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This study aimed to enhance extracellular polysaccharide (EPS) production in Cordyceps militaris by constructing a quorum sensing (QS) system to regulate the expression of biosynthetic enzyme genes, including phosphoglucomutase, hexokinase, phosphomannomutase, polysaccharide synthase, and UDP-glucose 4-epimerase genes. The study found higher EPS concentrations in seven recombinant strains compared to the wild-type C. militaris, indicating that the overexpression of key enzyme genes increased EPS production. Among them, the CM-pgm-2 strain exhibited the highest EPS production, reaching a concentration of 3.82 ± 0.26 g/L, which was 1.52 times higher than the amount produced by the wild C. militaris strain. Additionally, the regulatory effects of aromatic amino acids on the QS system of the CM-pgm-2 strain were investigated. Under the influence of 45 mg/L tryptophan, the EPS production in CM-pgm-2 reached 4.75 ± 0.20 g/L, representing a 1.90-fold increase compared to wild C. militaris strains. This study provided an effective method for the large-scale production of EPSs in C. militaris, and opened up new avenues for research into fungal QS mechanisms.
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Cordyceps , Percepción de Quorum , Cordyceps/genética , Cordyceps/metabolismo , Cordyceps/crecimiento & desarrollo , Polisacáridos/metabolismo , Polisacáridos/biosíntesis , Regulación Fúngica de la Expresión Génica , Polisacáridos Fúngicos/biosíntesis , Polisacáridos Fúngicos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Triptófano/metabolismo , Triptófano/biosíntesisRESUMEN
Background and Objectives: The physiological phenomenon peculiar to women, namely menopause, makes the occurrence of left ventricular hypertrophy (LVH) in postmenopausal hypertensive women more characteristic. Less is known about the risk of developing LVH in Chinese postmenopausal hypertensive women. Thus, the present study was intended to design a nomogram for predicting the risk of developing LVH in Chinese postmenopausal hypertensive women. Materials and Methods: Postmenopausal hypertensive women aged between 49 and 68 years were divided into either the training set (n = 550) or the validation set (n = 284) in a 2:1 ratio. Patients in the validation set were followed up for one year. A stepwise multivariable logistic regression model was used to assess the predictors of LVH in postmenopausal women with hypertension. The best-fit nomogram was executed using R software. The calibration and decision curve were employed to verify the predictive accuracy of the nomogram. The results were evaluated in the validation set. Results: Menopause age (OR = 0.929, 95% CI 0.866-0.998, p = 0.044), BMI (OR = 1.067, 95% CI 1.019-1.116, p = 0.005), morning systolic blood pressure (SBP: OR = 1.050, 95% CI 1.032-1.069, p = 0.000), morning diastolic BP (DBP OR = 1.055, 95% CI 1.028-1.083, p = 0.003), angiotensin II receptor blocker (ARB) utilization rate (OR = 0.219, 95% CI 0.131-0.365, p = 0.000), LDL-C (OR = 1.460, 95% CI 1.090-1.954, p = 0.011) and cardio-ankle vascular index (CAVI) (OR = 1.415, 95% CI 1.139-1.757, p = 0.028) were associated with LVH in postmenopausal hypertension patients. The nomogram model was then developed using these variables. The internal validation trial showed that the nomogram model described herein had good performance in discriminating a C-index of 0.881 (95% CI: 0.837-0.924) and high quality of calibration plots. External validation of LVH-predictive nomogram results showed that the area under the ROC curve was 0.903 (95%CI 0.900-0.907). Conclusions: Our results indicate that the risk prediction nomogram model based on menopausal age, BMI, morning SBP, morning DBP, ARB utilization rate, LDL-C and CAVI has good accuracy and may provide useful references for the medical staff in the intuitive and individualized risk assessment in clinical practice.
