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1.
Neurosci Bull ; 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34633650

RESUMEN

Parkinson's disease (PD) is the second most common and fastest-growing neurodegenerative disorder. In recent years, it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis. However, little is known about whether and how the caudal zona incerta (ZIc) regulates parkinsonian motor symptoms. Here, we showed that specific glutamatergic but not GABAergic ZIcVgluT2 neurons regulated these symptoms. ZIcVgluT2 neuronal activation induced time-locked parkinsonian motor symptoms. In mouse models of PD, the ZIcVgluT2 neurons were hyperactive and inhibition of their activity ameliorated the motor deficits. ZIcVgluT2 neurons monosynaptically projected to the substantia nigra pars reticulata. Incerta-nigral circuit activation induced parkinsonian motor symptoms. Together, our findings provide a direct link between the ZIc, its glutamatergic neurons, and parkinsonian motor symptoms for the first time, help to better understand the mechanisms of PD, and supply a new important potential therapeutic target for PD.

2.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3177-3184, 2021 Sep.
Artículo en Chino | MEDLINE | ID: mdl-34658203

RESUMEN

Ecological security is an important guarantee for the sustainable development of regional economy and society. We analyzed the change characteristics of fraction vegetation coverage (FVC) and remote sensing ecological index (RSEI) of four irrigated agriculture regions of the Loess Plateau (Yinchuan Plain, Hetao Plain, Fenhe River Valley and Weihe River Plain) based on the remote sensing data from 2000 to 2018. The results showed that the FVC decreased in the study area from 2000 to 2018. The variation trend of FVC differed among the four irrigated agricultural distribution areas. The RSEI of the whole area showed an overall downward trend, the RSEI of Yinchuan Plain (down 0.06) and Weihe River Plain (down 0.07) decreased significantly, and the RSEI of Hetao Plain remained stable. The RSEI of Fenhe River Valley showed an increased trend. The ecological stability of Yinchuan Plain and Fenhe River Valley was relatively low, the ecological environment of Hetao Plain was relatively stable, and the ecological environment of Weihe River Plain continued to degrade. The results were important for regional ecological environment protection and agricultural sustainable development.


Asunto(s)
Ecosistema , Tecnología de Sensores Remotos , Agricultura , Ríos , Desarrollo Sostenible
3.
Chem Biodivers ; 18(10): e2100512, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34347345

RESUMEN

Two new phenol derivatives, namely insphenol A (1) and acetylpeniciphenol (2), along with seven known analogs (3-9), were isolated from the deep-sea cold seep-derived fungus, Aspergillus insuetus SD-512. The structures of 1 and 2 were established by extensive interpretation of NMR and mass spectroscopic data. The absolute configuration of 1 was determined by the combination of coupling constant analysis and acid hydrolysis. Among the isolated compounds, insphenol A (1) represents the first example of isopentenyl phenol derivative with a unique 1-glycosylation from the species Aspergillus insuetus. The isolated new compounds were evaluated for antibacterial activities against six human or aquatic pathogens, while compound 2 exhibited inhibitory effect against Edwardsiella tarda, Vibrio alginolyticus, and V. vulnificus, with MIC values of 4, 8, and 8 µg/mL, respectively.

4.
World J Clin Cases ; 9(22): 6319-6328, 2021 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-34434998

RESUMEN

BACKGROUND: Little is known about the postoperative sleep quality of infective endocarditis patients during hospitalization and after discharge. AIM: To investigate the sleep characteristics of infective endocarditis patients and to identify potential risk factors for disturbed sleep quality after surgery. METHODS: The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale were used to assess patient sleep quality. Logistic regression was used to explore the potential risk factors. RESULTS: The study population (n = 139) had an average age of 43.40 ± 14.56 years, and 67.6% were men (n = 94). Disturbed sleep quality was observed in 86 patients (61.9%) during hospitalization and remained in 46 patients (33.1%) at 6 mo after surgery. However, both PSQI and Epworth Sleepiness Scale scores showed significant improvements at 6 mo (P < 0.001 and P = 0.001, respectively). Multivariable logistic regression analysis showed that the potential risk factors were age (odds ratio = 1.125, 95% confidence interval: 1.068-1.186) and PSQI assessed during hospitalization (odds ratio = 1.759, 95% confidence interval: 1.436-2.155). The same analysis in patients with PSQI ≥ 8 during hospitalization suggested that not using sleep medication (odds ratio = 15.893, 95% confidence interval: 2.385-105.889) may be another risk factor. CONCLUSION: The incidence of disturbed sleep after infective endocarditis surgery is high. However, the situation improves significantly over time. Age and early postoperative high PSQI score are risk factors for disturbed sleep quality at 6 mo after surgery.

