TMEM158 functions as an oncogene and promotes lung adenocarcinoma progression through the PI3K/AKT pathway via interaction with TWIST1.

Lung adenocarcinoma (LUAD) is a common and deadly form of lung cancer, with high rates of metastasis and unsatisfactory clinical outcomes. Herein, we examined the influence of TMEM158 on the LUAD progression. A combination of bioinformatic analyses was used to assess the TMEM158 expression pattern, prognostic implications, and potential function in LUAD. The levels of TMEM158 and TWIST1 were evaluated in clinical samples from LUAD patients using Western blot analysis and qRT-PCR. To discover the function and underlying molecular pathways of TMEM158 in LUAD, we employed a combination of experimental approaches in vitro, such as flow cytometry analysis and colony formation, Co-IP, CCK-8, Transwell, and wound-healing assays. Elevated expression of TMEM158 in LUAD is associated with increased cancer aggressiveness and a poor prognosis. In vitro experiments demonstrated that high levels of TMEM158 promote cell proliferation, progression through the cell cycle, migration, and invasion while suppressing apoptosis. Knockdown of TMEM158 produced opposite effects. The underlying mechanism involves TMEM158 and TWIST1 directly interacting, stimulating the PI3K/AKT signaling pathway in LUAD cells. This investigation emphasizes the molecular functions of TMEM158 in LUAD progression and proposes targeting it as a promising treatment approach for managing LUAD.

DNMT1 methylation of LncRNA-ANRIL causes myocardial fibrosis pyroptosis by interfering with the NLRP3/Caspase-1 pathway.

Myocardial fibrosis is a common pathological manifestation that occurs in various cardiac diseases. The present investigation aims to reveal how DNMT1/lncRNA-ANRIL/NLRP3 influences fibrosis and cardiac fibroblast pyroptosis. Here, we used ISO to induce myocardial fibrosis in mice, and LPS and ATP to induce myocardial fibroblast pyroptosis. The results showed that DNMT1, Caspase-1, and NLRP3 expression were significantly increased in fibrotic murine myocardium and pyroptotic cardiac fibroblasts, whereas LncRNA-ANRIL expression was decreased. DNMT1 overexpression decreased the level of LncRNA-ANRIL while increasing the levels of NLRP3 and Caspase-1. Contrarily, silencing DNMT1 increased the LncRNA-ANRIL and decreased the levels of NLRP3 and Caspase-1. Silencing LncRNA-ANRIL increased the levels of NLRP3 and Caspase-1. The present findings suggest that DNMT1 can methylate LncRNA-ANRIL during the development of myocardial fibrosis and CFs cell scorching, resulting in low LncRNA-ANRIL expression, thereby influencing myocardial fibrosis and cardiac fibroblast pyroptosis.

MiR-21-3p triggers cardiac fibroblasts pyroptosis in diabetic cardiac fibrosis via inhibiting androgen receptor.

AIMS/HYPOTHESIS: MicroRNA-21 has been implicated in diabetic complication, including diabetic cardiomyopathy. However, there is limited information regarding the biological role of the miR-21 passenger strand (miR-21-3p) in diabetic cardiac fibrosis. The aim of this study was to investigate the role of miR-21-3p and its target androgen receptor in STZ-induced diabetic cardiac fibrosis. METHODS: The pathological changes and collagen depositions was analyzed by HE, Sirius Red staining and Masson's Trichrome Staining. MiR-21-3p, AR, NLRP3, caspase1 and collagen I expression were analyzed by western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, miR one step qRT-PCR, respectively. A luciferase reporter assay was used to verify the interaction between miR-21 and the 3' untranslated region (3'UTR) of AR. RESULTS: Our results indicated that miR-21-3p level was up-regulated, while AR was decreased in STZ-induced diabetic cardiac fibrosis tissues and cardiac fibroblast. High glucose triggers cardiac fibroblasts pyroptosis and collagen deposition. Gain-of-function and loss-of-function assays demonstrated that miR-21-3p mediated the crucial role in diabetic cardiac fibrosis. Our results show that miR-21-3p bound to the 3'UTR of AR post-transcriptionally repressed its expression. We also found AR, which regulates cardiac fibroblasts pyroptosis and collagen deposition through caspase1 signaling. CONCLUSIONS: /interpretation: Taken together, our study showed that miR-21-3p aggravates STZ-induced diabetic cardiac fibrosis through the caspase1 pathways by suppressing AR expression.

