication. Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy. This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound. Hydrogel of 10% GelMA with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1ß, promoted vascular regeneration and collagen deposition after treatment of hUMSCs. The study supplies an alternative treatment for diabetic complication. Hydrogel-hUMSCs combined treatment accelerates wound closure in diabetic mice. A. Representative images of wounds during 21-day in vivo experiments. B. Quantification of wound closure rate (%) over 21-day period. C. HE staining of wounds at days 7, 14 and 21. The bar corresponds to 200 µm.

Prognostic Value of Modified Model for End-Stage Liver Disease Score in Patients Undergoing Isolated Tricuspid Valve Replacement.

Objective: Though the prognostic value of the model for end-stage liver disease (MELD) score in tricuspid surgery was confirmed, the unstable international normalized ratio (INR) may affect the evaluation effectiveness of the MELD score for isolated tricuspid valve replacement (ITVR). The aim of the study was to assess the prognostic value of modified MELD for ITVR. Methods and Results: A total of 152 patients who underwent ITVR were evaluated. The adverse outcome was defined as in-hospital mortality after surgery. The receiver operating characteristic (ROC) curve analysis demonstrated that a modified MELD score with albumin replacing INR (MELD-albumin) score presented well prognostic value [area under the curve (AUC) = 0.731, p = 0.006] for in-hospital mortality. Through Cox regression and further interval validation, the MELD-albumin score was identified as an independent predictor for in-hospital mortality. The optimal cutoff value of MELD-albumin was identified as 8.58 through maximally selected log-rank statistics. In addition, restricted cubic spline analysis demonstrated the linear inverse relationship between MELD-albumin and hazard ratio (HR) for in-hospital mortality. Kaplan-Meier analysis illustrated that in-hospital mortality was increased significantly in the high MELD-albumin (MELD-albumin ≥8.58) group than in the low MELD-albumin group (MELD-albumin <8.58; p < 0.001). Furthermore, high MELD-albumin was associated with lower body mass index (BMI), the incidence of lower extremities edema and moderate drinking history, and the MELD-albumin score was correlated with the value of aspartate transaminase (AST), alanine transaminase (ALT), and albumin. Furthermore, the incidence of renal failure (p = 0.003) and pulmonary infection (p = 0.042) was increased significantly in the high MELD-albumin group. Conclusion: The MELD-albumin score could provide prognostic value for ITVR. In addition, the MELD-albumin score was useful in risk stratification and patient selection for patients with tricuspid regurgitation (TR) prior to ITVR.

KLF4 prevented angiotensin II-induced smooth muscle cell senescence by enhancing autophagic activity.

BACKGROUND: Vascular aging is an important risk factor for various cardiovascular diseases. Transcription factor krüppel-like factor 4 (KLF4) could regulate the phenotypic transformation of the vascular smooth muscle cell (VSMC) in the pathogenesis of aortic diseases. The present study aimed to explore the role and mechanism of KLF4 in angiotensin II (Ang II)-induced VSMC senescence. METHODS: The VSMC senescence mouse model was induced by sustained release of Ang II (1.0 µg/kg/min) for 4 weeks. The premature senescent VSMCs were induced by Ang II (0.1 µmol/L) for 72 h. Cellular senescence was measured by senescence-associated ß-galactosidase (SA-ß-gal) activity and p53/p16 expression. The autophagic activity was evaluated by autophagic flux and autophagic marker expression. RESULTS: The expression of KLF4 was extremely increased in abdominal aorta tissues after 1-week Ang II stimulation (p < .01) but began to decrease in later periods. Decreased expression of KLF4 was also detected in premature senescent VSMCs. Overexpression of KLF4 could enhance the antisenescence ability of VSMCs. Significantly decreased amounts of SA-ß-gal-positive cells and lower p53/p16 expression were detected in KLF4-overexpressing VSMCs (p < .01). Next, telomerase reverse transcriptase (TERT) was identified as a direct downstream target of KLF4 in VSMCs. Overexpression of KLF4 in VSMCs prevented the decreased expression of TERT under Ang II stimulation condition, which could in turn, contribute to the enhanced autophagic activity, and ultimately to the improved antisenescence ability of VSMCs. CONCLUSIONS: Our results demonstrated that overexpression of KLF4 prevented Ang II-induced VSMC senescence by promoting TERT-mediated autophagy. These findings provided novel potential targets for the prevention and therapy of vascular aging.

Effective Approach with Extra Desorption Time to Estimate the Gas Content of Deep-Buried Coalbed Methane Reservoirs: A Case Study from the Panji Deep Area in Huainan Coalfield, China.

