RESUMEN
OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, and there is an increasing interest in the potential benefits of traditional Chinese medicine, such as Huanglian Jiedu decoction (HJD), for its management. This meta-analysis aimed to determine the efficacy and safety of HJD in the treatment of T2DM. METHODS: A systematic review was conducted across six databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang, from their inception to August 24, 2023. We focused on randomized controlled trials (RCTs) that evaluated HJD as both a monotherapy and in combination treatments for T2DM patients. Data analysis was performed using RevMan 5.3 and Stata 17.0, with evaluations for heterogeneity and publication bias. Additionally, subgroup analyses were stratified based on the duration of treatment. RESULTS: A total of 40 studies involving 3,934 participants were included in the meta-analysis. Both HJD monotherapy and combined with other therapies significantly reduced hemoglobin A1C (HbA1c) fasting blood glucose (FBG) and 2-h postprandial glucose (2hPG) levels, as well as improved insulin resistance. Furthermore, combination therapy enhanced the efficacy rate and favorably altered lipid profiles, including increasing HDL-C and decreasing LDL-C, TC, and TG levels. It was worth noting that the results of the subgroup analysis indicated that, in terms of reducing HbA1c and 2hPG, the efficacy of HJD alone for a duration of less than 3 months was found to be potentially superior to that observed in treatments exceeding 3 months. Adverse event assessment suggested that HJD did not increase the incidence of side effects, including diarrhea, affirming its safety. CONCLUSION: HJD appears to be an effective and safe alternative or adjunctive therapy for T2DM, showing significant improvements in glycemic control and lipid profiles without increasing adverse events. Further rigorous, multicenter RCTs outside China are warranted to validate these findings.
RESUMEN
Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development.
Asunto(s)
Esterasas/metabolismo , Oryza/enzimología , Oryza/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Polen/enzimología , Polen/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Oryza/metabolismo , Peroxisomas/metabolismo , Polen/metabolismoRESUMEN
Large-scale production of male sterile seeds can be achieved by introducing a fertility-restoration gene linked with a pollen-killer gene into a recessive male sterile mutant. We attempted to construct this system in rice by using a late-stage pollen-specific (LSP) promoter driving the expression of maize α-amylase gene ZM-AA1. To obtain such promoters in rice, we conducted comparative RNA-seq analysis of mature pollen with meiosis anther, and compared this with the transcriptomic data of various tissues in the Rice Expression Database, resulting in 269 candidate LSP genes. Initial test of nine LSP genes showed that only the most active OsLSP3 promoter could drive ZM-AA1 to disrupt pollen. We then analyzed an additional 22 LSP genes and found 12 genes stronger than OsLSP3 in late-stage anthers. The promoters of OsLSP5 and OsLSP6 showing higher expression than OsLSP3 at stages 11 and 12 could drive ZM-AA1 to inactivate pollen, while the promoter of OsLSP4 showing higher expression at stage 12 only could not drive ZM-AA1 to disrupt pollen, suggesting that strong promoter activity at stage 11 was critical for pollen inactivation. The strong pollen-specific promoters identified in this study provided valuable tools for genetic engineering of rice male sterile system for hybrid rice production.
Asunto(s)
Oryza/genética , Polen/genética , Regiones Promotoras Genéticas , Fluorescencia , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Proteínas Fluorescentes Verdes/metabolismo , Especificidad de Órganos/genética , Fenotipo , Plantas Modificadas Genéticamente , Reproducibilidad de los Resultados , Transcriptoma/genéticaRESUMEN
Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane-localized legume-lectin receptor kinase that we named OsLecRK-S.7. OsLecRK-S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK-S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376 , Ser378 , Thr386 , Thr403 , and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk-s.7 mutant plant overexpressing OsLecRK-S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK-S.7 was a key regulator of pollen development.