TIMP-1 and MMP-9 expressions in COPD patients complicated with spontaneous pneumothorax and their correlations with treatment outcomes.

OBJECTIVE: To study the expressions of TIMP-1 and MMP-9 in patients with chronic obstructive pulmonary disease (COPD) complicated with spontaneous pneumothorax, and their correlations with treatment outcomes. METHODS: A total of 80 COPD patients complicated with spontaneous pneumothorax treated in our hospital from December 2015 to December 2017. The serum expressions of TIMP-1 and MMP-9 in 80 COPD patients complicated with spontaneous pneumothorax (COPD group) and 52 healthy volunteers (control group) were detected by ELISA. The correlations of TIMP-1 and MMP-9 expressions with arterial blood gas parameters as well as scores of MRC breathlessness scale and St. George's Respiratory Questionnaire (SGRQ) were analyzed. RESULTS: The serum expressions of TIMP-1 and MMP-9 of COPD group were significantly higher than those of control group (P<0.05), but the two groups had similar MMP-9/TIMP-1 ratios (P>0.05). For COPD group, TIMP-1 expression, MMP-9 expression, MMP-9/TIMP-1, Sa(O2) and p(O2) were not correlated (P>0.05). TIMP-1 expression was significantly positively correlated with MRC scale and SGRQ scores (P<0.05). Sa(O2), p(O2) and MRC scale score of low MMP-9 expression, low TIMP-1 expression and low MMP-9/TIMP-1 group were significantly improved compared with those of high MMP-9 expression, high TIMP-1 expression and high MMP-9/TIMP-1 group (P<0.05). MMP-9 expression, TIMP-1 expression or MMP-9/TIMP-1 was not correlated with improvement of SGRQ score. Pulmonary function improvement (Sa(O2) improvement rate ≥5% and/or p(O2) improvement rate ≥10%) was correlated with serum MMP-9 expression, baseline Sa(O2) and p(O2). CONCLUSION: Increase of serum TIMP-1 and MMP-9 expressions in COPD patients was correlated with symptoms and scores of quality of life, and the expressions were also correlated with short-term treatment reactivity.

Lower Circulating Folate Induced by a Fidgetin Intronic Variant Is Associated With Reduced Congenital Heart Disease Susceptibility.

BACKGROUND: Folate deficiency is an independent risk factor for congenital heart disease (CHD); however, the maternal plasma folate level is paradoxically not a good diagnostic marker. Genome-wide surveys have identified variants of nonfolate metabolic genes associated with the plasma folate level, suggesting that these genetic polymorphisms are potential risk factors for CHD. METHODS: To examine the effects of folate concentration-related variations on CHD risk in the Han Chinese population, we performed 3 independent case-control studies including a total of 1489 patients with CHD and 1745 control subjects. The expression of the Fidgetin (FIGN) was detected in human cardiovascular and decidua tissue specimens with quantitative real-time polymerase chain reaction and Western blotting. The molecular mechanisms were investigated by luciferase reporter assays, surface plasmon resonance, and chromatin immunoprecipitation. FIGN-interacting proteins were confirmed by tandem affinity purification and coimmunoprecipitation. Proteasome activity and metabolite concentrations in the folate pathway were quantified with a commercial proteasome activity assay and immunoassays, respectively. RESULTS: The +94762G>C (rs2119289) variant in intron 4 of the FIGN gene was associated with significant reduction in CHD susceptibility (P=5.1×10-14 for the allele, P=8.5×10--13 for the genotype). Analysis of combined samples indicated that CHD risks in individuals carrying heterozygous (GC) or homozygous (CC) genotypes were reduced by 44% (odds ratio [OR]=0.56; 95% confidence interval [CI]=0.47-0.67) and 66% (OR=0.34; 95% CI=0.23-0.50), respectively, compared with those with the major GG genotype. Minor C allele carriers who had decreased plasma folate levels exhibited significantly increased FIGN expression because the transcription suppressor CREB1 did not bind the alternative promoter of FIGN isoform X3. Mechanistically, increased FIGN expression led to the accumulation of both reduced folate carrier 1 and dihydrofolate reductase via inhibition of their proteasomal degradation, which promoted folate absorption and metabolism. CONCLUSIONS: We report a previously undocumented finding that decreased circulating folate levels induced by increased folate transmembrane transport and utilization, as determined by the FIGN intronic variant, serves as a protective mechanism against CHD. Our results may explain why circulating folate levels do not have a good diagnostic value.

Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification.

Cardiac fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In recent years, despite the underlying mechanisms of cardiac fibrosis are still unknown, numerous studies suggest that epigenetic regulation of cardiac fibrosis. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix protein, a process the epigenetic machinery plays a pivotal role. Epigenetic modifications contain three main processes: DNA methylation, histone modifications, and noncoding RNAs. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of molecule mechanisms that target epigenetic regulators as a means of treating cardiac fibrosis.

DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis.

AIM AND OBJECTIVE: Regulation of microRNA gene expression by DNA methylation may represent a key mechanism to drive cardiac fibrosis progression. Cardiac fibroblast autophagy is the primary source of cardiac fibrosis, but the mechanisms underlying this process are incompletely understood. Here we found that DNMT3A suppression of the microRNA-200b (miR-200b) through pathway leads to cardiac fibroblast autophagy in cardiac fibrosis. METHODS: To understand the impact of DNMT3A on miR-200b at cardiac fibrosis, the rat cardiac fibrosis model was established via the abdominal aortic coarctation. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and cultured. The expression of DNMT3A, miR-200b, collagen I was measured by western blotting, immunohistochemistry and qRT-PCR. Gain- or loss-of-function approaches were used to manipulate DNMT3A and miR-200b. RESULTS: DNMT3A level was upregulated and negatively correlated with miR-200b expression in fibrosis tissues and cardiac fibroblast. We found that autophagy was activated by miR-200b inhibitor and inactivated by miR-200b mimic in the rat cardiac fibroblast. Knockdown of DNMT3A notably increased the expression of miR-200b. CONCLUSIONS: Taken together, these findings indicate that DNMT3A regulation of miR-200b controls cardiac fibroblast autophagy during cardiac fibrosis and provide a basis for the development of therapies for cardiac fibrosis.

MicroRNA-21 via Dysregulation of WW Domain-Containing Protein 1 Regulate Atrial Fibrosis in Atrial Fibrillation.

BACKGROUND: microRNAs (miRs) have been reported to regulate cell biological functions. To explore the underlying mechanism of miR-21 involvement in patients with atrial fibrosis and atrial fibrillation (AF). METHODS: In total, 49 patients (24 AF, sinus rhythm 25) aged 33-68 years old, including heart valve replacement surgery and cardiac catheterisation. The pathological changes and collagen depositions was analysed by Masson's Trichrome Staining. miR-21, TGF-ß1, Smad2, p-Smad2, WWP-1, collagen I and collagen III expression were analysed by Western blotting, qRT-PCR, miR one step qRT-PCR, respectively. Treatment human cardiac fibroblasts with TGF-ß1, qRT-PCR and Western blotting to find changes in miR-21, Smad2 and WWP-1 levels. Transfected human cardiac fibroblasts with miR-21 mimic and miR-21 inhibitor. Finally, cell proliferation ability was assessed by the MTT assay and flow cytometry. RESULTS: Compared to sinus rhythm (SR) group, the collagen volume fraction was significantly increased in AF patients. The levels of the TGF-ß1, collagen I and collagen III were significantly elevated in AF group. In AF patients, the expression of miR-21 was increased, while the expression of WWP-1 was decreased. Transfected cardiac fibroblasts with miR-21 mimic increased miR-21 expression and decreased WWP-1 expression, whereas miR-21 inhibitor causes the opposite effects. Additionally, we demonstrated that knockdown miR-21 targeted up-regulation of WWP-1 may suppress cardiac fibroblasts proliferation. CONCLUSION: These indicated that miR-21 inhibits cardiac fibroblasts proliferation by inactivating the TGF-ß1/Smad2 signaling pathway via up-regulation of WWP-1.