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Hipertensión , Hipertrofia Ventricular Izquierda , Humanos , Femenino , Persona de Mediana Edad , Anciano , Hipertrofia Ventricular Izquierda/complicaciones , Antagonistas de Receptores de Angiotensina , LDL-Colesterol , Pueblos del Este de Asia , Nomogramas , Posmenopausia , Inhibidores de la Enzima Convertidora de Angiotensina , Hipertensión/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Postmenopausal women tend to experience significant changes in left ventricular diastolic function (LVDF). However, there are conflicting reports about LVDF between postmenopausal women on hormone replacement therapy (HRT) and those not on HRT. This meta-analysis is to evaluate the effects of HRT on LVDF in postmenopausal women. METHODS: We conducted a systemic review of randomized controlled trials published up to December 31 2019 using Embase, Pubmed, and the Cochrane library database. RESULTS: Eight studies involving 668 postmenopausal women were identified. Our analysis indicated that the ratio of the peak velocity during early filing to late filling from atrial contraction improvement in HRT group was better than that in placebo group (MD 0.20, 95%CI 0.12 to 0.28). There was a significant reduction in deceleration time and left ventricular mass index in HRT group compared with placebo group (MD -21.01, 95%CI -40.11 to -1.91 vs MD -8.26, 95%CI -14.10 to -2.42). No significant difference was observed in left ventricular end systole diameter (MD 0.80, 95%CI -0.72 to 2.31), left ventricular end diastole diameter (MD -0.07, 95%CI -1.25 to 1.10), left atrial size (MD -0.33, 95%CI -1.34 to 0.68)and the isovolumic relaxation time (MD -12.08, 95%CI -27.65 to 3.5). CONCLUSIONS: Our meta-analysis illustrated that postmenopausal women seem to obtain more beneficial effects from HRT on LVDF, though future studies are required to elucidate the specific mechanisms for this phenomenon.
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Terapia de Reemplazo de Estrógeno , Posmenopausia/fisiología , Función Ventricular Izquierda/fisiología , Diástole , Femenino , HumanosRESUMEN
BACKGROUND AND AIMS: Vitamin E (tocochromanol) is a lipid-soluble antioxidant and an essential nutrient for human health. Among cereal crops, barley (Hordeum vulgare) contains a high level of vitamin E, which includes both tocopherols and tocotrienols. Although the vitamin E biosynthetic pathway has been characterized in dicots, such as Arabidopsis, which only accumulate tocopherols, knowledge regarding vitamin E biosynthesis in monocots is limited because of the lack of functional mutants. This study aimed to obtain gene knockout mutants to elucidate the genetic control of vitamin E composition in barley. METHODS: Targeted knockout mutations of HvHPT and HvHGGT in barley were created with CRISPR/Cas9-enabled genome editing. High-performance liquid chromatography (HPLC) was performed to analyse the content of tocochromanol isomers in transgene-free homozygous Hvhpt and Hvhggt mutants. KEY RESULTS: Mutagenesis efficiency among T0 regenerated plantlets was 50-65 % as a result of two simultaneously expressed guide RNAs targeting each gene; most of the mutations were stably inherited by the next generation. The transgene-free homozygous mutants of Hvhpt and Hvhggt exhibited decreased grain size and weight, and the HvHGGT mutation led to a shrunken phenotype and significantly lower total starch content in grains. HPLC analysis revealed that targeted mutation of HvHPT significantly reduced the content of both tocopherols and tocotrienols, whereas mutations in HvHGGT completely blocked tocotrienol biosynthesis in barley grains. Transient overexpression of an HvHPT homologue in tobacco leaves significantly increased the production of γ- and δ-tocopherols, which may partly explain why targeted mutation of HvHPT in barley grains did not eliminate tocopherol production. CONCLUSIONS: Our results functionally validated that HvHGGT is the only committed gene for the production of tocotrienols, whereas HvHPT is partly responsible for tocopherol biosynthesis in barley.
