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Glucose disturbances are a common comorbidity of major depressive disorder (MDD) patients and have been extensively studied in the past. However, few studies have explored glucose disturbances in first-episode drug-naïve (FEDN) MDD patients. The purpose of this study was to examine the prevalence and risk factors of glucose disturbances in FEDN MDD patients to understand the relationship between MDD and glucose disturbances in the acute early phase and provide important implications for therapeutic interventions. Using a cross-sectional design, we recruited a total of 1718 MDD patients. We collected their socio-demographic information, clinical data, and blood glucose indicators.17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, psychotic symptoms, respectively. The prevalence of glucose disturbances in FEDN MDD patients was 13.6%. Depression, anxiety and psychotic symptoms, body mass index (BMI) levels and suicide attempts rates were higher in the group with glucose disorders than in the group without glucose disorders among patients with first-episode drug-naive MDD. Correlation analysis showed that glucose disturbances were associated with HAMD score, HAMA score, BMI, psychotic symptoms and suicide attempts. Furthermore, binary logistic regression showed that HAMD score and suicide attempts were independently associated with glucose disturbances in MDD patients. Our findings suggest that the prevalence of comorbid glucose disturbances is very high in FEDN MDD patients. Moreover, more severe depressive symptoms and higher suicide attempts are correlated with glucose disturbances in MDD FEDN patients in the early stage.
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Trastorno Depresivo Mayor , Humanos , Prevalencia , Glucosa , Estudios Transversales , Factores de Riesgo , China/epidemiologíaRESUMEN
This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/etiología , Colesterol , Pueblos del Este de Asia , Estudios Retrospectivos , Resultado del Tratamiento , AncianoRESUMEN
Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR.
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Estenosis de la Válvula Aórtica , Valvuloplastia con Balón , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Valvuloplastia con Balón/efectos adversos , Humanos , Diseño de Prótesis , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.
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Cardiomegalia/genética , Proteína p300 Asociada a E1A/genética , Metiltransferasas/genética , Miocitos Cardíacos/metabolismo , Ubiquitina Tiolesterasa/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Angiotensina II/administración & dosificación , Animales , Animales Recién Nacidos , Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Cardiomegalia/patología , Proteína p300 Asociada a E1A/metabolismo , Regulación de la Expresión Génica , Masculino , Metiltransferasas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/citología , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Ubiquitina Tiolesterasa/metabolismo , UbiquitinaciónRESUMEN
Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg-1·d-1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.
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Metformina , Traumatismos de la Médula Espinal , Animales , Axones/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Microglía , Vaina de Mielina/metabolismo , Regeneración Nerviosa , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
The clinical use indications for transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) have expanded from patients at high surgical risk to those at low risk based on the results of multiple large-scale randomized trials. However, patients with bicuspid AS have traditionally been excluded from clinical trials due to their unfavorable morphological characteristics. Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, occurring in 1% to 2% of the total population and affects more than 20% of octogenarians undergoing isolated aortic valve replacement for AS. In recent years, TAVR in patients with bicuspid AS has been the focus of research, especially with respect to the standard of prosthesis size selection. Annulus-based prosthesis size selection using computed tomography (CT) is the standard sizing strategy for tricuspid AS, but no standard sizing for bicuspid AS has been developed thus far. According to Western TAVR experiences, transcatheter heart valve (THV) size selection for BAV patients should be based on the annular structure assessment by CT measurement, whereas Chinese experiences favor adopting the supra-annulus structure assessment for THV size selection. This article will review annular and supra-annular sizing for prosthesis size selection in patients with bicuspid AS before TAVR and discuss which has more favorable clinical outcomes.
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Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Humanos , Tomografía Computarizada Multidetector , Diseño de Prótesis , Resultado del TratamientoRESUMEN
DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.
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Benzofuranos/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Disfunción Cognitiva/etiología , Dendritas/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Hipocampo/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Células PC12 , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Sinapsis/efectos de los fármacosRESUMEN
Objectives: This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. Methods: The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for three years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. Results: In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, P < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Conclusions: Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.