Noncoding RNA as regulators of cardiac fibrosis: current insight and the road ahead.

Cardiac fibrosis is an important pathological feature of cardiac remodeling in heart diseases. The molecular mechanisms of cardiac fibrosis are unknown. Genomic analyses estimated that many noncoding DNA regions generate noncoding RNAs (ncRNAs). ncRNAs have emerged as key molecular players in the regulation of gene expression in different biological processes. Recent studies have started to reveal the importance of ncRNAs in heart development and suggest also an involvement in cardiac fibrosis. These molecules are emerging as important regulators of cellular process. Here, we review particularly focuses on the involvement of two large families of ncRNAs, namely microRNAs (miRNAs) and long noncoding RNAs (LncRNAs) in the regulation of cardiac fibrosis. Furthermore, we review the functions and role of ncRNAs in cardiac biology and discuss these reports and the therapeutic potential of ncRNAs for cardiac fibrosis associated with fibroblast activation and proliferation.

Epigenetic factors MeCP2 and HDAC6 control α-tubulin acetylation in cardiac fibroblast proliferation and fibrosis.

AIM AND OBJECTIVE: Cardiac fibrosis is an important pathological feature of cardiac remodeling in heart diseases. Methyl-CpG-binding protein 2 (MeCP2) is a transcription inhibitor, and plays a key role in the fibrotic diseases. However, the precise role of MeCP2 in cardiac fibrosis remains unclear. α-tubulin plays an essential role in cell function, whereby the acetylation state of α-Tubulin dictates the efficiency of cell proliferation and differentiation. This study was undertaken to investigate that MeCP2 dynamics affect the acetylation state of α-tubulin in the cardiac fibrosis. METHODS: Forty adult male Sprague-Dawley (SD) rats were randomly divided into two groups, cardiac fibrosis was produced by common ISO. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and cultured. The expression of HDAC6, MeCP2, α-SMA, collagen I was measured by western blotting and qRT-PCR. siRNA of HDAC6 and MeCP2 effect the proliferation of cardiac fibroblasts, and affect the acetylation state of α-tubulin. RESULTS: We have found the acetylation state of α-tubulin in cardiac fibroblasts as well as cardiac tissue from a ISO-induced rat cardiac fibrosis model and observed a reduction in acetylated α-tubulin and an increase in the α-tubulin-specific deacetylase, histone deacetylase 6 (HDAC6). Furthermore, we have shown that treatment of cardiac fibroblasts with HDAC6 inhibitor Tubastatin A and HDAC6-siRNA can restore α-tubulin acetylation levels. In addition, treatment of cardiac fibroblasts with MeCP2-siRNA blocked cell proliferation. Knockdown of MeCP2 suppresses HDAC6 expression in activated cardiac fibroblasts but increases the acetylation of α-tubulin. CONCLUSIONS: We demonstrated that MeCP2 may negatively control the acetylation of α-tubulin through HDAC6 in cardiac fibroblast proliferation and fibrosis. This study indicated that MeCP2 could be a potentially new therapeutic option for cardiac fibrosis.

HDAC6 Promotes Cardiac Fibrosis Progression through Suppressing RASSF1A Expression.