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Hordeum , Tocotrienoles , Sistemas CRISPR-Cas/genética , Edición Génica , Hordeum/genética , Humanos , Tocoferoles , Vitamina ERESUMEN
BACKGROUND: To investigate the clinical value of heart failure echocardiography index (HFEI) in evaluating the cardiac function and predicting the prognosis of patients with different types of heart failure (HF). METHODS: Four hundred eighty-nine consecutively admitted HF patients were divided into three groups: HF with reduced ejection (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The baseline characteristics and ultrasound indexes were compared between the three groups. The correlation between HFEI and one-year risk of adverse events was compared by multivariate logistic regression. The clinical value of HFEI and plasma level of NT-proBNP in assessing the prognosis of patients with chronic heart failure (CHF) was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: HFEI in HFrEF was significantly higher than that in HFmrEF and HFpEF. Multivariate regression analysis indicated that HFEI and plasma level of NT-proBNP were independent risk factors for predicting the short-time prognosis of HF patients. The ROC curve indicated that the HFEI cutoff level of 3.5 and the plasma NT-proBNP level of 3000 pg/ml predicted a poor prognosis of CHF patients with a sensitivity of 64% and a specificity of 75% vs. 68 and 65%. CONCLUSION: HFEI can comprehensively evaluate the overall cardiac function of patients with various types of HF, and may prove to be an important index of assessing the prognosis of HF patients.
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Ecocardiografía , Insuficiencia Cardíaca/diagnóstico por imagen , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
In this report, structural characterization, aptamer stability and thrombin of a new modified thrombin-ligand complex binding aptamer (TBA) containing anti-guanine bases and a loop position locked nucleic acid (LNA) are presented. NMR, circular dichroic spectroscopy and molecular modeling were used to characterize the three-dimensional structure of two G-quadruplexes. LNA-modification of the anti-guanosines yields G-quadruplexes that show affinity and inhibitory activity toward thrombin, whereas LNA-modification of a thymine nucleotide in the TGT loop increases the thermal stability of TBA. As assessed by denatured PAGE electrophoresis, all modified aptamers display an increase in environmental stability. The prothrombin time assay and fibrinogen assay showed that the aptamers still had good inhibitory activity, and 15 of them had the longest PT time. Therefore, the LNA modification is well suited to improve the physicochemical and biological properties of the native thrombin-binding aptamer.
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Aptámeros de Nucleótidos/química , Simulación de Dinámica Molecular/normas , Oligonucleótidos/química , Relación Estructura-ActividadRESUMEN
An electrochemical biosensor that used an aptamer as a biological element was constructed to detect endotoxin. Biolayer interferometry was used to obtain the affinity constant of an aptamer for lipopolysaccharide, which had an equilibrium dissociation constant of 22.9 nM. The amine-terminated aptamer was then assembled on a gold electrode surface using 3-mercaptopropionic acid as an intermediate linker. The modification of the gold electrode was confirmed by cyclic voltammetry and electrochemical impedance spectroscopy. In the range of 0.001-1 EU/mL, the increase in electron transfer resistance of the biosensor was linear with the logarithmic value of the endotoxin concentration. The constructed biosensor exhibits sensitivity and a low limit of detection.
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Aptámeros de Nucleótidos/química , Técnicas Biosensibles , Técnicas Electroquímicas , Endotoxinas/análisis , Aminas/química , Electrodos , Oro/químicaRESUMEN
Human thymic stromal lymphopoietin (hTSLP) protein plays a central role in inflammation. Characterizing properties of hTSLP requires a recombinant overexpression system that produces correctly folded, active hTSLP. In this report, an efficient overexpression system for the production of hTSLP was developed. We constructed expression plasmids of the full-length hTslp gene with or without the signal peptide and transformed the plasmids into Escherichia coli. The design of the recombinant proteins included an N-terminal His-tag, which facilitated purification. An affinity gradient elution method was used to improve recovery and concentration levels of denatured hTSLP, with 90% purity observed following affinity chromatography. Refolding of the denatured hTSLP was tested using four different protein refolding approaches. The optimal refolding conditions involved stepwise buffer exchanges to reduce the urea concentration from 4 to 0 M in 50 mM Tris (pH 8.0), 1 mM EDTA, 50 mM NaCl, 10% glycerol, 400 mM L-Arg, 0.2 mM oxidized glutathione, and 2 mM reduced glutathione. The activity of the refolded recombinant hTSLP protein was measured by an ELISA assay. Interestingly, the presence of N-terminal signal peptide inhibited the overexpression of hTSLP in E. coli. The amount of recombinant hTSLP protein purified reached a level of 2.52 × 10-3 mg/L.
