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BACKGROUND: Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. METHODS: Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. RESULTS: YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1's inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. CONCLUSIONS: This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.
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MAIN CONCLUSION: The decreased capacity of auxin-, CTK-, and BR-mediated cell division and cell enlargement pathways, combined with the enhanced capacity of GA and ETH-, JA-, ABA-, SA-mediated stress-resistant pathways were presumed to be the crucial reasons for the formation of spur-type 'Red Delicious' mutants. Vallee Spur', which exhibit short internodes and compact tree shape, is the fourth generation of the spur-type bud sport mutant of 'Red Delicious'. However, the underlying molecular mechanism of these properties remains unclear. Here, comparative phenotypic, full-length transcriptome and phytohormone analyses were performed between 'Red Delicious' (NSP) and 'Vallee Spur' (SP). The new shoot internode length of NSP was Ë 1.53-fold higher than that of the SP mutant. Cytological analysis showed that the stem cells of the SP mutant were smaller and more tightly arranged relative to the NSP. By Iso-Seq, a total of 1426 differentially expressed genes (DEGs) were detected, including 808 upregulated and 618 downregulated genes in new shoot apex with 2 leaves of the SP mutant. Gene expressions involved in auxin, cytokinin (CTK), and brassinosteroid (BR) signal transduction were mostly downregulated in the SP mutant, whereas those involved in gibberellin (GA), ethylene (ETH), jasmonate (JA), ABA, and salicylic acid (SA) signal transduction were mostly upregulated. The overall thermogram analysis of hormone levels in the shoot apex carrying two leaves detected by LC-MS/MS absolute quantification showed that the levels of IAA-Asp, IAA, iP7G, OPDA, and 6-deoxyCS were significantly upregulated in the SP mutant, while the remaining 28 hormones were significantly downregulated. It is speculated that the decreased capacity of auxin, CTK, and BR-mediated cell division and cell enlargement pathways is crucial for the formation of the SP mutant. GA and stress-resistant pathways of ETH, JA, ABA, and SA also play vital roles in stem elongation. These results highlight the involvement of phytohormones in the formation of stem elongation occurring in 'Red Delicious' spur-type bud sport mutants and provide information for exploring its biological mechanism.
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Malus , Malus/genética , Cromatografía Liquida , Espectrometría de Masas en Tándem , Reguladores del Crecimiento de las Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Citocininas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: Aortic stenosis is a common heart valvular disease whose pathological processes include an inflammatory reaction and lipid accumulation. However, its detailed pathogenesis is yet to be completely elucidated. Therefore, it is of great significance to further explore the molecular mechanisms of aortic stenosis. METHODS: Four datasets were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differently expressed genes (DEGs) were screened between control and aortic stenosis samples. Secondly, weighted gene co-expression network analysis (WGCNA) was performed to find the highly relevant gene modules. Enrichment analysis and protein-protein interaction (PPI) networking were also performed, then Cytoscape was used to identify hub genes. Finally, the six participants (3 control participants and 3 patients with aortic stenosis) were recruited at the Tianjin Chest Hospital. In order to verify the expression level of USP14, several molecular experiments were performed, including hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence technology, real time-quantitative polymerase chain reaction (RT-qPCR), and western blotting. RESULTS: A total of 9636 DEGs were found between the control and aortic stenosis samples. The DEGs were mainly enriched in the autophagy-animal, cellular lipid catabolic process, apoptosis, and glycoside metabolic process categories. Eleven hub genes were identified via four different algorithms. Following verification of the patient samples, Ubiquitin-specific protease 14 (USP14) was found to be displayed at higher levels in the aortic stenosis samples. CONCLUSION: USP14 might be involved in the occurrence and development of aortic stenosis, so it would be a molecular target for early diagnosis and specific treatment of aortic stenosis. There is a significant association between the high expression of USP14 and aortic stenosis, indicating that this gene may be a genetic risk factor for aortic stenosis.