OBJECTIVES: Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. HDAC6 is a transcriptional regulator of the histone deacetylase family, subfamily 2. Previous studies have shown that HDAC6 plays critical roles in transcription regulation and proliferation events. However, the precise mechanisms of how HDAC is associated with cardiac fibrosis progression have not yet been elucidated. METHODS: Fifty adult male Sprague-Dawley (SD) rats were randomly divided into two groups. Cardiac fibrosis was produced by common isoprenaline and cardiac fibroblasts were harvested from SD neonate rats and cultured. The expression of HDAC6, RASSF1A, α-SMA and collagen I were measured by Western blotting and qRT-PCR. Small interfering (si)RNA of HDAC6 affects the proliferation of cardiac fibroblasts and the regulation of RASSF1A/ERK1/2 signaling pathways. RESULTS: In this study, we found that mRNA and protein levels of HDAC6 were upregulated in cardiac fibrosis tissues and activated cardiac fibroblast cells. Inhibition of HDAC6 by siRNA or the inhibitor tubacin attenuated the TGF-ß1-induced myofibroblast markers. In contrast, HDAC6 knockdown using siRNA inhibited cardiac fibroblast cell proliferation. Furthermore, we demonstrated that knockdown of HDAC6 elevated RASSF1A expression in activated cardiac fibroblasts, and treatment of cardiac fibroblasts with the HDAC6 inhibitor tubacin also elevated RASSF1A expression. CONCLUSIONS: The results of this study suggest that a previously unknown mechanism of HDAC6 inactivation of RASSF1A controls cardiac fibroblast proliferation and fibrosis.

The significance of YKL-40 protein in liver fibrosis.

OBJECTIVE: The aims of this review are to describe the present knowledge about YKL-40 protein, discuss its relation to liver fibrosis, and to look ahead at future perspectives of YKL-40 research. INTRODUCTION: Liver fibrosis is characterized by excess collagen deposition, decreased extracellular matrix degradation and activation of hepatic stellate cells. Therefore, advancement in the identification of liver fibrosis biomarkers with diagnostic and prognostic values becomes an important tool for future molecular therapy. The molecular basis of YKL-40 in liver fibrosis is unknown. METHODS: A PubMed database search was performed for studies of YKL-40 in liver injury and fibrosis. RESULTS AND CONCLUSIONS: YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization, and tissue remodeling as a response to endothelial damage. Several studies demonstrate that elevated serum YKL-levels are independently associated with the presence of endothelial damage and even higher YKL-40 levels are documented in liver fibrosis. YKL-40 may play a key role in liver injury and fibrosis.

Functional variant in methionine synthase reductase intron-1 significantly increases the risk of congenital heart disease in the Han Chinese population.

BACKGROUND: Homocysteine is known to be an independent risk factor for congenital heart disease (CHD). Methionine synthase reductase (MTRR) is essential for the adequate remethylation of homocysteine, which is the dominant pathway for homocysteine removal during early embryonic development. METHODS AND RESULTS: Here, we report that the c.56+781 A>C (rs326119) variant of intron-1 of MTRR significantly increases the risk of CHD in the Han Chinese population. In 3 independent case-control studies involving a total of 2340 CHD patients and 2270 healthy control participants from different geographic areas, we observed that patients carrying the heterozygous AC and homozygous CC genotype had a 1.40-fold (odds ratio=1.40; P=2.32×10(-7)) and 1.84-fold (odds ratio=1.84; P=2.3×10(-11)) increased risk, respectively, of developing CHD than those carrying the wild-type AA genotype. Both in vivo quantitative real-time polymerase chain reaction analysis of MTRR mRNA in cardiac tissue samples from CHD patients and in vitro luciferase assays in transfected cells demonstrated that the c.56+781 C allele profoundly decreased MTRR transcription. Further analysis demonstrated that the c.56+781 C allele manifested reduced CCAAT/enhancer binding protein-α binding affinity. In addition, healthy individuals with the homozygous CC genotype had significantly elevated levels of plasma homocysteine compared with the wild-type AA carriers. CONCLUSIONS: We have demonstrated that the MTRR c.56+781 A>C variant is an important genetic marker for increased CHD risk because this variant results in functionally reduced MTRR expression at the transcriptional level. Our results accentuate the significance of functional single-nucleotide polymorphisms in noncoding regions of the homocysteine/folate metabolism pathway core genes for their potential contributions to the origin of CHD.

Application of double low-dose mode in left atrial-pulmonary venous computed tomography angiography.