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Citocinas/genética , Escherichia coli/genética , Clonación Molecular/métodos , Citocinas/química , Humanos , Plásmidos/genética , Replegamiento Proteico , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Solubilidad , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: High content of (1,3;1,4)-ß-d-glucan in barley grains is regarded as an undesirable factor affecting malting potential, brewing yield and feed utilization. Production of thermostable bacterial (1,3;1,4)-ß-glucanase in transgenic barley grain or supplementation of exogenous bacterial (1,3;1,4)-ß-glucanase has been used to improve malt and feed quality. The aim of the present study was to investigate the effect of over-expression of an endogenous (1,3;1,4)-ß-glucanase on ß-glucan content and grain composition in barley. RESULTS: A construct containing full-length HvGlb2 cDNA encoding barley (1,3;1,4)-ß-glucanase isoenzyme EII under the control of a promoter of barley D-Hordein gene Hor3-1 was introduced into barley cultivar Golden Promise via Agrobacterium-mediated transformation, and transgenic plants were regenerated after hygromycin selection. The T2 generation of proHor3:HvGlb2 transgenic lines showed increased activity of (1,3;1,4)-ß-glucanase in grains. Total ß-glucan content was reduced by more than 95.73% in transgenic grains compared with the wild-type control. Meanwhile, over-expression of (1,3;1,4)-ß-glucanase led to an increase in 1000-grain weight, which might be due to elevated amounts of starch in the grain. CONCLUSION: Manipulating the expression of (1,3;1,4)-ß-glucanase EII can control the ß-glucan content in grain with no apparent harmful effects on grain quality of transgenic plants. © 2016 Society of Chemical Industry.
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Glucanos/metabolismo , Glicósido Hidrolasas/genética , Hordeum/metabolismo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/metabolismo , Almidón/metabolismo , Glucanos/química , Glicósido Hidrolasas/metabolismo , Hordeum/química , Hordeum/enzimología , Hordeum/genética , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética , Semillas/química , Semillas/enzimología , Semillas/metabolismoRESUMEN
OBJECTIVES: To select aptamers for endotoxin separation from a 75-nucleotide single-stranded DNA random library using systematic evolution of ligands by exponential enrichment. RESULTS: After 15 rounds of selection, the final pool of aptamers was specific to endotoxin. Structural analysis of aptamers that appeared more than once suggested that one aptamer can form a G-quartet structure. Tests for binding affinity and specificity showed that this aptamer exhibited a high affinity for endotoxin. Using this aptamer, aptamer-magnetic beads were designed to separate endotoxin. CONCLUSIONS: Using these aptamer-magnetic beads, a new method to separate endotoxin was developed to enable specific separation of endotoxin that can be applied to drug and food products.
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Aptámeros de Nucleótidos/aislamiento & purificación , Aptámeros de Nucleótidos/metabolismo , Endotoxinas/aislamiento & purificación , Endotoxinas/metabolismo , Evolución Molecular Dirigida , Técnica SELEX de Producción de AptámerosRESUMEN
Penicillium macrosclerotiorum was isolated for the first time from the leaves of Ilex pubescens Hook. et Arn (VSN-2022-03-18-001) and found to produce bioactive compounds. Seven compounds were obtained from the fermentation broth and mycelia of P. macrosclerotiorum and identified as palmitic acid (1), methyl 6-acetyl-5,7,8-trihydroxy-4-methoxy-2-naphthoate (2), ergosterol (3), daidzein (4), oleuropein (5), pedunculoside (6) and acteoside (7). Compounds 3, 4 and 7 exhibited antioxidant activity against diphenyl picryl hydrazinyl with IC50 values of 58.06, 2.58 and 12.01 µg/mL, respectively. Compounds 3, 5 and 7 exhibit inhibitory activity against Escherichia coli with MIC values of 0.78, 3.13 and 3.13 mg/mL, while compounds 2, 3, 4, 5, 6 and 7 exhibited inhibitory effect on Candida albicans with MIC values of 0.20, 0.20, 0.39, 0.63, 0.78 and 0.78 mg/mL, respectively. Furthermore, Compound 4 effectively inhibited HepG2 cells, showing an IC50 of 34.03 µg/mL.
