RESUMEN
Myocardial infarction (MI) is indicated by the symptoms like sharp chest pain, sweating, palpitations, and nervousness finally leading to heart attack. MI occurs mainly due to the risk factors like smoking, elevated blood pressure, diabetes, hypercholesterolemia, obesity, decreased HDL level, elevated LDL level, hyperlipoproteinemia and aging consequently leads to demandable coronary blood supply, oxidative stress, and acute necrosis of the myocardium. Cardioprotective potential of the phloroglucinol (PG) was assessed by treating isoprenaline hydrochloride (ISO; 85 mg/kg b.w., s.c.) induced MI model in rats. Pretreatment with PG in a dose of 30 mg/kg was done for 28 days and followed by ISO (for MI induction) on 29th and 30th days, exhibited decline in the abnormalities in the ECG patterns, cardiac marker enzymes, enzymic and nonenzymic antioxidants, lipid peroxidation, lipid profiles, and histopathological investigations compared to isoprenaline alone treated group. On the whole, the present investigations elucidate the significance of PG in alleviating the pathological process and appreciably prevent the induction of MI in experimental rats.
Asunto(s)
Cardiotónicos/farmacología , Infarto del Miocardio/prevención & control , Floroglucinol/farmacología , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Electrocardiografía , Corazón/efectos de los fármacos , Isoproterenol , Peroxidación de Lípido/efectos de los fármacos , Lípidos/sangre , Masculino , Infarto del Miocardio/sangre , Miocardio/enzimología , Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , Ratas WistarRESUMEN
Chrysophanol (CH), extracted from plants of Rheum genus, possesses various pharmacological effects including anti-inflammatory activity. The purpose of the present study was to evaluate the protective effects and the underlying mechanisms of CH on ovalbumin (OVA)-induced asthma in mice. Fifty mice were randomly assigned to five experimental groups: control group, model group, dexamethasone (2 mg/kg) group and CH (5 and 10 mg/kg) groups. The number of eosinophil cells and the production of interleukin-6 (IL-6), IL-1ß, IL-17 A and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) were measured. In addition, pulmonary histopathology, airway resistance (Raw), T-helper17 (Th17) cells frequency and RORγt expression were evaluated. Our study demonstrated that CH effectively decreased eosinophil count and inflammatory cytokines production in BALF. In addition, treatment with CH significantly inhibited the Raw, Th17 percentage and RORγt expression in OVA-induced animals compared with those in model group. Histological studies also demonstrated that CH significantly suppressed OVA-induced eosinophilia in lung tissue compared with model group. Our findings supported that CH can prevent allergic asthma in the mouse model.
Asunto(s)
Antraquinonas/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Ovalbúmina/inmunología , Células Th17/efectos de los fármacos , Resistencia de las Vías Respiratorias/efectos de los fármacos , Resistencia de las Vías Respiratorias/inmunología , Animales , Antraquinonas/administración & dosificación , Antraquinonas/aislamiento & purificación , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Asma/inmunología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Citometría de Flujo , Ratones Endogámicos BALB C , Rheum/química , Células Th17/inmunologíaRESUMEN
Background: Understanding the correlation between female breast cancer (BC) and the prevalence of coronary heart disease (CHD) is important for developing prevention strategies and reducing the burden of female social disease. This study aimed to evaluate the relationship between BC and CHD using data from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018. Methods: The study cohort included 16,149 eligible non-pregnant female participants aged 20 years or older. Logistic regression was used to analyze the relationship between BC and CHD, excluding the interaction between covariates and BC through hierarchical subgroup analysis. Results: The study found that participants with BC had a 2.30 times greater risk of developing CHD compared to those without BC [95% confidence interval (CI): 2.29-2.31]. After adjusting for all included covariates, BC was still significantly associated with CHD risk (odds ratio: 1.11, 95% CI: 1.10-1.12). When participants were stratified by age, education level, and prevalence of hypertension, it was evident that participants with BC had a higher risk of developing CHD compared to those without BC, although the effect of BC on CHD varied across stratification. Conclusions: Our study demonstrates the close relationship between CHD and female BC. Therefore, it is necessary to screen patients with CHD for BC and monitor BC survivors for the long-term risk of developing CHD.