5.
World J Stem Cells ; 13(7): 894-913, 2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34367483

RESUMEN

Stem cell transplantation is an appealing potential therapy for vascular diseases and an indispensable key step in vascular tissue engineering. Substantial effort has been made to differentiate stem cells toward vascular cell phenotypes, including endothelial cells (ECs) and smooth muscle cells. The microenvironment of vascular cells not only contains biochemical factors that influence differentiation but also exerts hemodynamic forces, such as shear stress and cyclic strain. More recently, studies have shown that shear stress can influence the differentiation of stem cells toward ECs. A deep understanding of the responses and underlying mechanisms involved in this process is essential for clinical translation. This review highlights current data supporting the role of shear stress in stem cell differentiation into ECs. Potential mechanisms and signaling cascades for transducing shear stress into a biological signal are proposed. Further study of stem cell responses to shear stress will be necessary to apply stem cells for pharmacological applications and cardiovascular implants in the realm of regenerative medicine.

6.
Med Sci Monit ; 27: e930596, 2021 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-34433799

RESUMEN

BACKGROUND The aim of this study was to measure sleep quality among patients who underwent infective endocarditis (IE) surgery and identify the risk factors involved in sleep disorders. MATERIAL AND METHODS In this study, we used actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleep Scale (ESS) to determine the clinical characteristics of sleep disorders in 116 patients with IE who were in rehabilitation after surgery. RESULTS Our results showed that 46 (39.7%) patients had sleep efficiency over 85%, while 70 (60.3%) patients had sleep efficiency below 85%. The correlation analysis showed that sleep efficiency was related to the duration of the disease, with a longer duration leading to lower sleep efficiency (P=0.031). The sleep efficiency of patients with IE following surgery was also affected by alcohol consumption; however, surprisingly, patients with "heavy" alcohol consumption had higher sleep efficiency (P=0.030). We found a significant correlation between sleep efficiency and postoperative interleukin-6 (IL) levels, C-reactive protein (CRP) levels, and preoperative erythrocyte sedimentation rate (P<0.05). No significant correlation was found between brain natriuretic peptide levels and sleep efficiency, PSQI score, or ESS score. Postoperative hemoglobin (Hb) level was associated with sleep efficiency (R=0.194, P=0.036), but there was no statistically significant correlation between the PSQI and ESS scores. Postoperative alanine transaminase (ALT) showed a significant negative correlation with sleep efficiency (R=-0.27, P=0.003). CONCLUSIONS We found a high prevalence of sleep disorders in patients with IE along with an increase in inflammatory factors, including postoperative IL-6, CRP, ALT, and Hb levels.


Asunto(s)
Válvula Aórtica/cirugía , Cateterismo Cardíaco/efectos adversos , Endocarditis/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Complicaciones Posoperatorias/patología , Trastornos del Sueño-Vigilia/patología , Adulto , Válvula Aórtica/lesiones , Endocarditis/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Complicaciones Posoperatorias/etiología , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Trastornos del Sueño-Vigilia/etiología , Encuestas y Cuestionarios
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 500-507, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812421

RESUMEN

OBJECTIVE: To investigate the effect of autophagy on the drug resistance of different human lymphoma cells. METHODS: Human Burkitt's lymphoma cell Daudi, human B lymphoma cell SUDHL-4, and human mantle cell lymphoma cell JeKo-1 were taken as the research subjects. The expression of Atg5 was inhibited by the treatments of autophagy inhibitors or stable interference via lentivirus infection. The autophagy activity of B lymphoma cell was changed, and the changes of lymphoma cells to the drug resistance of ADR and VCR was observed. RESULTS: JeKo-1 cells showed the strongest resistance to ADR and VCR, followed by SUDHL-4, and Daudi cells showed the weakest resistance to ADR and VCR. At the same time, JeKo-1 cells showed the strongest autophagy activity, followed by SUDHL-4, and Daudi cells showed the weakest autophagy activity. After the treatments of autophagy inhibitors or stable Atg5 interference, the resistance of lymphoma cells to ADR and VCR was significantly weakened, and there was the positive correlation at the drug resistance and the autophagy activity of B lymphoma cell. CONCLUSION: The higher autophagy activity in lymphoma cells, the lower chemotherapy resistance of the lymphoma cells after autophagy was inhibited.