In this study, 11 core coal samples were collected from deep-buried coalbed methane (CBM) reservoirs with burial depth intervals of 900-1500 m for gas estimation content by a direct method. In desorption experiments, the cumulative gas desorption data were recorded within 2 h in the field on the basis of the China National Standard method. For accuracy, two improved methods were proposed. The results show that the gas contents of deep-buried coal samples based on the China National Standard and mud methods are 3.58-9.89 m3/t (average of 6.03 m3/t) and 3.74-10.05 m3/t (average of 6.20 m3/t), respectively. The proposed Langmuir equation and logarithmic equation methods exhibited nonlinear relationships between the cumulative desorption volume and desorption time, which yield values of 6.33-13.34 m3/t (average of 9.36 m3/t) and 6.15-13.86 m3/t (average of 10.37 m3/t), respectively. In addition, the two proposed methods combine the raw data within 2 h by the China National Standard method and additional desorption points during extra time, which are helpful for the ability of the hypothetical methods to calculate the gas content. The Langmuir equation method is a relatively more accurate method to estimate the gas content in comparison with the proposed logarithmic method, which is based on the relative error and comparison plots of actual data and simulated results. From the perspective of numerical value, the Langmuir equation method gives values 1.06-3.39 times (average of 1.86 times) those of the China National Standard method. These analyses show that the proposed Langmuir equation method with extra desorption points is an effective method to determine the gas content of deep-buried CBM reservoirs.

Systemic immune-inflammation index predicted short-term outcomes in ATAD patients undergoing surgery.

OBJECTIVE: Systemic immune-inflammation index (SII) is a biomarker that reflect systemic inflammation. We aimed to assess the value of SII in prediction of short-term outcomes in acute type A aortic dissection (ATAD) patients undergoing surgery. METHOD: All patients underwent surgery for ATAD at our institution from 2018 to 2020 (n = 324) were retrospectively reviewed and divided into low SII (<1582.6 × 109 /L) and high SII (≥1582.6 × 109 /L) group according to optimal cut-off values defined by receiver operating characteristic curve. Cox regression and Kaplan-Meier analyses were performed to illustrate the correlation between SII and postoperative short-outcomes, including 30-day mortality and main complications after surgery. RESULTS: In total, 48 (14.8%) patients died in 30 days after ATAD surgery. And multivariable Cox analysis demonstrated that high preoperative SII was closely related with 30-day mortality (hazard ratio: 3.532, 95% confidence interval: 1.719-7.255, p = .001). Furthermore, Kaplan-Meier analysis illustrated that the short-term mortality rate increased significantly in high SII group (p < .001). In addition, the incidence of main postoperative complications including major adverse cardiovascular events (p = .001) and multiorgan failure (p = .002) were higher in high SII group. However, the length of intensive unit stay (p = .909) and hospital stay (p = .836) presented no difference in two groups. CONCLUSION: The study indicated that SII was an available biomarker to predict postoperative short-term prognosis, but not length of stay in intensive care unit and hospital in ATAD patients. And SII may be applied to risk stratification and patient selection in ATAD patients before surgery.

Methodology for Lost Gas Determination from Exploratory Coal Cores and Comparative Evaluation of the Accuracy of the Direct Method.

In the coal exploration of China, the commonly used direct method within 120 min has potential errors in lost gas calculation of deep coal seam for its complex geological conditions. The exploration of deep coal resources by drilling holes in Huainan of Eastern China offered an opportunity to starting research into developing a new method. A developed method with error analysis was constructed to estimate the lost gas using the total desorption process obtained from exploratory coal cores. The accuracy of the direct method was also evaluated comparatively. The result shows that the desorption curve of tested coal samples matches the fitted curve equation. Desorption temperature and the tectonic coal with associated pore characteristics significantly affect the variation of the adsorption characteristics and the estimation of lost gas. The direct method obviously underestimates the lost gas, and methodology using a new lost gas estimation procedure with additional residual gas allows for achieving relatively accurate results of the determination of gas content in coal seams. The calculated result of the new method is about 1.00-1.41 times that of the direct method. The error analysis of desorption results allowed us to determine the dependence between the time (retrieval time and desorption time) and determination method. The time used for desorption in the tank is allowed to extend to less than 400 min or more than 1000 min, which is very potentially important to accurately get the coalbed gas content for coring samples, especially deep exploratory cores for field application.

Dysregulated long non-coding RNAs involved in regulation of matrix degradation during type-B aortic dissection pathogenesis.

Thoracic aortic dissection (TAD) is a catastrophic disease with the rupture of aortic media resulted mainly from the degradation of extracellular matrix. With the deep study of long non-coding RNAs (lncRNAs) in cardiovascular diseases, the correlation between lncRNAs and the TAD pathogenesis is under revealed. In this study, we aimed to screen the differentially expressed lncRNAs involved in the regulation of matrix degradation during type-B aortic dissection (TBAD), whose pathogenesis is more similar to atherosclerosis. A total of 393 aberrantly expressed lncRNAs and 432 aberrantly expressed mRNAs were identified in the descending aortic samples from TBAD patients. Then, co-expression analysis was applied to analyze the correlation between the top five differentially expressed lncRNAs and aberrantly expressed mRNAs, so as to screen the lncRNAs involved in the regulation of matrix degradation. The results showed that two transcripts from lnc-TNFSF14 (lnc-TNFSF14-2, and lnc-TNFSF14-3) were negatively interacted with MMP14 and MMP19. Subsequently, quantitative real-time PCR assay confirmed that lnc-TNFSF14-2 were negatively correlated with MMP14 (rs = - 0.8180) and MMP19 (rs = - 0.8449), and lnc-TNFSF14-3 was also negatively correlated with MMP14 (rs = - 0.7098) and MMP19 (rs = - 0.7728) in descending aorta from TBAD patients (n = 20). Overall, our study found the aberrant lncRNAs expression profiles in TBAD, and identified lnc-TNFSF14 as a potential target regulating matrix degradation. The results also provided crucial clues for lncRNAs function research on TBAD development.