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Estenosis de la Válvula Aórtica/diagnóstico , Biomarcadores/metabolismo , Ubiquitina Tiolesterasa/genética , Proteasas Ubiquitina-Específicas/genética , Estenosis de la Válvula Aórtica/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/genética , Humanos , Mapas de Interacción de Proteínas/genética , Ubiquitina/genética , Ubiquitina Tiolesterasa/aislamiento & purificación , Proteasas Ubiquitina-Específicas/aislamiento & purificaciónRESUMEN
MAIN CONCLUSION: DNA methylation of anthocyanin biosynthesis-related genes and MYB/bHLH transcription factors was associated with apple fruit skin color revealed by whole-genome bisulfite sequencing. DNA methylation is a common feature of epigenetic regulation and is associated with various biological processes. Anthocyanins are among the secondary metabolites that contribute to fruit colour, which is a key appearance and nutrition quality attribute of apple fruit. Although few studies reported that DNA methylation in the promoter of MYB transcription factor was associated with fruit skin color, there is a general lack of understanding of the dynamics of global and genic DNA methylation in apple fruit. Here, whole-genome bisulfite sequencing was carried out in fruit skin of apple (Malus domestica Borkh.) cv. 'Red Delicious' (G0) and its four-generation bud sport mutants, including 'Starking Red' (G1), 'Starkrimson' (G2), 'Campbell Redchief' (G3) and 'Vallee spur' (G4) at color break stage. Correlation and linear-regression analysis between DNA methylation level and anthocyanin content, as well as the transcription levels of genes related to anthocyanin biosynthesis were carried out. The results showed that the number of differentially methylated regions (DMRs) and differentially methylated genes (DMGs) was considerably increased from G1 to G4 versus the number observed in G0. The mCHH context was dominant in apple, but the levels of mCG and mCHG of DMGs were significantly higher than that of the mCHH. Genetic variation of bud sport mutants from 'Red Delicious' was associated with differential DNA methylation. Additionally, hypomethylation of mCG and mCHG contexts in flavonoid biosynthesis pathway genes (PAL, 4CL, CYP98A, PER, CCoAOMT, CHS, and F3'H), mCHG context in MYB10 at upstream, led to transcriptional activation and was conductive to anthocyanin accumulation. However, hypermethylation of mCG context in bHLH74 at upstream led to transcriptional inhibition, inhibiting anthocyanin accumulation.
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Antocianinas/biosíntesis , Metilación de ADN , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Malus/metabolismo , Epidermis de la Planta/metabolismo , Metilación de ADN/genética , Regulación de la Expresión Génica de las Plantas/genética , Genes de Plantas/genética , Estudio de Asociación del Genoma Completo , Malus/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Bud sport mutants of apple (Malus domestica Borkh.) trees with a highly blushed colouring pattern are mainly caused by the accumulation of anthocyanins in the fruit skin. Hormones are important factors modulating anthocyanin accumulation. However, a good understanding of the interplay between hormones and anthocyanin synthesis in apples, especially in mutants at the molecular level, remains elusive. Here, physiological and comparative transcriptome approaches were used to reveal the molecular basis of color pigmentation in the skin of 'Red Delicious' (G0) and its mutants, including 'Starking Red' (G1), 'Starkrimson' (G2), 'Campbell Redchief' (G3) and 'Vallee spur' (G4). RESULTS: Pigmentation in the skin gradually proliferated from G0 to G4. The anthocyanin content was higher in the mutants than in 'Red Delicious'. The activation of early phenylpropanoid biosynthesis genes, including ASP3, PAL, 4CL, PER, CHS, CYP98A and F3'H, was more responsible for anthocyanin accumulation in mutants at the color break stage. In addition, IAA and ABA had a positive regulatory effect on the synthesis of anthocyanins, while GA had the reverse effect. The down-regulation of AACT1, HMGS, HMGR, MVK, MVD2, IDI1 and FPPS2 involved in terpenoid biosynthesis influences anthocyanin accumulation by positively regulating transcripts of AUX1 and SAUR that contribute to the synthesis of IAA, GID2 to GA, PP2C and SnRK2 to ABA. Furthermore, MYB and bHLH members, which are highly correlated (r=0.882-0.980) with anthocyanin content, modulated anthocyanin accumulation by regulating the transcription of structural genes, including CHS and F3'H, involved in the flavonoid biosynthesis pathway. CONCLUSIONS: The present comprehensive transcriptome analyses contribute to the understanding of the the relationship between hormones and anthocyanin synthesis as well as the molecular mechanism involved in apple skin pigmentation.