Asunto(s)
Linfoma de Burkitt , Linfoma de Células B , Adulto , Autofagia , Línea Celular Tumoral , Resistencia a Medicamentos , Humanos
9.
Bioorg Chem ; 110: 104822, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33770672

RESUMEN

Thirteen alkaloids, which include three new diketopiperazines, namely, 3-hydroxyprotuboxepin K (4), 3,15-dehydroprotuboxepin K (5), and versiamide A (6), together with ten known alkaloid derivatives (1-3 and 7-13), were isolated from the marine red algal-derived fungus Aspergillus creber EN-602. Versiamide A (6) represents the first example of a naturally occurring quinazolinone alkaloid with a diketopiperazine ring that is derived from phenylalanine (Phe) and leucine (Leu). The structures of these compounds were elucidated by detailed interpretation of their 1D/2D NMR spectroscopic and mass spectrometric data, while the absolute configurations of compounds 1-6 were established on the basis of X-ray crystallographic analysis and time-dependent density functional (TDDFT) calculations of the ECD spectra. Compounds 1, 2, and 4 exhibited inhibitory activity against the angiotensin converting enzyme (ACE) with IC50 values of 11.2, 16.0, and 22.4 µM, respectively, and compounds 5 and 6 inhibited various aquatic bacteria with MIC values that ranged from 8 to 64 µg/mL. The intermolecular interactions and potential binding sites between compounds 1-6 and ACE were investigated via molecular docking simulations.


Asunto(s)
Alcaloides/farmacología , Aspergillus/química , Inhibidores Enzimáticos/farmacología , Peptidil-Dipeptidasa A/metabolismo , Rhodophyta/microbiología , Alcaloides/biosíntesis , Alcaloides/química , Aspergillus/metabolismo , Cristalografía por Rayos X , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad
10.
Antibiotics (Basel) ; 10(2)2021 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-33672705

RESUMEN

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I-M (1-5), which have diverse substitution patterns, and seven known related analogues (6-12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1-3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7ß-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

11.
Huan Jing Ke Xue ; 42(2): 891-899, 2021 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-33742884

RESUMEN

Focusing on low biogas yields in the anaerobic co-digestion of waste activated sludge and food waste, the enhancing effects and mechanisms of microscale zero valent iron (mZVI) on anaerobic co-digestion was investigated. The results indicated that the addition of mZVI enhanced the methanogenesis stage of co-digestion but had no significant effect on the solubilization, hydrolysis, and acidification stages. With a dosage of 10 g·L-1 mZVI, the cumulative methane yield (based on VS) within 15 days reached 238.68 mL·g-1, which was 20.05% higher than the control group. The mechanism analysis showed that mZVI promoted electron transport system (ETS) activity (based on INTF/TS), which increased to 21.50 mg·(g·h)-1 with 10 g·L-1 mZVI compared to 13.43 mg·(g·h)-1 in the control group. Furthermore, mZVI enhanced direct interspecies electron transfer (DIET) between specific bacteria and methanogens. Microbial community analysis demonstrated that the abundance of DIET-related microorganisms, such as Syntrophomonas, Methanosarcina, and Methanobacterium, was higher in presence of mZVI.

12.
Nat Commun ; 12(1): 1798, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33741964

RESUMEN

The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 107 A/W and a specific detectivity of 2 × 1016 Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 µW/cm2.