RESUMEN
AIMS: Vascular smooth muscle cells (VSMCs) are involved in the pathogenesis of many human cardiovascular diseases. They modulate their phenotype from "contractile" to "synthetic" in response to changes in local environmental cues. How glutamine regulates the differentiation of VSMCs and the underlying mechanisms remain largely unknown. MAIN METHODS: Here, we explored the effects of various doses of glutamine (0 mM, 1 mM, 2 mM, and 4 mM) on the proliferation, migration, and phenotypic switch of human VSMCs in vitro. Glutamine dose-dependently enhanced VSMC proliferation, and markedly increased VSMC migration. KEY FINDINGS: Notably, glutamine promoted the phenotypic switch of VSMCs towards a synthetic phenotype, as evidenced by significantly decreased expression of contractile markers myosin heavy chain 11 (MYH11) and calponin while increased expression of synthetic markers collagen I and vimentin. Importantly, these changes upon glutamine treatments were attenuated after additional treatments with glutamine metabolism inhibitor BPTES. Additionally, glutamine downregulated miR-143 expression, and miR-143 inactivation alone resulted in enhanced proliferation, migration, and promoted the synthetic phenotype of VSMCs. Moreover, Thy-1 cell surface antigen (THY1) was validated as a downstream target of miR-143, and THY1 expression was upregulated by glutamine in VSMCs. Furthermore, either miR-143 overexpression or THY1 silencing abolished the effect of glutamine on proliferation, migration, and phenotypic switch of VSMCs, supporting a novel glutamine-miR-143-THY1 pathway in modulating VSMC functions. SIGNIFICANCE: This study demonstrated a novel mechanism of glutamine in modulation of VSMC phenotypic switch by targeting miR-143 and THY1, and provides significant insight on targeted therapy of patients with cardiovascular diseases.
Asunto(s)
Regulación de la Expresión Génica , Glutamina/farmacología , MicroARNs/genética , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Antígenos Thy-1/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Humanos , MicroARNs/antagonistas & inhibidores , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Fenotipo , Transducción de Señal , Antígenos Thy-1/genética , Cicatrización de HeridasRESUMEN
BACKGROUND: Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis. METHODS: Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated. RESULTS: Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01-46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25-3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion. CONCLUSIONS: High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.
RESUMEN
This work evaluates solid lipid nanoparticles of thiopental sodium against obesity-induced cardiac dysfunction and hypertrophy and explores the possible mechanism of action. TS loaded SLNs were formulated by hot-homogenization and solvent diffusion method. TS-SLNs were scrutinized for entrapment efficiency, drug loading capacity, gastric stability, particle size, in vitro drug release. Mice were feed with the normal chow or high-fat diet for 08 weeks to induce obesity and primary cardiomyocytes. The therapeutic effects of thiopental sodium in the high fat diet (HFD) induced cardiac hypertrophy. Systolic blood pressure (SBP) was estimated at a regular time interval. At the end of the experimental study, systolic pressure left ventricular, LV end-diastolic pressure and rate of increase of LV pressure and antioxidant, apoptosis, cytokines and inflammatory scrutinized. HFD induced group mice exhibited a reduction in the body weight and enhancement of cardiac hypertrophy marker and dose-dependent treatment of thiopental sodium up-regulation the body weight and down-regulated the cardiac hypertrophy. Thiopental sodium significantly (p < .001) dose-dependently altered the antioxidant, biochemical, cardiac parameters and remodeling. Thiopental sodium significantly (p < .001) dose-dependently reduced the SBP. Thiopental sodium altered the apoptosis marker, pro-inflammatory cytokines, inflammatory parameters along with reduced the p38-MAPK level. The cardiac protective effect of thiopental sodium shed light on future therapeutic interventions in obesity and related cardiovascular complications via inflammatory pathway.