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Antocianinas/metabolismo , Frutas/metabolismo , Malus/genética , Malus/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Antocianinas/genética , Flavonoides/genética , Flavonoides/metabolismo , Frutas/genética , Frutas/crecimiento & desarrollo , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Mutación , Pigmentación/genética , Reguladores del Crecimiento de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Terpenos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Both L-4F, one apolipoprotein A-1 mimetic peptide, and statins can reduce progression of atherosclerosis by different mechanisms. The combination of the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We postulated that combination of L-4F and simvastatin may stimulate cholesterol efflux and related proteins expressions to alleviate atherosclerosis. METHODS: Thirty male wild-type (W-T) C57 BL/6 mice and apo E(-/-) mice were divided into five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4F group and the combination of simvastatin and L-4F group. After 16 weeks, serum lipids, atherosclerotic lesion areas, cholesterol efflux and the expressions of related proteins including ABCA1, SR-BI, ABCG1, LXRα and PPARγ were evaluated. RESULTS: The aortic atherosclerotic lesion areas were reduced more significantly by combination of both drugs than single agent, and cholesterol efflux was promoted more in combination group than simvastatin and L-4F group. Besides, the combination group promoted expressions of cholesterol efflux related proteins. CONCLUSIONS: The combination of L-4F and simvastatin reduced atherosclerotic lesions, which stimulates cholesterol efflux by promoting the expressions of related proteins. In addition, these results help us further understand that the regression of the atherosclerosis would be assessed by reduction in LDL-C with increase of cholesterol efflux.
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Aterosclerosis/tratamiento farmacológico , Colesterol/metabolismo , Expresión Génica/efectos de los fármacos , Hipolipemiantes/farmacología , Péptidos/farmacología , Placa Aterosclerótica/tratamiento farmacológico , Simvastatina/farmacología , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Apolipoproteína A-I/química , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/patología , Transporte Biológico/efectos de los fármacos , LDL-Colesterol/sangre , Quimioterapia Combinada , Lipoproteínas/genética , Lipoproteínas/metabolismo , Receptores X del Hígado , Masculino , Ratones , Ratones Noqueados , Imitación Molecular , Receptores Nucleares Huérfanos/genética , Receptores Nucleares Huérfanos/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Receptores Depuradores de Clase B/genética , Receptores Depuradores de Clase B/metabolismoRESUMEN
A new indole-diterpenoid, penijanthine E (1), and a known analogue (2), were obtained from the PDB culture of the marine-derived fungus Penicillium citrinum ZSS-9. The absolute configuration of 1 was elucidated by calculated TDDFT ECD and DP4plus calculations. The absolute configuration of 2 was confirmed by single-crystal X-ray diffraction analysis and TDDFT ECD calculations. Compounds 1 and 2 showed antiviral activity against influenza A virus (IAV) of A/WSN/33(H1N1) and A/PR/8/34(H1N1) strains with IC50 values ranging from 12.6 to 46.8 µM.
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Diterpenos , Subtipo H1N1 del Virus de la Influenza A , Penicillium , Estructura Molecular , Penicillium/química , Diterpenos/química , Indoles/farmacología , Indoles/química , HongosRESUMEN
Background: Pulmonary artery hypertension (PAH) is a common complication of congenital heart disease (CHD) and is associated with worse outcomes and increased mortality. The Doppler echocardiography (DE) is a commonly used imaging tool for both diagnosis and follow-up examination of PAH. Here is to evaluate the diagnostic performance of DE combined with NTproBNP/BNP as screening strategy in PAH patients with CHD. Methods: A retrospective study in 64 patients with CHD has been carried out to compare estimate pulmonary artery systolic pressure (PASP) measured with DE to that measured with right heart catheterization (RHC). The Pearson correlation analyses were used to calculate the correlation coefficients between RHC and DE. The Bland-Altman analyses were carried out to assess the agreement between the two methods. ROC analyses were used to evaluate the diagnostic performance of DE, NTproBNP/BNP, and DE combined with NTproBNP/BNP. Results: Our data have demonstrated that a mild correlation (r = 0.4401, P < 0.01) was observed between PASP (78.1 ± 29.0 mmHg) measured during RHC and PASP (74.9 ± 19.7 mmHg) as estimated using DE. The Bland-Altman analysis demonstrated that the bias for DE PASP estimates was 3.2 mmHg with 95% limits of agreement ranging from -49.53 to 55.90 mmHg. The results of DE showed an AUC of 0.848 (95% CI = 0.666-1; P < 0.001), the sensitivity of which was 98.3% and the specificity was 77.8%. The AUC of NTproBNP/BNP for the identification of PAH was 0.804 (95% CI = 0.651-0.956; P < 0.001), the sensitivity of which was 81.4% and the specificity was 87.5%. The AUC of DE combined with NTproBNP/BNP was 0.857 (95% CI = 0.676-1; P < 0.001), of which sensitivity was 100% and specificity was 77.8%. The positive predictive value (PPV) and negative predictive value (NPV) were 96.6% and 100%, respectively. Conclusions: Our study shows that the Doppler echocardiography combined with NTproBNP/BNP has better diagnostic performance in pulmonary artery hypertension associated with congenital heart disease, especially when DE negative screening in PAH patients.