This study adopted a 256-slice iCT scanner with the double low-dose mode in left atrial-pulmonary venous computed tomography angiography (CTA) and explored its effect on image quality. 120 patients were included and randomly classified into the Observation group and Control group. Patients in the Control group underwent routine left atrial CTA, while patients in the Observation group performed a double low-dose mode. Other scanning parameters were consistent in the two groups. The Full model-based iterative reconstruction (MBIR) technique was applied to fulfill image reconstruction in observation group. Continuous variables, ordered categorical variables were analyzed by statistical test. The CT values of left atrial in the Observation group were significantly higher than those in the Control group. The exposure doses (ED) and iodine intake were lower in the Observation group, as compared to the Control group. The left atrial-pulmonary venous CTA with the 256-slice iCT scanner in a double low-dose mode can reduce the ED of radiation and iodine contrast while providing high quality images. Comparatively, the ED in the Observation group was reduced by 13% compared with the control, and the iodine intake was reduced by approximately 33%.

IGFBP3 epigenetic promotion induced by METTL3 boosts cardiac fibroblast activation and fibrosis.

Cardiac fibrosis remains an unresolved problem in heart disease. Its etiology is directly caused by the activation and proliferation of cardiac fibroblasts (CFs). However, there is limited information regarding the biological role of cardiac fibroblasts in cardiac fibrosis. Herein, we screened out a gene, IGFBP3, whose expression significantly increased in TGF-ß1-stimulated human primary CFs by mining RNA-Seq data for differential and WGCNA. We verified the IGFBP3's expression in transverse aortic constriction (TAC) surgery, isoproterenol (ISO)-induced cardiac fibrosis models, and TGFß1-stimulated mouse primary CFs. We also found that the knockdown of IGFBP3 could inhibit the migration and proliferation ability of CFs. Furthermore, we found that aberrant N6-methyladenosine(m6A) mRNA modifications in the animal model and activated CFs may regulate the expression of IGFBP3 in developing cardiac fibrosis. Silencing METTL3 could downregulate the expression of IGFBP3 and inhibit the activation of CFs and the degree of cardiac fibrosis both in vitro and in vivo. Indeed, we also verified the expression of METTL3 and IGFBP3 in the atrial tissues of patients with atrial fibrillation (AF). Thus, METTL3 may regulate IGFBP3's expression and CFs activation via RNA epigenetic modifications, laying the foundation for a specific and novel therapeutic target in cardiac fibrosis.

Epigenetic control of LncRNA NEAT1 enables cardiac fibroblast pyroptosis and cardiac fibrosis.

Cardiac fibroblasts (CFs) drive extracellular matrix remodeling after inflammatory injury, leading to cardiac fibrosis and diastolic dysfunction. Recent studies described the role of epigenetics in cardiac fibrosis. Nevertheless, detailed reports on epigenetics regulating CFs pyroptosis and describing their implication in cardiac fibrosis are still unclear. Here, we found that DNMT3A reduces the expression of lncRNA Neat1 and promotes the NLRP3 axis leading to CFs pyroptosis, using cultured cells, animal models, and clinical samples to shed light on the underlying mechanism. We report that pyroptosis-related genes are increased explicitly in cardiac fibrosis tissue and LPS-treated CFs, while lncRNA Neat1 decreased. Mechanistically, we show that loss of DNMT3A or overexpression of lncRNA Neat1 in CFs after LPS treatment significantly enhances CFs pyroptosis and the production of pyroptosis-related markers in vitro. It has been demonstrated that DNMT3A can decrease lncRNA Neat1, promoting NLRP3 axis activation in CFs treated with LPS. In sum, this study is the first to identify that DNMT3A methylation decreases the expression of lncRNA Neat1 and promotes CFs pyroptosis and cardiac fibrosis, suggesting that DNMT3A and NEAT1 may function as an anti-fibrotic therapy target in cardiac fibrosis.

Evolution of tricuspid regurgitation after mitral valve surgery for patients with moderate-or-less functional tricuspid regurgitation.