Asunto(s)
Lectinas/metabolismo , Oryza/enzimología , Oryza/fisiología , Polen/enzimología , Polen/crecimiento & desarrollo , Proteínas Quinasas/metabolismo , Membrana Celular/enzimología , Fertilidad , Regulación de la Expresión Génica de las Plantas , Mutación/genética , Oryza/genética , Oryza/ultraestructura , Fenotipo , Filogenia , Polen/genética , Polen/ultraestructura , Proteínas Quinasas/genéticaRESUMEN
BACKGROUND: The mechanisms of atrial fibrillation (AF) induced by obstructive sleep apnea (OSA) are not completely understood. This study investigated the roles of the intrinsic and extrinsic cardiac autonomic nervous system in OSA-induced AF and provided noninvasive autonomic nervous modulation for the suppression of OSA-induced AF by using low-level transcutaneous electrical stimulation (LL-TS) of the auricular branch of the vagus nerve at the tragus. METHODS AND RESULTS: Eighteen dogs received tracheostomy under general anesthesia and were randomly divided into 3 groups: the OSA group (OSA was simulated via clamping of the endotracheal tube at end expiration for 1.5 minutes every 10 minutes, n=6), the LL-TS + OSA group (simulated OSA plus LL-TS, at 80% of the slowing sinus rate, n=6), and the control group (sham surgery without stimulation, n=6). The effective refractory period was significantly shortened after 1 hour of simulated OSA, and the window of vulnerability and plasma norepinephrine levels were both markedly increased in the OSA group. OSA dramatically increased the neural function and activity of the intrinsic and extrinsic cardiac autonomic nervous system, including the superior left ganglionated plexus, the left stellate ganglion, and the left renal sympathetic nerve. OSA also significantly upregulated the expression levels of c-fos and nerve growth factor in the superior left ganglionated plexus and the left stellate ganglion. However, LL-TS markedly improved these parameters. CONCLUSIONS: These findings suggest that the intrinsic and extrinsic cardiac autonomic nervous system plays crucial roles in the acute stage of OSA-induced AF. Noninvasive LL-TS suppressed shortening of atrial refractoriness and autonomic remodeling, which prevented OSA-induced AF.
Asunto(s)
Fibrilación Atrial/etiología , Sistema Nervioso Autónomo/fisiopatología , Frecuencia Cardíaca , Corazón/inervación , Riñón/inervación , Apnea Obstructiva del Sueño/complicaciones , Potenciales de Acción , Animales , Fibrilación Atrial/sangre , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/prevención & control , Sistema Nervioso Autónomo/metabolismo , Biomarcadores/sangre , Modelos Animales de Enfermedad , Perros , Humanos , Masculino , Factor de Crecimiento Nervioso/metabolismo , Norepinefrina/sangre , Proteínas Proto-Oncogénicas c-fos/metabolismo , Periodo Refractario Electrofisiológico , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/terapia , Ganglio Estrellado/metabolismo , Ganglio Estrellado/fisiopatología , Factores de Tiempo , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago/métodosRESUMEN
OBJECTIVES: The aim of this study was to investigate whether low-level tragus stimulation (LL-TS) treatment could reduce myocardial ischemia-reperfusion injury in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The authors' previous studies suggested that LL-TS could reduce the size of myocardial injury induced by ischemia. METHODS: Patients who presented with STEMI within 12 h of symptom onset, treated with primary percutaneous coronary intervention, were randomized to the LL-TS group (n = 47) or the control group (with sham stimulation [n = 48]). LL-TS, 50% lower than the electric current that slowed the sinus rate, was delivered to the right tragus once the patients arrived in the catheterization room and lasted for 2 h after balloon dilatation (reperfusion). All patients were followed for 7 days. The occurrence of reperfusion-related arrhythmia, blood levels of creatine kinase-MB, myoglobin, N-terminal pro-B-type natriuretic peptide and inflammatory markers, and echocardiographic characteristics were evaluated. RESULTS: The incidence of reperfusion-related ventricular arrhythmia during the first 24 h was significantly attenuated by LL-TS. In addition, the area under the curve for creatine kinase-MB and myoglobin over 72 h was smaller in the LL-TS group than the control group. Furthermore, blood levels of inflammatory markers were decreased by LL-TS. Cardiac function, as demonstrated by the level of N-terminal pro-B-type natriuretic peptide, the left ventricular ejection fraction, and the wall motion index, was markedly improved by LL-TS. CONCLUSIONS: LL-TS reduces myocardial ischemia-reperfusion injury in patients with STEMI. This proof-of-concept study raises the possibility that this noninvasive strategy may be used to treat patients with STEMI undergoing primary percutaneous coronary intervention.