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Cardiopatías Congénitas , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Arteria Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Ecocardiografía Doppler/métodos , Cardiopatías Congénitas/complicacionesRESUMEN
OBJECTIVE: Atherosclerosis is characterized by the formation of fibrofatty plaques in the intima of arteries, resulting in thickening of the vessel wall and narrowing of the lumen. Chronic stress refers to individuals in a state of long-term chronic stress. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and chronic stress is unclear. METHOD: The atherosclerosis with chronic stress group data file was used. DEGs were screened and WGCNA was performed. Construction and analysis of PPI Network. Functional enrichment analysis, GSEA, gene expression heatmap, immune infiltration analysis and mRNA analysis were performed. CTD was used to find diseases most related to core genes. WB was performed. TargetScan was used to screen miRNAs of DEGs. RESULTS: 1708 DEGs were identified. According to GO analysis, they were mainly enriched in catabolic processes, organic acid metabolism processes, carboxylic acid metabolism processes. KEGG analysis showed that they were mainly enriched in metabolic pathways, fatty acid metabolism, pentose phosphate pathway, glycolysis / gluconeogenesis, fructose and mannose metabolism. Gene expression heatmap showed that the core genes (NDUFB11, NDUFS3) were lowly expressed in samples of those with atherosclerosis accompanied by chronic stress and highly expressed in the normal samples. NDUFB11 and NDUFS3 were associated with necrosis, hyperplasia, inflammation, renal disease, weight loss, memory impairment, and cognitive impairment. WB showed that the expression level of NDUFS3 in atherosclerosis and chronic stress was lower than that in control group. CONCLUSIONS: NDUFB11 and NDUFS3 are underexpressed in atherosclerosis and chronic stress; the lower NDUFB11 and NDUFS3 levels, the worse the prognosis.
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Aterosclerosis , Disfunción Cognitiva , MicroARNs , Humanos , Arterias , Fructosa , NADH Deshidrogenasa , Complejo I de Transporte de ElectrónRESUMEN
Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body's deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.
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Aterosclerosis , MicroARNs , Trombosis de la Vena , Humanos , Histidina , Trombosis de la Vena/genética , Arteria Pulmonar , Perfilación de la Expresión Génica , Aterosclerosis/genética , Biología Computacional , NADH Deshidrogenasa , Complejo I de Transporte de Electrón/genéticaRESUMEN
BACKGROUND: Circular RNAs (circRNAs) have attracted extensive attention as therapeutic targets in gastric cancer (GC). Circ_0003356 is known to be downregulated in GC tissues, but its cellular function and mechanisms remain undefined. AIM: To investigate the role of circ_0003356 in GC at the molecular and cellular level. METHODS: Circ_0003356, miR-668-3p, and SOCS3 expression were assessed via quantitative real time-polymerase chain reaction (qRT-PCR). Wound healing, EdU, CCK-8, flow cytometry and transwell assays were used to analyze the migration, proliferation, viability, apoptosis and invasion of GC cells. The subcellular localization of circ_0003356 was monitored using fluorescence in situ hybridization. The interaction of circ_0003356 with miR-668-3p was confirmed using RIP-qRT-PCR, RNA pull-down, and dual luciferase reporter assays. We observed protein levels of genes via western blot. We injected AGS cells into the upper back of mice and performed immunohistochemistry staining for examining E-cadherin, N-cadherin, Ki67, and SOCS3 expressions. TUNEL staining was performed for the assessment of apoptosis in mouse tumor tissues. RESULTS: Circ_0003356 and SOCS3 expression was downregulated in GC cells, whilst miR-668-3p was upregulated. Exogenous circ_0003356 expression and miR-668-3p silencing suppressed the migration, viability, proliferation, epithelial to mesenchy-mal transition (EMT) and invasion of GC cells and enhanced apoptosis. Circ_0003356 overexpression impaired tumor growth in xenograft mice. Targeting of miR-668-3p by circ_0003356 was confirmed through binding assays and SOCS3 was identified as a downstream target of miR-668-3p. The impacts of circ_0003356 on cell proliferation, apoptosis, migration, invasion and EMT were reversed by miR-668-3p up-regulation or SOCS3 down-regulation in GC cells. CONCLUSION: Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.