13.
Neurosci Lett ; 751: 135830, 2021 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-33722543

RESUMEN

ErbB4 loss-of-function in catecholaminergic neurons induces catecholamine dyshomeostasis. Despite ErbB4's significant role in neuropathology, the signaling pathways that regulate these changes are still widely unknown. In this study, we attempt to identify the downstream pathway of ErbB4 that regulates catecholamine homeostasis. The SH-SY5Y human neuroblastoma cell line was used as the in vitro model for catecholaminergic neurons. Western blotting, enzyme-linked immunosorbent assay, and pharmacological and genetic manipulations by agonist/antagonist or small interference RNA were used to investigate the relationship between ErbB4 and extracellular catecholamines. We confirmed that ErbB4 is abundantly expressed in undifferentiated and retinoic acid-differentiated catecholaminergic cells from the SH-SY5Y cell line. ErbB4 inhibition increase the ratio of phosphorylated p38 to total p38 in SH-SY5Y human neuroblastoma cells. Consistent with previous in vivo observations in mice, ErbB4 deficiency led to increases in extracellular dopamine and norepinephrine levels. However, the resulting increase in extracellular dopamine, but not norepinephrine, could be suppressed by p38 inhibitor SB202190. Our results suggest that both extracellular dopamine and norepinephrine homeostasis could be regulated by ErbB4 in human catecholaminergic cells, and ErbB4 may regulate extracellular dopamine, but not norepinephrine, through the p38 MAPK signaling pathway, thus indicating different regulatory pathways of dopamine and norepinephrine by ErbB4 in catecholaminergic neurons.


Asunto(s)
Dopamina/metabolismo , Sistema de Señalización de MAP Quinasas , Receptor ErbB-4/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Línea Celular Tumoral , Células Cultivadas , Espacio Extracelular/metabolismo , Humanos , Ratones , Neuronas/metabolismo , Norepinefrina/metabolismo , Receptor ErbB-4/genética
14.
Mol Ther Nucleic Acids ; 23: 565-576, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33510944

RESUMEN

The pathogenesis of glucocorticoid (GC)-induced osteonecrosis of the femoral head (GIONFH) is still disputed, and abnormal bone metabolism caused by GCs may be an important factor. In vitro, Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cellular proliferation, and western blotting was used to investigate osteogenesis. In vivo, we used micro-computed tomography (micro-CT), H&E staining, Masson staining, and immunohistochemistry (IHC) analysis to evaluate the impact of exosomes. In addition, the mechanism by which exosomes regulate osteogenesis through the miR-365a-5p/Hippo signaling pathway was investigated using RNA sequencing (RNA-seq), luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting. The results of western blotting verified that the relevant genes in osteogenesis, including BMP2, Sp7, and Runx2, were upregulated. RNA-seq and qPCR of the exosome and Dex-treated exosome groups showed that miR-365a-5p was upregulated in the exosome group. Furthermore, we verified that miR-365a-5p promoted osteogenesis by targeting SAV1. Additional in vivo experiments revealed that exosomes prevented GIONFH in a rat model, as shown by micro-CT scanning and histological and IHC analysis. We concluded that exosomal miR-365a-5p was effective in promoting osteogenesis and preventing the development of GIONFH via activation of the Hippo signaling pathway in rats.

15.
J Sci Food Agric ; 101(6): 2472-2482, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33034040

RESUMEN

BACKGROUND: Exoinulinase catalyzes the successive removal of individual fructose moiety from the non-reducing end of the inulin molecule, which is useful for biotechnological applications like producing fructan-based non-grain biomass energy and high-fructose syrup. In this study, an exoinulinase (KmINU) from Kluyveromyces marxianus DSM 5418 was tailored for increased catalytic activity and acidic adaptation for inulin hydrolysis processes by rational site-directed mutagenesis. RESULTS: Three mutations, S124Y, N158S and Q215V distal to the catalytic residues of KmINU were designed and heterologously expressed in Pichia pastoris GS115. Compared to the wild-type, S124Y shifted the pH-activity profile towards acidic pH values and increased the catalytic activity and catalytic efficiency by 59% and 99% to 688.4 ± 17.03 s-1 and 568.93 L mmol-1 s-1 , respectively. N158S improved the catalytic activity under acidic pH conditions, giving a maximum value of 464.06 ± 14.06 s-1 on inulin at pH 4.5. Q215V markedly improved the substrate preference for inulin over sucrose by 5.56-fold, and showed catalytic efficiencies of 208.82 and 6.88 L mmol-1 s-1 towards inulin and sucrose, respectively. Molecular modeling and computational docking indicated that structural reorientation may underlie the increased catalytic activity, acidic adaptation and substrate preference. CONCLUSIONS: The KmINU mutants may serve as industrially promising candidates for inulin hydrolysis. Protein engineering of exoinulinase here provides a successful example of the extent to which mutating non-conserved substrate recognition and binding residues distal to the active site can be used for industrial enzyme improvements. © 2020 Society of Chemical Industry.