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Arritmias Cardíacas/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Infarto del Miocardio con Elevación del ST/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Estimulación del Nervio Vago/métodos , Anciano , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Biomarcadores/sangre , China , Forma MB de la Creatina-Quinasa/sangre , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/diagnóstico , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/fisiopatología , Mioglobina/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Prueba de Estudio Conceptual , Estudios Prospectivos , Recuperación de la Función , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/fisiopatología , Volumen Sistólico , Factores de Tiempo , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Resultado del Tratamiento , Estimulación del Nervio Vago/efectos adversos , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Our previous studies showed that renal sympathetic stimulation (RS) may facilitate ischemic ventricular arrhythmia (VA) by increasing left stellate ganglion (LSG) nerve activity, whereas renal sympathetic ablation (RA) may suppress VA. OBJECTIVE: The purpose of this study was to investigate whether renal sympathetic interventions also can affect VA by modulating LSG activity in a cesium-induced long QT canine model. METHODS: Twenty-four dogs were randomly divided into RS group (n = 8), RA group (n = 8), or control group (n = 8). Serum norepinephrine, LSG function, and LSG neural activity were measured before and 3 hours after RS or RA. Increasing doses of cesium chloride then were administered until a "threshold dose" produced sustained ventricular tachycardia or ventricular fibrillation. Early afterdepolarization amplitude, VA prevalence, and tachycardia threshold dose were compared among these groups. Nerve growth factor and c-fos protein expressed in the LSG also were examined. RESULTS: Serum norepinephrine, LSG function, and LSG neural activity were all significantly increased after 3 hours of RS and all were decreased 3 hours after RA. In addition, RS significantly decreased the tachycardia threshold dose, increased the early afterdepolarization amplitude, facilitated the incidence of VAs, and increased the expression of nerve growth factor and c-fos protein. In contrast, RA induced the opposite effects. CONCLUSION: RS promotes, whereas RA suppresses, the incidence of VAs in a canine model of cesium-induced long QT. Modulation of LSG neural activity by RS and RA may be responsible for these different effects.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Ablación por Catéter/métodos , Terapia por Estimulación Eléctrica/métodos , Electrocardiografía , Frecuencia Cardíaca/fisiología , Riñón/inervación , Taquicardia Ventricular/terapia , Animales , Sistema Nervioso Autónomo/cirugía , Cesio/toxicidad , Modelos Animales de Enfermedad , Perros , Masculino , Ganglio Estrellado/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/cirugía , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/fisiopatologíaRESUMEN
Noninvasive magnetic stimulation has been widely used in autonomic disorders in the past few decades, but few studies has been done in cardiac diseases. Recently, studies showed that low-frequency electromagnetic field (LF-EMF) might suppress atrial fibrillation by mediating the cardiac autonomic nervous system. In the present study, the effect of LF-EMF stimulation of left stellate ganglion (LSG) on LSG neural activity and ventricular arrhythmia has been studied in an acute myocardium infarction canine model. It is shown that LF-EMF stimulation leads to a reduction both in the neural activity of LSG and in the incidence of ventricular arrhythmia. The obtained results suggested that inhibition of the LSG neural activity might be the causal of the reduction of ventricular arrhythmia since previous studies have shown that LSG hyperactivity may facilitate the incidence of ventricular arrhythmia. LF-EMF stimulation might be a novel noninvasive substitute for the existing implant device-based electrical stimulation or sympathectomy in the treatment of cardiac disorders.
Asunto(s)
Fibrilación Atrial/terapia , Magnetoterapia/métodos , Infarto del Miocardio/complicaciones , Ganglio Estrellado/fisiopatología , Animales , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Fibrilación Atrial/fisiopatología , Modelos Animales de Enfermedad , Perros , Incidencia , Infarto del Miocardio/fisiopatología , Resultado del TratamientoRESUMEN
OBJECTIVE: To study the protective effects of nerve growth factor (NGF) and Danshen on hippocampal neurons in gerbils (Meriones unguiculatus) with global ischemia-reperfusion injury. METHODS: Global ischemia-reperfusion model was established in 54 male Z:ZCLA gerbils by occlusion of the bilateral carotid arteries. The animal models were randomized into 3 groups to receive treatment with normal saline, NGF, and Danshen 30 min after the reperfusion. At 6 h, 3 and 7 days after the reperfusion, the survival of the hippocampal CA1 pyramidal neurons was observed using optical and electron microscopy, and immunohistochemistry was employed to detect the expressions of Bcl-2 and Bax in the neurons. RESULTS: Neuronal apoptosis was not observed in the hippocampus 6 h after the reperfusion, but at 3 and 7 days, the number of apoptotic neurons increased significantly in the CA1 region. Compared with normal saline, treatments with NGF and Danshen both significantly reduced the number of apoptotic neurons at 3 and 7 days. The number of apoptotic neurons showed no significant difference between NGF and Danshen treatment groups at 3 days, but at 7 days, the apoptotic cell number was significantly lower in NGF group (P<0.05). Bcl-2 expression was the highest in NGF group, and its highest expression occurred at 6 h after the reperfusion; Bax expression was detected in saline group, and underwent no significant changes with the passage of time. CONCLUSION: Both NGF and Danshen show protective effects against global ischemia-reperfusion injury. NGF has a stronger protective effect than Danshen, and this finding provides experimental evidence for selecting appropriate protective agents in the treatment of ischemic brain damage.