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OBJECTIVE: To investigate the impact of depression on clinical outcome of patients undergoing revascularization. METHODS: Self-rating depression scale (SDS) assessment was made before and after coronary artery bypass grafting (CABG, n = 345) and percutaneous coronary intervention (PCI, n = 308) procedure. Patients were divided into depression and non-depression group. All patients were followed up for 12 months after procedure for the occurrence of rehospitalization and major adverse cardiovascular events (MACE) including all-cause mortality, nonfatal myocardial infarction or target lesion revascularization. RESULTS: Depression was present in 40.9% (n = 141) of patients after CABG, which was significantly higher than before procedure (24.3%, P < 0.01). The MACE rate was significantly higher in patients with post-procedure depression [8.5% (12/141)] than in patients without depression [2.9% (6/204), P < 0.05] and the incidences of target lesion revascularization and rehospitalization were also significantly higher in depression patients than in non-depression patients during the 12 months follow-up (all P < 0.05). Depression was present in 36.4% (n = 112) of patients after PCI, which was significantly higher than that before procedure (28.6%, P < 0.05). The MACE rate [8.0% (9/112) vs. 2.0% (4/196)] and rehospitalization rate [12.5% (14/112) vs. 4.6% (9/196)] were significantly higher in depression patients than in patients without depression during the 12 months follow-up (P < 0.05). There was no significant difference on SDS score between the PCI and CABG before the procedure. However, after the procedure, the SDS score for patients undergoing CABG was significantly higher than in patients undergoing PCI (48.9 ± 9.8 vs. 45.7 ± 10.5 P = 0.01). The level of serum IL-6 was significantly higher in depression patients than in patients without depression (P < 0.05). CONCLUSION: Prevalence of depression is high in patients treated with revascularization procedures and is linked with poor post-procedure prognosis.
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Enfermedad Coronaria/psicología , Enfermedad Coronaria/terapia , Depresión/etiología , Anciano , Angioplastia Coronaria con Balón , Puente de Arteria Coronaria , Enfermedad Coronaria/diagnóstico , Estenosis Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Liriodendrin is a therapeutic constituent of sargentgloryvine stem which is a famous Chinese traditional medicine. Previous studies have suggested liriodendrin could inhibit different pathways to treat inflammation in lung and intestinal tract. But whether it can treat myocardial infarction (MI) is unknown. We investigated the protective effect of liriodendrin on acute MI in rats and explored the specific mechanisms to expand the use of this traditional Chinese medicine. METHODS: The rats were randomized into the sham group (sham operation), control group (ligation of the left anterior descending artery), and liriodendrin group. The liriodendrin group was intragastrically administered with a liriodendrin solution (100 mg/kg). The control group and the sham group were intragastrically administered with normal saline. Before all rats were euthanized, echocardiography was used to detect their cardiac function. Hematoxylin and eosin (HE) staining and the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method were performed. Further quantitative detection of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in tissues were also detected. Western Blot and real-time polymerase chain reaction (RT-PCR) were used to detect the apoptosis and nuclear factor kappa-B (NF-κB) pathway in tissues. H9C2 cells were used to detect the related mechanisms in vitro. RESULTS: Echocardiography showed that, compared to control group, the cardiac function of the liriodendrin group was significantly improved. histopathological staining of the control group showed that the myocardial tissue was severely damaged, and inflammatory cells were infiltrated. Compared to the control group, the apoptosis index of the liriodendrin group was significantly lower (P<0.05). Enzyme-linked immunosorbent assay (ELISA) results showed that the levels of IL-1ß and TNF-α in the control group were higher than those in the liriodendrin group (P<0.05). Meanwhile, apoptosis and the NF-κB pathway were inhibited after liriodendrin administration (P<0.05). Moreover, the mRNA transcriptional activity in the control group was also higher than that in the liriodendrin group (P<0.05). Because of the effect of liriodendrin, NF-κB pathway and apoptosis were downregulated in H9C2 cells which were exposed to ischemia-hypoxia. CONCLUSIONS: Liriodendrin may protect myocardial cells after myocardial infarction in rats by inhibiting the release of inflammatory factors, activation of the NF-κB pathway, and apoptosis.
