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BACKGROUND AND OBJECTIVES: Long-term pathological myocardial hypertrophy (MH) seriously affects the normal function of the heart. Dronedarone was reported to attenuate left ventricular hypertrophy of mice. However, the molecular regulatory mechanism of dronedarone in MH is unclear. METHODS: Angiotensin II (Ang II) was used to induce cell hypertrophy of H9C2 cells. Transverse aortic constriction (TAC) surgery was performed to establish a rat model of MH. Cell size was evaluated using crystal violet staining and rhodamine phalloidin staining. Reverse transcription quantitative polymerase chain reaction and western blot were performed to detect the mRNA and protein expressions of genes. JASPAR and luciferase activity were conducted to predict and validate interaction between forkhead box O3 (FOXO3) and protein kinase inhibitor alpha (PKIA) promoter. RESULTS: Ang II treatment induced cell hypertrophy and inhibited sirtuin 1 (SIRT1) expression, which were reversed by dronedarone. SIRT1 overexpression or PKIA overexpression enhanced dronedarone-mediated suppression of cell hypertrophy in Ang II-induced H9C2 cells. Mechanistically, SIRT1 elevated FOXO3 expression through SIRT1-mediated deacetylation of FOXO3 and FOXO3 upregulated PKIA expression through interacting with PKIA promoter. Moreover, SIRT1 silencing compromised dronedarone-mediated suppression of cell hypertrophy, while PKIA upregulation abolished the influences of SIRT1 silencing. More importantly, dronedarone improved TAC surgery-induced MH and impairment of cardiac function of rats via affecting SIRT1/FOXO3/PKIA axis. CONCLUSIONS: Dronedarone alleviated MH through mediating SIRT1/FOXO3/PKIA axis, which provide more evidences for dronedarone against MH.
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Correction for 'Noncovalent wedging effect catalyzed the cis to syn transformation of a surface-adsorbed polymer backbone toward an unusual thermodynamically stable supramolecular product' by Zhi-Xuan Liu et al., Phys. Chem. Chem. Phys., 2022, 24, 30010-30016, https://doi.org/10.1039/D2CP04184G.
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Brown planthopper (BPH, Nilaparvata lugens), a highly destructive insect pest, poses a serious threat to rice (Oryza sativa) production worldwide. Jasmonates are key phytohormones that regulate plant defences against BPH; however, the molecular link between jasmonates and BPH responses in rice remains largely unknown. Here, we discovered a Poaceae-specific metabolite, mixed-linkage ß-1,3;1,4-d-glucan (MLG), which contributes to jasmonate-mediated BPH resistance. MLG levels in rice significantly increased upon BPH attack. Overexpressing OsCslF6, which encodes a glucan synthase that catalyses MLG biosynthesis, significantly enhanced BPH resistance and cell wall thickness in vascular bundles, whereas knockout of OsCslF6 reduced BPH resistance and vascular wall thickness. OsMYC2, a master transcription factor of jasmonate signalling, directly controlled the upregulation of OsCslF6 in response to BPH feeding. The AT-rich domain of the OsCslF6 promoter varies in rice varieties from different locations and natural variants in this domain were associated with BPH resistance. MLG-derived oligosaccharides bound to the plasma membrane-anchored LECTIN RECEPTOR KINASE1 OsLecRK1 and modulated its activity. Thus, our findings suggest that the OsMYC2-OsCslF6 module regulates pest resistance by modulating MLG production to enhance vascular wall thickness and OsLecRK1-mediated defence signalling during rice-BPH interactions.
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Hemípteros , Oryza , Animales , Glucanos/metabolismo , Oryza/genética , Oryza/metabolismo , PoaceaeRESUMEN
The significant influence of noncovalent interactions on catalytic processes has been recently appreciated but is still in its infancy. In this report, it is found that wedging Me-PTCDI (small-molecule) between the alkyl chains of PffBT4T-2OD (polymer) and a graphite substrate can reduce the energy barrier of flipping over the surface-adsorbed alkylthiophene group from the cis to syn conformation, revealing the catalytic role of Me-PTCDI via a noncovalent wedging effect. The wedging of Me-PTCDI brings the interactions between the alkyl chains and substrate to a very weak level by lifting up the alkyl chains, which eliminates the major hindrance of the flipping process to one main factor: the torsion of the dihedral angles of the thiophene group. The Me-PTCDI/syn PffBT4T-2OD arrangement shows unusual stability compared to the cis one because the syn conformation allows the alkyl chains to construct dense lamella and facilitates interactions between Me-PTCDI and the syn PffBT4T-2OD backbones. The results are helpful for boosting the development of noncovalent catalysis and bottom-up fabrications toward devices functionalized at a molecular level.