Asunto(s)
Cardiomegalia/tratamiento farmacológico , Cardiomegalia/etiología , Moduladores del GABA/farmacología , Miocitos Cardíacos/efectos de los fármacos , Obesidad/complicaciones , Tiopental/farmacología , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Química Farmacéutica , Dieta Alta en Grasa , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Moduladores del GABA/administración & dosificación , Cardiopatías/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Mediadores de Inflamación/metabolismo , Lípidos/química , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas/química , Estrés Oxidativo , Tamaño de la Partícula , Tiopental/administración & dosificación , Pérdida de Peso/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVE: To construct prokaryotic expression system for expressing, purifying and identifying truncated fragment of extra-cellular segment of sodium pump alpha3 subunit with pGEX-6P-1 GST gene fusion system in Escherichia coli by in-fusion technology. METHODS: According to the conservative sequence of M1-M2 and M3-M4 extra-cellular gene fragments of sodium pump a3 subunit, which published in GenBank, a serial of primers and gene fragments was designed, and directly synthesized to fuse the above two gene fragments. The fusion gene was fused with gene-specific primers by PCR, and then fusion gene fragment was fused into the single stranded homology regions of vector pGEX-6P-1 by in-fusion cloning to construct recombinant vector pGEX-Trf-alpha3 (Truncated fragment of extracellular segment of sodium pump alpha3 subunit, Trf-alpha3). After DH10bac was transferred with it, the pGEX-Trf-alpha3 plasmid was purified and identified by PCR and sequenced. Then the recombinant plasmid pGEX-Trf-alpha3 was expressed in E. coli BL21 cells, inducted by IPTG. GST-Trf-alpha3 fusion protein was purified with Glutathione Sepharose 4B purifying system and analyzed by SDS-PAGE. RESULTS: The results of PCR and sequencing demonstrated that the M1-M2 and M3-M4 extra-cellular gene was inserted in plasmid pGEX-6P-1 vector successfully. And the sequence was correct. Protein sequence analysis showed that the GST-Trf-alpha3 fusion protein was consisted of 262 amino-acid residues. Relative molecular mass in theory was 33.22 X 10(3). The amount of recombinant protein was 10% of the total bacteria protein. The soluble fusion protein was about 80.8%. After affinity purification, the purity of GST-Trf-alpha3 fusion protein was over 95%. There was some extent binding activity between GST-Trf-alpha3 fusion protein and ouabain, but the activity was very low. CONCLUSION: Prokaryotic expression system for expressing truncated fragment of extra-cellular segment of sodium pump alpha3 subunit with pGEX-6P-1 GST gene fusion system in Escherichia coli by in-fusion technology had been constructed. The purified method had also established. High purified GST-Trf-alpha3 fusion protein was obtained. These have found the foundation of further study on its biological function and potential pharmacology function.
Asunto(s)
Escherichia coli/metabolismo , Espacio Extracelular/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Escherichia coli/genética , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Ratones , Datos de Secuencia Molecular , Fragmentos de Péptidos/genética , Plásmidos/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , ATPasa Intercambiadora de Sodio-Potasio/genéticaRESUMEN
In order to explore the activity of a peptide containing rat sodium pump α2 subunit M1-M2 extramembrane fragment (RES2 derivative) in vitro, the peptide (Leu-Ala-Ala-Met-Glu-Asp-Glu-Pro-Ser-Asn-Asp-Asn-Gly-Gly-Gly-Ser) was synthesized by peptide synthesizer with Fmoc method and purified by high performance liquid chromatography (HPLC). Its binding activity was identified by radioligand-receptor binding assay (RRA) and its bioactivity was measured by erythrocyte (86)Rb uptake. The results of saturation binding experiment and competitive binding experiment showed that the synthesized RES2 derivative had the capability to bind to (3)H-ouabain. The dissociation constant (K(d)) was 38.46 nmol/L and IC(50) was 6.353 nmol/L. Erythrocyte (86)Rb uptake experiment showed that the RES2 derivative blocked the inhibitory effect of ouabain on the sodium pump on erythrocyte membrane in a dose-dependent manner. The results showed that the RES2 derivative is capable of binding to ouabain and improving the activity of sodium pump on erythrocyte membrane, suggesting that the RES2 derivative might become an effective antihypertensive drug in the future.
Asunto(s)
Membrana Eritrocítica/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Ouabaína/farmacología , RatasRESUMEN
The purpose of the present study was to elucidate the protective effects of ferulic acid (FA) against cyclophosphamide- (CTX-) induced changes in mice. Forty-eight male ICR mice were divided into four groups. Control group was intraperitoneally (i.p.) injected with 200 µL of phosphate buffer saline (PBS). Model group was intraperitoneally injected with a single dose of CTX (200 mg/kg). FA (50 mg/kg) and FA (100 mg/kg) groups were intraperitoneally injected with a single dose of CTX (200 mg/kg) followed by the intragastric treatment with FA (50, 100 mg/kg) for 7 consecutive days. After 12 d, the mice were sacrificed to analyze the hematological, biochemical, histological parameters and mechanism research. The results indicated that FA significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) in CTX-injected mice. In addition, FA effectively reduced the total numbers of white blood cells (WBCs), red blood cells, platelets, and hemoglobin content. FA also obviously attenuated the histological changes of the heart tissues caused by CTX. Moreover, Western blot demonstrated that FA inhibited the phosphorylations of NF-κB signaling pathway in CTX-stimulated cardiac tissues. In conclusion, FA might be considered as an effective agent in the amelioration of the heart toxicity resulting from CTX treatment.