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BACKGROUND: Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C). However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function. METHODS: Eighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [(3)H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks. RESULTS: Compared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased. CONCLUSION: Probucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions.
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Anticolesterolemiantes/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Lipoproteínas HDL/fisiología , Probucol/uso terapéutico , Transportador 1 de Casete de Unión a ATP , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Anticolesterolemiantes/farmacología , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Arildialquilfosfatasa/sangre , Aterosclerosis/metabolismo , Antígenos CD36/genética , Antígenos CD36/metabolismo , Células Cultivadas , Colesterol/sangre , Colesterol/metabolismo , Dieta Alta en Grasa , Expresión Génica , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Lipoproteínas HDL/farmacología , Hígado/metabolismo , Hígado/patología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Peroxidasa/sangre , Probucol/farmacología , Conejos , Distribución Aleatoria , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patología , Regulación hacia ArribaRESUMEN
BACKGROUND: To investigate the protective effect of resolvin D1 (RvD1) on aortic dissection (AD) in mice and explore the related mechanisms. METHODS: Mice were randomly divided into a blank group, model group, and RvD1 group. The RvD1 and model groups were administered 0.4% ß-aminopropionitrile (BAPN) solution, while the blank group was administered distilled water. When the experiment began, whether mice had AD was determined by echocardiogram. The RvD1 group was also administered RvD1 (30 µg/kg), while the model and blank groups were administered saline intraperitoneally. After 21 d, body weight trend and survival rate in the three groups were compared. The diameter of the ascending aorta of mice was detected by echocardiography. Then, the mice were sacrificed, and histopathological staining procedures were performed. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines and chemokines in blood and tissue, respectively. RESULTS: At 21 d, there was no statistically significant difference in body weight between three groups (P>0.05). The survival rate showed a significant difference between the RvD1 and model group (P<0.05). Echocardiography revealed that compared with the RvD1 and blank groups, aortic dilatation was significant in the model group. Pathological staining showed that the destruction of the aortic wall structure and inflammatory cell infiltration were more noticeable in the model group than in the RvD1 group. A slight disintegration of elastic fibers and collagen in the aorta was observed in the RvD1 group, and the aortic structure was clear. The results of ELISA showed that the inflammatory factors levels in the RvD1 group, although higher than those in blank group, were significantly decreased compared with the model group. The ELISA results of AD tissue showed that at 21 d, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the aorta were significantly decreased in the RvD1 group compared with the model group (P<0.05). CONCLUSIONS: Administration of RvD1 significantly delayed aortic dilation and disintegration and inhibited local macrophage and neutrophil infiltration in the early stages of aortic injury. Moreover, RvD1 significantly downregulated the expression of cytokines and chemokines in aortic tissues and serum and improved aortic remodeling.