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Hypoxia frequently occurs in aquatic environments, especially in aquaculture areas. However, research on the relationship between hypoxic aquatic environments with viral diseases outbreak is limited, and its underlying mechanisms remain elusive. Herein, we demonstrated that hypoxia directly triggers the outbreak of infectious spleen and kidney necrosis virus (ISKNV) disease. Hypoxia or activated hypoxia-inducible factor (HIF) pathway could remarkably increase the levels of viral genomic DNA, titers, and gene expression, indicating that ISKNV can response to hypoxia and HIF pathway. To reveal the mechanism of ISKNV respond to HIF pathway, we identified the viral hypoxia response elements (HREs) in ISKNV genome. Fifteen viral HREs were identified, and four related viral genes responded to the HIF pathway, in which the hre-orf077r promoter remarkably responded to the HIF pathway. The level of orf077r mRNA dramatically increased after the infected cells were treated with dimethyloxalylglycine (DMOG) or the infected cells/fish subjected to hypoxic conditions, and overexpressed orf077r could remarkably increase the ISKNV replication. These finding shows that hypoxic aquatic environments induce the expression of viral genes through the viral HREs to promote ISKNV replication, indicating that viral HREs might be important biomarkers for the evaluation of the sensitivity of aquatic animal viral response to hypoxia stress. Furthermore, the frequencies of viral HREs in 43 species aquatic viral genomes from 16 families were predicted and the results indicate that some aquatic animal viruses, such as Picornavirdea, Dicistronviridae, and Herpesviridae, may have a high risk to outbreak when the aquatic environment encounters hypoxic stress.
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Enfermedades de los Peces , Iridoviridae , Animales , ADN Viral , Enfermedades de los Peces/epidemiología , Enfermedades de los Peces/genética , Humanos , Hipoxia/genética , Iridoviridae/genética , Elementos de RespuestaRESUMEN
OBJECTIVE: To explore the changes in plasma angiotensin II (Ang II) and circadian rhythm of blood pressure among hypertensive patients with sleep apnea syndrome (SAS) before and after continuous positive airway pressure (CPAP) or surgical treatment. METHODS: A total of 180 essential hypertension patients were enrolled in our study. The determination of plasma Ang II concentration, ambulatory blood pressure (ABP), and polysomnography (PSG) monitoring were performed before and 3 months after CPAP or surgical treatment. RESULTS: Patients were classified into three groups by their apnea-hypopnea index (AHI): essential hypertension group (EH group, n = 72; AHI< 5), essential hypertension with mild SAS group (EH+mild SAS group, n = 60, 5 ≤ AHI < 20), and essential hypertension with moderate and severe SAS group (EH + moderate-severe SAS group, n = 48, AHI ≥ 20). The concentrations of plasma Ang2 in the above three groups were 13.42 ± 3.27, 16.17 ± 3.82, and 18.73 ± 4.05 ng/mL respectively before treatment, and Ang2 concentration in EH patients combined with SAS was significantly higher than that in EH group (all P < 0.05). After treatment the values in the latter two groups significantly decreased to 14.67 ± 2.56 and 15.03 ± 3.41 ng/mL respectively (P < 0.05). The incidence of non-dipper blood pressure curve in EH patients was 31.9%, and those in hypertensive patients with mild SAS and moderate-severe SAS were 51.7% and 58.3%, respectively before treatment. The incidence of non-dipper blood pressure curve in the EH patients with mild SAS was significantly higher than that of patients with EH alone (P < 0.05). After CPAP treatment or surgery, the incidence of non-dipper blood pressure curve in the two SAS groups was significantly decreased to 38.3% and 39.6%, respectively (P < 0.05). CONCLUSIONS: Ang II might play a role in blood pressure variability in patients with obstructive SAS. CPAP or surgical treatment can improve blood pressure disorder and decrease plasma Ang II level in patients with obstructive SAS.