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Hipertensión , Amlodipino/farmacología , Amlodipino/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Presión Sanguínea , Quimioterapia Combinada , Humanos , Hipertensión/tratamiento farmacológico , Estudios Retrospectivos , Estaciones del Año , Resultado del TratamientoRESUMEN
BACKGROUND: Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. METHODS: Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. CONCLUSIONS: The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.
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Hipertermia , Proteoma/análisis , Escroto , Espermatozoides/fisiología , Adulto , Animales , Calor , Humanos , Hipertermia/complicaciones , Hipertermia/patología , Hipertermia/fisiopatología , Infertilidad Masculina/etiología , Infertilidad Masculina/metabolismo , Infertilidad Masculina/fisiopatología , Masculino , Ratones , Ratones Endogámicos ICR , Persona de Mediana Edad , Proteoma/metabolismo , Proteómica/métodos , Escroto/fisiología , Análisis de Semen , Espermatozoides/metabolismo , Testículo/metabolismo , Adulto JovenRESUMEN
BACKGROUND: The Qinghai-Tibetan Plateau (QTP) is the world's highest and largest plateau, but the role of its uplift in the evolution of species or biotas still remains poorly known. Toad-headed lizards of the reproductively bimodal genus Phrynocephalus are a clade of agamids, with all viviparous species restricted to the QTP and adjacent regions. The eastern part of the range of the viviparous taxa is occupied by three closely related but taxonomically controversial species, P. guinanensis, P. putjatia and P. vlangalii. Here, we combined genetic (mitochondrial ND4 gene and nine microsatellite loci), morphological (11 mensural and 11 meristic variables), and ecological (nine climatic variables) data to explore possible scenarios that may explain the discordance between genetic and morphological patterns, and to test whether morphological divergence is associated with local adaptation. RESULTS: We found weak genetic differentiation but pronounced morphological divergence, especially between P. guinanensis and P. vlangalii. Genetically, the species boundary was not so clear between any species pair. Morphologically, the species boundary was clear between P. guinanensis and P. vlangalii but not between other two species pairs. Body size and scale characters accounted best for morphological divergence between species. Morphological divergence was related to habitat types that differ climatically. CONCLUSIONS: Our study provides evidence for genetic and morphological divergence among the three closely related viviparous species of Phrynocephalus lizards, and supports the idea that natural selection in spatially heterogeneous environments can lead to population divergence even in the presence of gene flow. Our study supports the hypothesis that the evolutionary divergence between viviparous Phrynocephalus species was a consequence of environmental change after the uplift of the QTP.
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Variación Genética , Lagartos/anatomía & histología , Lagartos/genética , Animales , Teorema de Bayes , China , Clima , ADN Mitocondrial/genética , Femenino , Genética de Población , Geografía , Haplotipos/genética , Masculino , Polimorfismo Genético , Análisis de Componente Principal , Especificidad de la EspecieRESUMEN
BACKGROUND: The oviparity-viviparity transition is a major evolutionary event, likely altering the reproductive process of the organisms involved. Residual yolk, a portion of yolk remaining unutilized at hatching or birth as parental investment in care, has been investigated in many oviparous amniotes but remained largely unknown in viviparous species. Here, we used data from 20 (12 oviparous and 8 viviparous) species of snakes to see if the oviparity-viviparity transition alters the partitioning of yolk in embryonic snakes. We used ANCOVA to test whether offspring size, mass and components at hatching or birth differed between the sexes in each species. We used both ordinary least squares and phylogenetic generalized least squares regressions to test whether relationships between selected pairs of offspring components were significant. We used phylogenetic ANOVA to test whether offspring components differed between oviparous and viviparous species and, more specifically, the hypothesis that viviparous snakes invest more in the yolk as parental investment in embryogenesis to produce more well developed offspring that are larger in linear size. RESULTS: In none of the 20 species was sex a significant source of variation in any offspring component examined. Newborn viviparous snakes on average contained proportionally more water and, after accounting for body dry mass, had larger carcasses but smaller residual yolks than did newly hatched oviparous snakes. The rates at which carcass dry mass (CDM) and fat body dry mass (FDM) increased with residual yolk dry mass (YDM) did not differ between newborn oviparous and viviparous snakes. Neither CDM nor FDM differed between newborn oviparous and viviparous snakes after accounting for YDM. CONCLUSIONS: Our results are not consistent with the hypothesis that the partitioning of yolk between embryonic and post-embryonic stages differs between snakes that differ in parity mode, but instead show that the partitioning of yolk in embryonic snakes is species-specific or phylogenetically related. We conclude that the oviparity-viviparity transition does not alter yolk partitioning in embryonic snakes.