Curcumin protects BV2 cells against lipopolysaccharide-induced injury via adjusting the miR-362-3p/TLR4 axis.

Curcumin was demonstrated to be an active ingredient with anti-inflammatory effects. This research was to investigate the effects of curcumin. We found that curcumin promoted cell viability and suppressed cell apoptosis. Meanwhile, curcumin decreased the level of cleaved caspase-3 and the release of TNF-α, IL-1ß, IL-6, but increased IL-10 release in LPS-treated BV2 cells. miR-362-3p expression was upregulated by curcumin, while TLR4 expression was downregulated. Besides, we observed that the cytoprotective effects of curcumin were lost when miR-362-3p was silenced. TLR4 was a direct target gene of miR-362-3p. Moreover, miR-362-3p deletion attenuated the cytoprotective effects of curcumin by regulating TLR4 expression in LPS-induced BV2 cells. Furthermore, curcumin suppressed p-p65 expression via regulating miR-362-3p/TLR4 axis. We discovered that curcumin exhibited protective effects against LPS-triggered cell injury via modulating miR-362-3p/TLR4 axis through NF-κB pathway.

Impact of a Higher Body Mass Index on Prolonged Intubation in Patients Undergoing Surgery for Acute Thoracic Aortic Dissection.

BACKGROUND: In recent years, obese patients presenting with acute thoracic aortic dissection have not been uncommon and there are often pulmonary complications among them. Whether a higher body mass index (BMI) is associated with more pulmonary complications or even a higher mortality rate has yet to be determined. This study aimed to evaluate the effects of higher BMI on pulmonary complications and other surgical outcomes. METHODS: A total of 404 patients who underwent acute thoracic aortic dissection surgery were retrospectively studied. They were divided into three groups based on their BMI: normal weight (BMI 18.5 to <25 kg/m2, n=173), overweight (BMI 25 to <30 kg/m2, n=145) and obese (BMI ≥30 kg/m2, n=86). Clinical data were collected and analysed among groups. RESULTS: No statistical significance was detected among the groups for postoperative complications, in-hospital mortality and hospital or ICU stay, except for prolonged intubation, the proportion of which was highest in the obese group followed by the overweight and normal groups (40.7% vs 29% vs 11%, respectively; p<0.001). Furthermore, logistic regression analysis showed that postoperative renal failure (OR=16.984) and cardiopulmonary bypass time (OR=1.013) were independent risk factors for in-hospital mortality, while higher BMI (OR=7.148 for BMI ≥25 and 18.967 for BMI ≥30), transfused red blood cells (OR=1.004), and postoperative renal failure (OR=7.386) were independent risk factors for prolonged ventilation (p<0.05). CONCLUSION: Body mass index had no effect on in-hospital mortality but may be closely correlated with prolonged intubation for patients undergoing aortic dissection surgery. This finding suggests that these patients should receive more aggressive pulmonary management.

Serum exosomal miR-378 upregulation is associated with poor prognosis in non-small-cell lung cancer patients.

BACKGROUND: Deregulated circulating microRNAs (miRNAs) are potential biomarkers for the early detection and prognosis prediction of non-small-cell lung cancer (NSCLC). The aim of the present study was to investigate the expression pattern of serum exosomal miR-378 in NSCLC and its correlation with clinical variables. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect serum exosomal miR-378 levels in 103 patients with NSCLC and 60 control subjects. RESULTS: Our results showed that serum exosomal miR-378 was significantly overexpressed in NSCLC patients, and serum exosomal miR-378 upregulation was clearly associated with positive lymph node metastasis and advanced TNM stage. In addition, receiver operating characteristic (ROC) analysis demonstrated that combination of serum exosomal miR-378 expression and carcinoembryonic antigen (CEA) had a high discriminating power to differentiate NSCLC subjects from controls. Moreover, serum exosomal miR-378 levels in 73 NSCLC cases were significantly decreased after radiotherapy and could be used as an indicator of radiotherapeutic response in NSCLC. Furthermore, survival analyses revealed that patients with higher serum exosomal miR-378 expression had poor overall survival. Multivariate analysis showed that serum exosomal miR-378 expression was independently associated with overall survival. CONCLUSIONS: Collectively, serum exosomal miR-378 has strong potential as a promising non-invasive biomarker for screening and monitoring NSCLC.

Correction: Transition metal substituted sandwich-type polyoxometalates with a strong metal-C (imidazole) bond as anticancer agents.

Correction for 'Transition metal substituted sandwich-type polyoxometalates with a strong metal-C (imidazole) bond as anticancer agents' by Hongxia Zhao et al., Chem. Commun., 2019, 55, 1096-1099.