Asunto(s)
Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Glicósido Hidrolasas/química , Glicósido Hidrolasas/genética , Kluyveromyces/enzimología , Ácidos/metabolismo , Catálisis , Estabilidad de Enzimas , Proteínas Fúngicas/metabolismo , Glicósido Hidrolasas/metabolismo , Concentración de Iones de Hidrógeno , Inulina/metabolismo , Cinética , Kluyveromyces/química , Kluyveromyces/genética , Mutagénesis Sitio-Dirigida , Ingeniería de Proteínas
16.
Clin Nutr ; 40(2): 571-580, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32593523

RESUMEN

BACKGROUND: Sarcopenia is an age-dependent skeletal muscle disorder that is common in patients with heart failure. The current study aimed to investigate the associations of sarcopenia with carotid atherosclerosis, cardiovascular disease and cardiac arrhythmia in a middle-aged and elderly population without clinical heart failure. METHODS: A total of 2432 participants (992 men and 1440 women) from Shanghai Changfeng Study were included for analysis. The degree of sarcopenia was measured using height-adjusted appendicular skeletal muscle mass (ASM/height2). Carotid plaques were detected by carotid artery ultrasonography, and myocardial ischemia, infarction and cardiac arrhythmia were diagnosed based on electrocardiogram, past history and clinical manifestations. RESULTS: Sarcopenia was associated with higher prevalence of carotid atherosclerosis (26.4% vs 20.4%, P = 0.027), myocardial infarction (4.0% vs 1.1%, P = 0.001), and premature ventricular contraction (4.0% vs 2.0%, P = 0.034) in the participants with normal body weight, and higher prevalence of carotid atherosclerosis (45.0% vs 31.2%, P = 0.016), myocardial infarction (10.0% vs 4.3%, P = 0.020) and atrial fibrillation (7.5% vs 1.3%, P < 0.001) in those with overweight/obese status. After adjustment for age, gender, cigarette smoking, alcohol drinking, menopausal status in women and other metabolic and inflammatory confounding factors, sarcopenia was independently associated with the risk of myocardial infarction in the whole population, and the risk of atrial fibrillation in the overweight/obese participants (all P < 0.05). Compared with nonsarcopenic lean participants, the risk of myocardial infarction was gradually increased in sarcopenic lean (OR 3.08 [1.28-7.45], P = 0.012) and sarcopenic overweight/obese participants (OR 4.07 [1.31-12.62], P = 0.015). For the atrial fibrillation, the participants with either sarcopenia or overweight/obesity alone showed no higher risk. However, concomitant sarcopenia and overweight/obesity was associated with approximately 5-fold risk of atrial fibrillation (OR 5.68 [1.34-24.12], P = 0.019) after multiple adjustment. CONCLUSION: Sarcopenia is associated with myocardial infarction and atrial fibrillation in middle-aged and elderly adults without clinical heart failure.


Asunto(s)
Arritmias Cardíacas/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades de las Arterias Carótidas/epidemiología , Obesidad/complicaciones , Sobrepeso/complicaciones , Sarcopenia/complicaciones , Arritmias Cardíacas/etiología , Enfermedades Cardiovasculares/etiología , Enfermedades de las Arterias Carótidas/etiología , China/epidemiología , Estudios Transversales , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos
17.
Bioorg Chem ; 106: 104477, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33279250