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Yema de Huevo/fisiología , Embrión no Mamífero/fisiología , Oviparidad/fisiología , Serpientes/embriología , Viviparidad de Animales no Mamíferos/fisiología , Animales , Animales Recién Nacidos , Femenino , Filogenia , Análisis de Regresión , Especificidad de la EspecieRESUMEN
Objective To observe the efficacy and safety of Shaoyao Gancao Decoction (SGD) in treating olanzapine induced hyperprolactinemia. Methods Totally 120 schizophrenia patients who took Olanzapine Tablet (OT) were assigned to the treatment group and the control group by random number table, 60 in each group. All patients took OT. Those in the treatment group additionally took SGD. The ther- apeutic course for all was 8 weeks. Serum levels of prolactin were measured before treatment and at the end of week 2, 4, and 8 after treatment. The spiritual symptoms of patients were assessed by Positive and Negative Syndrome Scale (PANSS) before treatment and at the end of week 8 after treatment. Adverse reactions were assessed using Treatment Emergent Symptom Scale (TESS) before treatment and at the end of week 8 after treatment. Results Compared with before treatment in the same group, ser- um levels of prolactin were significantly reduced in the treatment group at the end of week 4 and 8 after treatment (P <0. 05). There was no statistical difference in serum levels of prolactin in the control group among each time points (P > 0. 05). Compared with the control group, serum levels of prolactin de- creased significantly in the treatment group at the end of week 4 and 8 after treatment (P <0. 01). There was no statistical difference in PANSS between the two groups at the end of week 8 after treatment (P> 0. 05). Adverse reactions occurred in 5 cases (943%) of the treatment group and 4 cases (7. 14%) in the control group. They were manifested as insomnia, headache, constipation, and incapability of sitting quietly. There was no statistical difference in adverse reaction between the two groups (P'>0. 05). Con- clusions SGD could effectively improve olanzapine-induced hyperprolactinemia, and had no obvious effect on psychotic symptoms. It showed no obvious adverse reactions.
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Medicamentos Herbarios Chinos , Hiperprolactinemia , Olanzapina , Antipsicóticos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Hiperprolactinemia/inducido químicamente , Hiperprolactinemia/tratamiento farmacológico , Olanzapina/efectos adversos , Prolactina , Esquizofrenia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
The fragmentation reactions of sodiated beta-anilinodidrochalcones have been investigated by electrospray ionization multi-stage mass spectrometry (ESI-MS(n)). The fragment ion of sodiated N-benzylidenebenzenamine (P1) easily undergoes ion-molecule reactions with the residual ESI solvent molecules (H2O and CH3OH) in the vacuum system, as verified by MS3 and accurate MS analysis. The formed hydrated ions appear as an unusual leading peak in the profile spectrum, which results in a deviant decreasing mass shift of almost 1 Da. Density functional theory calculations indicate that P1 easily associates with H2O without any energy barrier. Thus, the hydrated P1 exists partially as a loose system of P1 and H2O, which provides a reasonable explanation for the decreasing mass shift of the solvated P1. The above results are important in obtaining structural information from MS(n) spectra and preventing erroneous data interpretation for the analogous adducts.