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Cardiovascular (CV) diseases and tumors are best known for its high morbidity and mortality worldwide. There is a growing recognition of the association between CV diseases and tumorigenesis. In addition to CV damage caused by anti-tumor drugs and tumor-induced organ dysfunction, CV events themselves and their treatment may also have a role in promoting tumorigenesis. Therefore, Therefore, the diagnosis and treatment of the two kinds of diseases have entered the era of clinical convergence. Emerging evidence indicates significant biologic overlap between cancer and CV diseases, with the recognition of shared biologic mechanisms. Neutrophil extracellular traps (NETs) represent an immune mechanism of neutrophils promoting the development of tumors and their metastasis. It has been recently demonstrated that NETs exist in various stages of hypertension and heart failure, exacerbating disease progression. At present, most studies focus on the biological role of NETs in CV diseases and tumor respectively, and there are relatively few studies on the specific regulatory mechanisms and effects of NETs in cardiovascular diseases associated with tumors. In this narrative review, we summarize some recent basic and clinical findings on how NETs are involved in the pathogenesis of cardiovascular diseases associated with tumors. We also highlight that the development of treatments targeting NETs may be one of the effective ways to prevent and treat cardiovascular diseases associated with tumors.
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Enfermedades Cardiovasculares , Trampas Extracelulares , Neoplasias , Humanos , AnimalesRESUMEN
Recently, there has been increasing interest in the use of bacteria for cancer therapy due to their ability to selectively target tumor sites and inhibit tumor growth. However, the complexity of the interaction between bacteria and tumor cells evokes unpredictable therapeutic risk, which induces inflammation, stimulates the up-regulation of cyclooxygenase II (COX-2) protein, and stimulates downstream antiapoptotic gene expression in the tumor microenvironment to reduce the antitumor efficacy of chemotherapy and immunotherapy. In this study, we encapsulated celecoxib (CXB), a specific COX-2 inhibitor, in liposomes anchored to the surface of Escherichia coli Nissle 1917 (ECN) through electrostatic absorption (C@ECN) to suppress ECN-induced COX-2 up-regulation and enhance the synergistic antitumor effect of doxorubicin (DOX). C@ECN improved the antitumor effect of DOX by restraining COX-2 expression. In addition, local T lymphocyte infiltration was induced by the ECN to enhance immunotherapy efficacy in the tumor microenvironment. Considering the biosafety of C@ECN, a hypoxia-induced lysis circuit, pGEX-Pvhb-Lysis, was introduced into the ECN to limit the number of ECNs in vivo. Our results indicate that this system has the potential to enhance the synergistic effect of ECN with chemical drugs to inhibit tumor progression in medical oncology.
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The simultaneous sensing and remediation of multiple heavy metal ions in wastewater or soil with microorganisms is currently a significant challenge. In this study, the microorganism Bacillus subtilis was used as a chassis organism to construct two genetic circuits for sensing and adsorbing heavy-metal ions. The engineered biosensor can sense three heavy metal ions (0.1-75 µM of Pb2+ and Cu2+, 0.01-3.5 µM of Hg2+) in situ real-time with high sensitivity. The engineered B. subtilis TasA-metallothionein (TasA-MT) biofilm can specifically adsorb metal ions from the environment, exhibiting remarkable removal efficiencies of 99.5% for Pb2+, 99.9% for Hg2+and 99.5% for Cu2+ in water. Furthermore, this engineered strain (as a biosensor and absorber of Pb2+, Cu2+, and Hg2+) was incubated with biochar to form a hybrid biofilm@biochar (BBC) material that could be applied in the bioremediation of heavy metal ions. The results showed that BBC material not only significantly reduced exchangeable Pb2+ in the soil but also reduced Pb2+ accumulation in maize plants. In addition, it enhanced maize growth and biomass. In conclusion, this study examined the potential applications of biosensors and hybrid living materials constructed using sensing and adsorption circuits in B. subtilis, providing rapid and cost-effective tools for sensing and remediating multiple heavy metal ions (Pb2+, Hg2+, and Cu2+).