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BACKGROUND: Stanford type A aortic dissection (TAAD) has a sudden onset and high mortality, and emergency total aortic arch replacement (TAAR) is the main treatment option for TAAD. The mortality rate of patients with postoperative acute kidney injury (AKI) combined with continuous renal replacement therapy (CRRT) is remarkable higher than that of patients without AKI. However, incidence of AKI and risk factors for CRRT following TAAR isn't entirely understood. METHODS: From October 2018 to March 2021, all patients with Stanford type A dissection who underwent total arch replacement surgery under MHCA were enrolled. According to whether CRRT treatment was performed, participants were divided into a CRRT group (n=49) and control group (n=72). Both groups incorporated the brain protection strategy of moderate hypothermia, and the left common carotid artery and the innominate artery were perfused anteriorly. Relevant medical data was collected. RESULTS: Age, gender, and a history of smoking and drinking were not significantly different between the 2 groups (P>0.1). There were statistical differences between the 2 groups in aortic sinus diameter and Bentall procedure (P≤0.05). Univariate analysis revealed that fresh frozen plasma was a protective factor (P<0.05) and the intraoperative transfusion volume of red blood cells, platelets, fresh frozen plasma, autologous blood used for intraoperative bleeding, aortic sinus diameter, and Bentall procedure were risk factors (P<0.1). Multivariate analysis showed that the Bentall procedure and intraoperative bleeding were risk factors for CRRT (P<0.05), and the aortic sinus diameter and intraoperative transfusion score were also risk factors for CRRT (P<0.05). Receiver operating characteristic (ROC) analysis demonstrated that the model of aortic sinus diameter and intraoperative transfusion score had more significantly different discriminatory powers. CONCLUSIONS: The Bentall procedure, intraoperative bleeding, aortic sinus diameter, and intraoperative transfusion score were risk factors for postoperative CRRT. The model of aortic sinus diameter and intraoperative transfusion score had more significantly different discriminatory powers.
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In this paper, we report the phylogeographic history of Clintoniaudensis Trautv. & Mey. (Liliaceae) inferred from two types of chloroplast DNA markers, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequences. Eighty samples were collected from 20 natural populations, 19 located in China and one in Japan, across the entire range of the species in East Asia. High genetic diversity (h(T)(PCR-RFLP)=0.972, h(T)(sequencing)=0.874) and significant differentiation (N(ST)(PCR-RFLP)=0.893, N(ST)(sequencing)=0.988 and G(ST)(PCR-RFLP)=0.777, G(ST)(sequencing)=0.978) were detected at the species level. These findings are consistent with a scenario of clonal reproduction and locally restricted gene exchange. The level of diversity of tetraploid populations was slightly greater than that of diploid populations. Significant molecular variation was found between tetraploids and diploids. Tetraploids may be autopolyploids and may have formed repeatedly in different locations. At least three regions of origin could be recognized. Twenty-six distinct haplotypes were identified. Haplotype frequency distributions were strongly skewed, with most haplotypes (n=25) represented by only one sample each and thus restricted to a single population. Non-overlapping distributions of cpDNA haplotypes and strong genetic differentiation among populations and/or different ploid level were consistent with the findings of a nested clade analysis, which inferred long-distance colonization as the major process influencing the spatial haplotype distribution of this species. Nested clade analysis showed that the 26 haplotypes formed two 3-step, four 2-step and eleven 1-step clades, with twelve clades showing significant geographical associations. Higher N(ST) than G(ST) (P<0.05) suggested a distinct phylogeographical pattern. Based on mismatch distribution analysis and neutrality tests, we found no evidence of population expansion in the species. Our analyses indicate that the history of C.udensis involved both long-distance migration and the tectonic events of Mountains in East Asia.
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ADN de Cloroplastos/genética , Evolución Molecular , Genética de Población , Liliaceae/genética , Filogenia , China , ADN de Plantas/genética , Diploidia , Variación Genética , Geografía , Haplotipos , Japón , Liliaceae/clasificación , Polimorfismo de Longitud del Fragmento de Restricción , Poliploidía , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Saruma henryi Oliv. (Aristolochiaceae) is an endangered herb endemic to China. In this study, chloroplast microsatellites (cpSSRs) and sequences of the atpB-rbcL intergenic spacers were employed to reveal its genetic diversity and phylogeographic patterns. We detected high within-species genetic diversity (H(T)=0.939 for cpSSR; H(T)=0.862 for atpB-rbcL) and pronounced among-population genetic differentiation (H(S)=0.182, G(ST)=0.811, R(ST)=0.9, F(ST)=0.93 for cpSSR; H(S)=0.238, G(ST)=0.724, N(ST)=0.758, F(ST)=0.79 for atpB-rbcL) with a strong phylogeographic pattern (R(ST)>G(ST), P<0.01 for cpSSR; N(ST)>G(ST), U=0.25 for atpB-rbcL). Eleven haplotypes were distinguished by cpSSRs and atpB-rbcL intergenic spacers, respectively. The molecular phylogenetic data, together with the geographic distribution of the haplotypes, suggested the existence of multiple localized glacial refugia in Mts. Qinling, eastern Mts. Bashan and the southeastern edge of Yunnan-Guizhou Plateau. Nested clade analysis (NCA) and population genetic analyses supported the limited gene flow (caused by low dispersal capacity and complex topography of its habitats) as the major factor responsible for the strong population differentiation and phylogeographic pattern. Past fragmentation and allopatric fragmentation were inferred as important processes responsible for the modern phylogeograhpic pattern. In addition, contiguous range expansions occurred in western Mts. Qinling and eastern Mts. Bashan.