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In mammals, ovarian follicle is made of an oocyte with its surrounding granulosa cells and theca cells. Follicular growth and development is a highly coordinated programmable process, which guarantees the normal oocyte maturation and makes it having the fertilizing capacity. The paracrine and autocrine between oocytes and granulosa cells are essential for the follicular development to provide a suitable microenvironment. Phosphatidylinositol-3 kinase /protein kinase B is one of these important regulatory signaling pathways during this developmental process, and bone morphogenetic protein-15 an oocyte-specific secreted signal molecule, which regulates the follicular development by paracrine in the mammalian ovary. The present article overviewed the role of phosphatidylinositol-3 kinase / protein kinase B signaling during the follicular development based on our previous investigation about protein kinase B /forkhead transcription factor forkhead family of transcription factors -3a, and then focused on the regulatory effects of bone morphogenetic protein-15, as a downstream signal molecule of phosphatidylinositol-3 kinase / forkhead family of transcription factors -3a pathway, on ovarian follicular development, which helped to further understand the molecular mechanism regulating the follicular development and to treat ovarian diseases like infertility.
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Proteína Morfogenética Ósea 15/fisiología , Folículo Ovárico/crecimiento & desarrollo , Fosfatidilinositol 3-Quinasa/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Animales , Femenino , Células de la Granulosa/fisiología , Humanos , Mamíferos , Ovario/crecimiento & desarrollo , Transducción de SeñalRESUMEN
Increased tau acetylation at K274 and K281 has been observed in the brains of Alzheimer's disease (AD) patients and animal models, and mitochondrial dysfunction are noticeable and early features of AD. However, the effect of acetylated tau on mitochondria has been unclear until now. Here, we constructed three type of tau forms, acetylated tau mutant by mutating its K274/K281 into Glutamine (TauKQ) to mimic disease-associated lysine acetylation, the non-acetylation tau mutant by mutating its K274/K281 into Arginine (TauKR) and the wild-type human full-length tau (TauWT). By overexpression of these tau forms in vivo and in vitro, we found that, TauKQ induced more severe cognitive deficits with neuronal loss, dendritic plasticity damage and mitochondrial dysfunctions than TauWT. Unlike TauWT induced mitochondria fusion, TauKQ not only induced mitochondria fission by decreasing mitofusion proteins, but also inhibited mitochondrial biogenesis via reduction of PGC-1a/Nrf1/Tfam levels. TauKR had no significant difference in the cognitive and mitochondrial abnormalities compared with TauWT. Treatment with BGP-15 rescued impaired learning and memory by attenuation of mitochondrial dysfunction, neuronal loss and dendritic complexity damage, which caused by TauKQ. Our data suggested that, acetylation at K274/281 was an important post translational modification site for tau neurotoxicity, and BGP-15 is a potential therapeutic drug for AD.
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Enfermedad de Alzheimer , Proteínas tau , Animales , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Modelos Animales de Enfermedad , Mitocondrias/metabolismo , Oximas/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismoRESUMEN
Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n = 55) and the control group (n = 101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2â µmol/L in serum creatinine (Scr) from baseline within 72â h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and ß2-microglobulin at 24/48/72â h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P = .043). Compared with the control group, Scr, uric acid, and ß2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P = .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.
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Lesión Renal Aguda , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Nicorandil/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Ácido Úrico/efectos adversos , Estudios Retrospectivos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Resultado del TratamientoRESUMEN
Several epidemiological studies have shown a clear inverse relationship between serum levels of high-density lipoprotein cholesterol (HDL-C) and the risk of atherosclerotic cardiovascular disease (ASCVD), even at low-density lipoprotein cholesterol levels below 70 mg/dL. There is much evidence from basic and clinical studies that higher HDL-C levels are beneficial, whereas lower HDL-C levels are detrimental. Thus, HDL is widely recognized as an essential anti-atherogenic factor that plays a protective role against the development of ASCVD. Percutaneous coronary intervention is an increasingly common treatment choice to improve myocardial perfusion in patients with ASCVD. Although drug-eluting stents have substantially overcome the limitations of conventional bare-metal stents, there are still problems with stent biocompatibility, including delayed re-endothelialization and neoatherosclerosis, which cause stent thrombosis and in-stent restenosis. According to numerous studies, HDL not only protects against the development of atherosclerosis, but also has many anti-inflammatory and vasoprotective properties. Therefore, the use of HDL as a therapeutic target has been met with great interest. Although oral medications have not shown promise, the developed HDL infusions have been tested in clinical trials and have demonstrated viability and reproducibility in increasing the cholesterol efflux capacity and decreasing plasma markers of inflammation. The aim of the present study was to review the effect of HDL on stent biocompatibility in ASCVD patients following implantation and discuss a novel therapeutic direction of HDL infusion therapy that may be a promising candidate as an adjunctive therapy to improve stent biocompatibility following percutaneous coronary intervention.