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Carbón Orgánico , Mercurio , Metales Pesados , Contaminantes del Suelo , Bacillus subtilis , Biodegradación Ambiental , Plomo , Metales Pesados/análisis , Iones , Suelo , Contaminantes del Suelo/análisisRESUMEN
OBJECTIVE: To evaluate the impact of sacubitril/valsartan on blood pressure (BP), ventricular structure, and myocardial fibrosis compared with valsartan in perimenopausal hypertensive women. METHODS: This prospective, randomized, actively controlled, open-label study included 292 women with perimenopausal hypertension. They were randomly divided into two groups: sacubitril/valsartan 200âmg once daily and valsartan 160âmg once daily for 24âweeks. The relevant indicators of ambulatory BP, echocardiography, and myocardial fibrosis regulation were assessed at baseline and at 24âweeks. RESULTS: The 24-h mean SBP after 24âweeks of treatment was 120.08â±â10.47âmmHg in the sacubitril/valsartan group versus 121.00â±â9.76âmmHg in the valsartan group ( P â=â0.457). After 24âweeks of treatment, there was no difference in central SBP between the sacubitril/valsartan and valsartan groups (117.17â±â11.63 versus 116.38â±â11.58, P â=â0.568). LVMI in the sacubitril/valsartan group was lower than that in the valsartan group at week 24 ( P â=â0.009). LVMI decreased by 7.23âg/m 2 from the baseline in the sacubitril/valsartan group and 3.70âg/m 2 in the valsartan group at 24âweeks ( P â=â0.000 versus 0.017). A statistically significant difference in LVMI between the two groups was observed at 24âweeks after adjusting for the baseline LVMI ( P â=â0.001). The levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CT-GF) and transforming growth factor-ß (TGF-ß) were reduced in the sacubitril/valsartan group compared with the baseline ( P â=â0.000, 0.005, and 0.000). LVMI between the two groups was statistically significant at 24âweeks after correcting for confounding factors 24-h mean SBP and 24-h mean DBP ( P â=â0.005). The LVMI, serum TGF-ß, α-SMA, and CT-GF remained statistically significant between the two groups after further correcting the factors of age, BMI, and sex hormone levels ( P â<â0.05). CONCLUSION: Sacubitril/valsartan could reverse ventricular remodeling more effectively than valsartan. The different effects of these two therapies on ventricular remodeling in perimenopausal hypertensive women might be because of their different effects on the down-regulation of fibrosis-related factors.
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Insuficiencia Cardíaca , Hipertensión , Femenino , Humanos , Aminobutiratos/farmacología , Aminobutiratos/uso terapéutico , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Perimenopausia , Estudios Prospectivos , Valsartán , Remodelación VentricularRESUMEN
Significance: Cardiovascular diseases are seen to be a primary cause of death, and their prevalence has significantly increased across the globe in the past few years. Several studies have shown that cell death is closely linked to the pathogenesis of cardiovascular diseases. Furthermore, many molecular and cellular mechanisms are involved in the pathogenesis of the cardiac cell death mechanism. One of the factors that played a vital role in the pathogenesis of cardiac cell death mechanisms included the early growth response-1 (Egr-1) factor. Recent Advances: Studies have shown that abnormal Egr-1 expression is linked to different animal and human disorders like heart failure and myocardial infarction. The biosynthesis of Egr-1 regulates its activity. Egr-1 can be triggered by many factors such as serum, cytokines, hormones, growth factors, endotoxins, mechanical injury, hypoxia, and shear stress. It also displays a pro-apoptotic effect on cardiac cells, under varying stress conditions. EGR1 mediates a broad range of biological responses to oxidative stress and cell death by combining the acute changes occurring in the cellular environment with sustained changes in gene expression. Future Directions: The primary regulatory role played by the Egr-1-targeting DNAzymes, microRNAs, and oligonucleotide decoy strategies in cardiovascular diseases were identified to provide a reference to identify novel therapeutic targets for cardiovascular diseases.
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The endoplasmic reticulum (ER), an essential organelle in eukaryotic cells, is widely distributed in myocardial cells. The ER is where secreted protein synthesis, folding, post-translational modification, and transport are all carried out. It is also where calcium homeostasis, lipid synthesis, and other processes that are crucial for normal biological cell functioning are regulated. We are concerned that ER stress (ERS) is widespread in various damaged cells. To protect cells' function, ERS reduces the accumulation of misfolded proteins by activating the unfolded protein response (UPR) pathway in response to numerous stimulating factors, such as ischemia or hypoxia, metabolic disorders, and inflammation. If these stimulatory factors are not eliminated for a long time, resulting in the persistence of the UPR, it will aggravate cell damage through a series of mechanisms. In the cardiovascular system, it will cause related cardiovascular diseases and seriously endanger human health. Furthermore, there has been a growing number of studies on the antioxidative stress role of metal-binding proteins. We observed that a variety of metal-binding proteins can inhibit ERS and, hence, mitigate myocardial damage.