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Angiotensina II/sangre , Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Hipertensión/fisiopatología , Síndromes de la Apnea del Sueño/sangre , Síndromes de la Apnea del Sueño/terapia , Adulto , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Masculino , Persona de Mediana Edad , Faringe/cirugía , Polisomnografía , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/cirugíaRESUMEN
OBJECTIVE: To investigate the change of circadian blood pressure variability (BPV) and plasma neopterin before and after surgery (uvulopalatopharyngoplasty) for patients with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 382 OSAS patients underwent uvulopalatopharyngoplasty were divided into three groups based on polysomnography (PSG) results: mild OSAS (n = 206), moderate OSAS (n = 108) and severe OSAS (n = 68). Plasma neopterin, 24-hour ambulatory blood pressure monitoring (ABPM), PSG were measured before and 3 months after surgery. RESULTS: Plasma neopterin increased in proportion to severity of OSAS before surgery (15.08 nmol/L, 27.68 nmol/L and 37.32 nmol/L in patients with mild to severe OSAS) which were significantly reduced post surgery (9.92 ng/ml, 15.07 ng/ml and 18.54 ng/ml, all P < 0.05 vs. pre-surgery). The incidence of non-dipper curve in three OSAS groups were 50.2%, 72.7% and 86.5%, respectively before surgery and the values decreased to 34.8%, 48.2% and 49.2% after surgery (all P < 0.05 vs. pre-surgery). Relevance analysis indicates that D-value of nocturnal and diurnal blood pressure was negatively correlated with plasma neopterin. CONCLUSION: Our findings indicated that plasma neopterin and the incidence of non-dipper could reliably reflect OSAS severity and could thus be used to evaluate the surgery efficacy. Plasma neopterin might be an important player in the pathophysiology of OSAS via modulating blood pressure variability.
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Presión Sanguínea , Neopterin/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/cirugía , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Ritmo Circadiano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos OtorrinolaringológicosRESUMEN
OBJECTIVE: To introduce the treatment of severe obstructive sleep apnea-hypopnea syndrome (OSAHS) with Repose bone screw system and to evaluate the treating effect. METHODS: Thirty-two patients with severe OSAHS (Friedman classification II, III) were treated with tongue ablation + uvulopalatopharyngoplasty + hard palate shortening + Repose suspension. All patients were followed-up for 6 months. Apnea hypopnea index (AHI), lowest oxygen percent saturation (LSaO2), body mass index (BMI), vallecula epiglottic-lateral pharyngeal wall (V-LPW) and pharyngeal airway space (PAS) were used for the diagnosis and evaluation. RESULTS: The AHI in 32 patients reduced from (78.3 +/- 11.6)/h to (18.4 +/- 12.5)/h (x(-) +/- s), t = 13.5, P = 0.000. The LSaO2 increased from (0.632 +/- 0.007) to (0.794 +/- 0.006), t = 4.1, P = 0.000. The BMI was statistical indiscriminate. The V-LPW increased from (12.1 +/- 3.2) mm to (16.9 +/- 2.6) mm (t = 2.5, P = 0.014). PAS increased from (9.2 +/- 3.3) mm to (15.6 +/- 2.4) mm (t = 7.6, P = 0.000). The total effective rate was 93.8%. Three genioglossus stabilization patients complained about foreign body sensation in the mouth floor 3 - 7 days after procedures, which disappeared in 6 months. One genioglossus stabilization patients complained about mandibular osteomyelitis 3 months after procedures, which recovered after anti-inflammatory treatment for 5 days. One genioglossus stabilization patients appeared hypoglossia bleeding, which stopped after compression. One hyoid suspension patients showed haematoma of submandibular region and cured after incision and drainage. CONCLUSION: Repose system was an effective method, safe, simple, with few complications.