OBJECTIVES: The purpose of this study was to evaluate the impact of moderate-or-less functional tricuspid regurgitation (TR) treatment on the clinical outcome of patients with mitral valve (MV) surgery. METHODS: From October 2001 to January 2005, 167 patients in our hospital with MV surgery and without organic tricuspid valve (TV) disease or pulmonary hypertension (PH) showed moderate-or-less functional TR preoperatively, and 41.9% of these patients were treated with TR (group T), compared with 58.1% untreated with TR (group no-T). According to tricuspid annulus dimension (TAD)/body surface area (BSA), these 167 patients were further divided into another 2 groups (A and B): group A (70 patients) represented TAD/BSA ≤ 21 mm/m2 with 32 patients from group T and 38 from group no-T, and group B (97 patients) represented TAD/BSA > 21 mm/m2 with 38 patients from group T and 59 patients from group no-T. There was no statistical difference in preoperative and operative variables between the 2 groups. Meanwhile, among the 167 patients with MV surgery, 157 patients were replaced with MV and 10 patients were repaired with MV, and De Vega technique was constantly used for TR treatment. All the results were estimated by multivariate analysis. RESULTS: The median follow-up time was 63 months (25th and 75th percentiles are 53 and 94 months, respectively); 30-day mortality was 3% (1.4% in group T versus 4.1% in group no-T; P = .31). Adjusted 5-year survival was 70.7% (66.6%-80.4%) with 85.3% (83.0%-93.4%) in group T and 64.7% (33.7%-58.3%) in group no-T, P = .001. Among the 70 patients with TAD/BSA ≤ 21 mm/m2, patients who received treatment of moderate-or-less TR and those who did not showed similar secondary TR grade at postoperative period (0.5 ± 0.6 in group T versus 0.9 ± 0.9 in group no-T; P = .2) and follow-up (1.3 ± 1.1 in group T versus 1.8 ± 1.1 in group no-T; P = .06). In subgroup B (TAD/BSA > 21 mm/m2), patients who received tricuspid valvoplasty manifested more significantly improved outcome than patients without functional TR at postoperative period (0.8 ± 0.8 in group T versus 1.6 ± 1.3 in group no-T; P = .03) and follow-up (2.0 ± 1.2 in group T versus 3.0 ± 1.1 in group no-T; P = .005). The multivariate analysis identified TAD/BSA > 21 mm/m2 and preoperative atrial fibrillation (AF) as the risk factors for lower survival at follow-up period. CONCLUSIONS: Patients with MV surgery have better midterm outcome when they receive either more aggressive and effective surgical treatment for functional TR or moderate-or-less TR preoperatively. Indexed TAD (TAD/BSA > 21 mm/m2) is a more reliable surgical guideline for the treatment of TR. Preoperative tricuspid annulus dilation and AF might be predictors of late lower survival.

Mechanism of Action of Zhi Gan Cao Decoction for Atrial Fibrillation and Myocardial Fibrosis in a Mouse Model of Atrial Fibrillation: A Network Pharmacology-Based Study.

Atrial fibrillation (AF), a commonly seen cardiac disease without optimal curative treatment option, is usually treated by traditional Chinese medicine in China. The Zhi-Gan-Cao decoction (ZGCD) is an alternative medicine for clinical use and has definitive effects. It remains to be defined regarding the specific components and related mechanisms of ZGCD for the treatment of AF. We determined the primary constituents and major targets of the herbs in ZGCD using the TCMSP, HERB, and BATMAN-TCM databases. The UniProt databank database amended and combined the prospective names to supply objective data and records. Every target connected to AF was generated using the GeneCards databank, Drugbank database, TTD, Disgenet database, and OMIM. After identifying possible common targets between ZGCD and AF, the interface network illustration "ZGCD component-AF-target" was created using Cytoscape. We obtained 175 constituents and 839 targets for seven herbal drug categories in the ZGCD and identified 1008 targets of AF. After merging and removing repetitions, 136 collective targets between the ZGCD and AF were removed using the Cytoscape system. These renowned targets were generated from 38 suitable components from among the 157 components. GO enhancement examination and KEGG enrichment analysis by Metascape identified the close connection between the critical target genes and 20 signaling pathways. Then, we injected isoproterenol subcutaneously into the mouse and gave gavage with roasted licorice soup. Two weeks later, mouse were processed and sampled for testing. The results of HE and Masson staining showed that ZGCD effectively alleviated the degree of myocardial fibrosis. As indicated by qRT-PCR and Western blotting, ZGCD significantly reduced COL1A1, COL1A2, COL3A1, and TGF-ß1 in myocardial fibrotic tissue to reduce myocardial fibrosis and treat AF by interfering with the expression of COL1A1, COL1A2, COL3A1, and TGF-ß1 in myocardial tissue. ZGCD may treat AF by lowering the degree of myocardial fibrosis.