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Ischemic heart failure (HF) is one of the leading causes of global morbidity and mortality; blocking the apoptotic cascade could help improve adverse outcomes of it. RNA-binding motif protein 25 (RBM25) is an RNA-binding protein related to apoptosis; however, its role remains unknown in ischemic HF. The main purpose of this study is to explore the mechanism of RBM25 in ischemic HF. Establishing an ischemic HF model and oxygen-glucose deprivation (OGD) model. ELISA was performed to evaluate the BNP level in the ischemic HF model. Echocardiography and histological analysis were performed to assess cardiac function and infarct size. Proteins were quantitatively and locationally analyzed by western blotting and immunofluorescence. The morphological changes of endoplasmic reticulum (ER) were observed with ER-tracker. Cardiac function and myocardial injury were observed in ischemic HF rats. RBM25 was elevated in cardiomyocytes of hypoxia injury hearts and localized in nucleus both in vitro and in vivo. In addition, cell apoptosis was significantly increased when overexpressed RBM25. Moreover, ER stress stimulated upregulation of RBM25 and promoted cell apoptosis through the CHOP related pathway. Finally, inhibiting the expression of RBM25 could ameliorate the apoptosis and improve cardiac function through blocking the activation of CHOP signaling pathway. RBM25 is significantly upregulated in ischemic HF rat heart and OGD model, which leads to apoptosis by modulating the ER stress through CHOP pathway. Knockdown of RBM25 could reverse apoptosis-mediated cardiac dysfunction. RBM25 may be a promising target for the treatment of ischemic HF.
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Hipoxia , Miocitos Cardíacos , Ratas , Animales , Línea Celular , Miocitos Cardíacos/patología , Hipoxia/patología , Oxígeno/metabolismo , Apoptosis/fisiología , Estrés del Retículo EndoplásmicoRESUMEN
The biological function and evolution of microRNAs (miRNAs), an important class of noncoding regulatory genes, have attracted wide interest. However, their evolutionary impact on gene order rearrangements remains unknown. We examined the gene-order stability of miRNA-neighboring regions by a comparative human-mouse genomic analysis and found that the neighboring genes of human miRNAs tend to have a conserved gene order. This observation cannot be attributed to the functional bias of neighboring genes, and is a unique characteristic of miRNAs but not other noncoding RNAs. Our findings suggest that mammalian miRNAs stabilize the genomic architecture in evolution.
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Orden Génico , MicroARNs/genética , Animales , Hibridación Genómica Comparativa , Evolución Molecular , Redes Reguladoras de Genes , Genoma , Humanos , Mamíferos/genética , RatonesRESUMEN
Immunoglobulin G (IgG) antibodies are used extensively for analytical, diagnostic, and therapeutic applications. However, there are some disadvantages to purify IgG antibodies by protein A and G affinity chromatography. Therefore, it is necessary to find an effective alternative and nonchromatographic method to purify IgG. Dextran microparticles were activated and coupled with sulfamethazine to form sulfamethazine-affinity carriers. Then the carriers were used to purify IgG by affinity filtration. Quantitative and qualitative determination proved that sulfamethazine would successfully bond to the surface of dextran microparticles with a density of 85.5 µmol/g (wet). Affinity carriers were proved to withstand high shear force and reveal rare sulfamethazine leakage under filtration conditions between pH 3 to 11. The maximum IgG-binding capacity of affinity carriers was 8.03 mg IgG/g (wet). The affinity filtration process obtained a recovery yield above 80% and purity above 90%. Thus, this work involved in both the advantages of membrane filtration and affinity purification. The results, for the first time, proved that it is possible to use the small ligand sulfamethazine for affinity filtration of IgG. It is an attractive alternative to conventional protein A or G affinity chromatography.