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Aristolochiaceae/genética , Evolución Molecular , Variación Genética , Filogenia , Aristolochiaceae/clasificación , China , ADN de Cloroplastos/genética , ADN de Plantas/genética , ADN Espaciador Ribosómico/genética , Flujo Génico , Genética de Población , Haplotipos , Repeticiones de Microsatélite , Filogeografía , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To analyze the risk factors in the patients over 65 years old undergoing off-pump coronary artery bypass grafting (OPCAG) as grouped by postoperative creatinine clearance rate (Ccr). METHODS: A total of 462 consecutive patients over 65 years old undergoing OPCAG from January 2007 to December 2008 were recruited. They were divided into 3 groups by renal functions: normal, minor injury and moderate-severe injury. The risk factors were analyzed by a comparison of postoperative complications, duration of intubation, stay of intensive care unit and mortality rate, et al. RESULTS: There was no significant difference between the parameters of preoperative complications, left ventricle ejection fraction (LVEF), left ventricle end diastolic diameter (LVEDD) and lipid level, et al. And the postoperative complications were closely related to the decrease of Ccr and the increases of B-type natriuretic peptide (BNP), CKMB, total bilirubin (TBIL) and LVEDD (P < 0.01 for each). CONCLUSIONS: The moderate-severe renal injury (Ccr < 50 ml/min) with the abnormal levels of TBIL, BNP and LVEDD are the risk factors for a worse prognosis in OPCAG patients over 65 years old. Because of the injury of OPCAG, we should pay attention to patients with abnormal renal function (Ccr < 80 ml/min) to prevent an onset of severe complications.
Asunto(s)
Puente de Arteria Coronaria Off-Pump/efectos adversos , Creatinina/metabolismo , Riñón/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Riñón/metabolismo , Pruebas de Función Renal , Masculino , Tasa de Depuración Metabólica , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Type I diabetes (T1D) is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas, resulting in dysregulation of tissue homeostasis, mechanobiological properties, and the immune response. The streptozotocin (STZ)-induced mouse model exhibits multiple features of human T1D and enables mechanistic analysis of disease progression. However, the relationship between the mechanochemical signaling regulation of STZ-induced T1D and macrophage migration and phagocytosis is unclear. AIM: To study the mechanochemical regulation of STZ-induced macrophage response on pancreatic beta islet cells to gain a clearer understanding of T1D. METHODS: We performed experiments using different methods. We stimulated isolated pancreatic beta islet cells with STZ and then tested the macrophage migration and phagocytosis. RESULTS: In this study, we discovered that the integrin-associated surface factor CD47 played a critical role in immune defense in the STZ-induced T1D model by preventing pancreatic beta islet inflammation. In comparison with healthy mice, STZ-treated mice showed decreased levels of CD47 on islet cells and reduced interaction of CD47 with signal regulatory protein α (SIRPα), which negatively regulates macrophage-mediated phagocytosis. This resulted in weakened islet cell immune defense and promoted macrophage migration and phagocytosis of target inflammatory cells. Moreover, lipopolysaccharide-activated human acute monocytic leukemia THP-1 cells also exhibited enhanced phagocytosis in the STZ-treated islets, and the aggressive attack of the inflammatory islets correlated with impaired CD47-SIRPα interactions. In addition, CD47 overexpression rescued the pre-labeled targeted cells. CONCLUSION: This study indicates that CD47 deficiency promotes the migration and phagocytosis of macrophages and provides mechanistic insights into T1D by associating the interactions between membrane structures and inflammatory disease progression.