Silencing of integrin subunit α3 inhibits the proliferation, invasion, migration and autophagy of esophageal squamous cell carcinoma cells.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that seriously affects global public health. The aim of the present study was to explore the role of integrin subunit α3 (ITGA3) in ESCC and investigate its detailed molecular mechanisms. Using reverse transcription-quantitative PCR (RT-qPCR) and western blotting, the mRNA and protein expression of ITGA3 in cell lines was detected. In addition, a series of cellular biological experiments, including Cell Counting Kit-8, wound-healing, Transwell and TUNEL assays, were used to evaluate proliferation, migration, invasion and apoptosis, respectively. Furthermore, western blotting was used to measure the expression of corresponding proteins. ITGA3 was found to be upregulated in ESCC cell lines (ECA109 and TE1). It was also found that ITGA3 silencing inhibited the proliferation, migration, invasion and autophagy of ECA109 and TE1 cells but promoted their apoptosis. In addition, ITGA3 silencing was found to inhibit the FAK/PI3K/AKT signaling pathway. In conclusion, ITGA3 knockdown suppressed cell proliferation, invasion, migration and autophagy in ECA109 and TE1 cells, suggesting that ITGA3 may be a potential therapeutic target for the treatment of ESCC.

The effect of telemedicine on secondary prevention of atherosclerotic cardiovascular disease: A systematic review and meta-analysis.

Aim: The purpose of this systematic review was to evaluate the efficiency of telemedicine on the secondary level of prevention of patients with arteriosclerotic cardiovascular disease (ASCVD), provide evidence for the application of telemedicine in secondary prevention and promote the development of telemedicine in secondary prevention. Methods: A computer-based search was conducted in MEDLINE, Embase, Pubmed, EBSCO, CINAHL, the Cochrane Library, and Web of Science. Randomized controlled trials regarding the effect of telemedicine on secondary prevention of ASCVD were included from inception to May, 2022. Meta-analysis was used to compare the results of the included studies by RevMan5.4 software. The Cochrane Collaboration bias risk tool was used to perform risk of bias assessment in this study. Outcomes included risk factors, physical activity and exercise, muscle function, exercise compliance, medication adherence, healthy diet, depression and anxiety, self-efficacy, knowledge score, economy, and safety endpoints. Subgroup analysis was carried out for different main intervention measures included in the literature. Results: A total of 32 randomized clinical studies (n = 10 997 participants) were included in the meta-analysis. Compared with usual secondary prevention (USP) group, participants in telemedicine of secondary prevention (TOSP) group showed significant improvement in some risk factors including BMI (MD -0.87, p = 0.002), SBP (MD -4.09, p = 0.007) and DBP (MD -2.91, p = 0.0002) when they use the telephone as the intervention. In physical activity and exercise, Patients in TOSP showed an improvement in VO2 Peak (mL⋅kg-1⋅min-1) (OR 1.58, p = 0.02), 6MWT (MD 21.41, p = 0.001), GSLTPA score (MD 2.89, p = 0.005). Effects on medication adherence, exercise compliance, muscle function, healthy diet, economy and self-efficacy were synthesized narratively. Patients in TOSP did not show a reduction in knowledge score, depression, anxiety and safety endpoints. Conclusion: There is a net benefit of secondary prevention supported by telemedicine (especially when using the telephone as an intervention) in patients with ASCVD in the terms of some risk factors, physical activity and exercise. There are still controversies in the improvement of medication adherence, exercise compliance, muscle function, healthy diet, knowledge score, self-efficacy and economy via telemedicine, which is worth exploring. Larger samples size and longer-term follow-ups are needed in future studies. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=330478], identifier [CRD42022330478].