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Aterosclerosis , Intervención Coronaria Percutánea , Humanos , Lipoproteínas HDL , Reproducibilidad de los Resultados , Stents/efectos adversos , HDL-Colesterol , Aterosclerosis/tratamiento farmacológicoRESUMEN
Long-term studies are especially suited for disentangling the effects of extrinsic and intrinsic factors on both total reproductive investment and reproductive allocation in offspring number versus offspring size. Female reproductive traits of the red-banded wolf snake (Lycodon rufozonatus) from Zhejiang, East China were studied in four years between 1999 and 2014. Egg-laying dates overall extended from late June to late July, and varied among years. Postpartum body mass, clutch size, clutch mass, and egg size were positively related to female size (snout vent length, SVL) in each year. Postpartum body mass, clutch mass, and egg size differed among years after accounting for female SVL, whereas clutch size did not. Setting female SVL at the same level, postpartum body mass was greater in 2010 than in 2014, clutch mass was greater in 2010 than in 2011 and 2014, and egg size was greater in 2010 than in the other three years. Females did not trade off egg size against number. Egg size was positively related to postpartum body condition in each year. Females laid larger eggs in 2010 than in other three years after removing the influence of maternal body condition. Our study provides evidence for the traditional view that reproductive output is highly linked to maternal body size in snakes, but not following Smith and Fretwell's (1974) classic prediction that females with different amounts of resources to invest in reproduction should give priority to adjusting the number rather than size of their offspring. Maternal body size and condition both are important sources of variation in egg size, but factors other than these two variables may also affect the size of eggs produced by female L. rufozonatus.
RESUMEN
Background Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double-blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results A total of 238 patients with ST-segment-elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6-mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g; P=0.022), and the effect remained significant on long-term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g; P=0.008). The incidence of no-reflow/slow-flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118]; P=0.001), and thus, complete ST-segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118]; P=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%; P=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%; P=0.009) after reperfusion. Conclusions In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST-segment-elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03445728.
Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Nicorandil/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/terapia , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
Spectral characteristics and the magnitudes of light absorption by suspended particulate matter were determined by spectrophotometry in this optically complex Lake Chagan waters for the purpose of surveying the natural variability of the absorption coefficients to parameterize the bio-optical models for converting satellite or in-situ water reflectance signatures into water quality information. Experiments were carried out on seasonal frozen Lake Chagan, one representative inland case-2 water body in Northeast of China. Particulate absorption properties analyzed using the field data on July 15th and October 12th 2009 were measured using the quantitative filter technique to produce absorption spectra containing several fractions that could be attributed to two main optical active constituents (OACs) phytoplankton pigments and non-algal particulates (mineral sediments, and organic detritus). Results suggested that the suspended particulate matter (SPM) concentration was higher while phytoplankton biomass (chlorophyll-a concentration) was lower in July and that in October. The spectral shape of total suspended particulate matter resembled that of non-algal particulates which contributed greater than phytoplankton in total particulate absorption during both periods. An obvious absorption peak occurring at around 440 nm exhibited an increase in phytoplankton contribution in October. Non-algal particulate absorption at 440 nm (a(NAP) (440)) had better correlation with total suspended particulate matter concentration than that with chlorophyll-a over the two periods. Light absorption by phytoplankton pigments in the Chagan lake region was generally lower than that of non-algal components. Chl. a dominating phytoplankton pigment composition functioned exponentially with its absorption coefficients at 440 and 675 nm specifically, the average values of which in July were 0.146 8 m2 x mg(-1) and 0.050 3 respectively while in October they were 0.153 3 and 0.013 2 m2 x mg(-1) varying regionally and seasonally due to the changes in specific composition, light and nutrient conditions.