RESUMEN

Eight phenalenone derivatives, including four new compounds, aceneoherqueinones A and B (1 and 2), (+)-aceatrovenetinone A (3a), and (+)-aceatrovenetinone B (3d), along with four known congeners, (-)-aceatrovenetinone A (3b), (-)-aceatrovenetinone B (3c), (-)-scleroderolide (4a), and (+)-scleroderolide (4b), were characterized from the marine mangrove-derived fungus Penicillium herquei MA-370. Among them, compounds 1 and 2 are rare phenalenone derivatives featuring cyclic ether unit between C-5 and C-2'. All of these compounds were subjected to chiral HPLC analysis, and the unstable stereoisomers 3a-3d, containing configurationally labile chirality centers, were characterized by online HPLC-ECD measurements supported with TDDFT-ECD calculations. The structures of these compounds were elucidated by detailed analysis of their NMR and mass spectroscopic data, and the absolute configuration of compound 1 was confirmed by X-ray diffraction analysis, while those of compounds 2 and 3a-3d were determined by TDDFT-ECD calculations of their ECD spectra. All of the isolated compounds were tested for the inhibitory activity against angiotensin-I-converting enzyme (ACE), and compounds 1 and 2 displayed activity with IC50 values 3.10 and 11.28 µM, respectively. The intermolecular interaction and potential binding sites of 1 and 2 with ACE were elaborated by molecular docking, showing that compound 1 bound well with ACE via hydrogen interactions with residues Ala261, Gln618, Trp621, and Asn624, while compound 2 interacted with residues Asp358 and Tyr360.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Penicillium/química , Peptidil-Dipeptidasa A/metabolismo , Fenalenos/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Estructura Molecular , Fenalenos/química , Fenalenos/aislamiento & purificación , Estereoisomerismo , Relación Estructura-Actividad
18.
World J Psychiatry ; 10(11): 272-285, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33269223

RESUMEN

BACKGROUND: Recently, there has been a range of studies about smartphone-based interventions and monitoring for reducing symptoms of bipolar disorder (BD). However, their efficacy for BD remains unclear. AIM: To compare the effect of smartphone-based interventions and monitoring with control methods in treating patients with BD. METHODS: A systematic literature search was performed on PubMed, Embase, Clinical trials, psycINFO, Web of Science, and Cochrane Library. Randomized clinical trials (RCTs) or single-group trials in which smartphone-based interventions and monitoring were compared with control methods or baseline in patients with symptoms of BD were included. Data were synthesized using a random-effects or a fixed-effects model to analyze the effects of psychological interventions and monitoring delivered via smartphone on psychiatric symptoms in patients with BD. The primary outcome measures were set for mania and depression symptoms. Subgroups were created to explore which aspects of smartphone interventions are relevant to the greater or lesser efficacy of treating symptoms. RESULTS: We identified ten articles, including seven RCTs (985 participants) and three single-group trials (169 participants). Analysis of the between-group study showed that smartphone-based interventions were effective in reducing manic [g = -0.19, 95% confidence interval (CI): -0.33 to -0.04, P = 0.01] and depressive (g = -0.28, 95%CI: -0.55 to -0.01, P < 0.05) symptoms. In within-group analysis, smartphone-based interventions significantly reduced manic (g = 0.17, 95%CI: 0.04 to 0.30, P < 0.01) and depressive (g = 0.48, 95%CI: 0.18 to 0.78) symptoms compared to the baseline. Nevertheless, smartphone-based monitoring systems significantly reduced manic (g = 0.27, 95%CI: 0.02 to 0.51, P < 0.05) but not depressive symptoms. Subgroup analysis indicated that the interventions with psychoeducation had positive effects on depressive (g = -0.62, 95%CI: -0.81 to -0.43, P < 0.01) and manic (g = -0.24, 95%CI: -0.43 to -0.06, P = 0.01) symptoms compared to the controlled conditions, while the interventions without psychoeducation did not (P > 0.05). The contacts between therapists and patients that contributed to the implementation of psychological therapy reduced depression symptoms (g = -0.47, 95%CI: -0.75 to -0.18, P = 0.01). CONCLUSION: Smartphone-based interventions and monitoring have a significant positive impact on depressive and manic symptoms of BD patients in between-group and within-group analysis.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1962-1971, 2020 Dec.
Artículo en Chino | MEDLINE | ID: mdl-33283727

RESUMEN

OBJECTIVE: To investigate the expressions of stromal cell-derived factor (CXCL12), stromal cell-derived factor receptor (CXCR4), vascular endothelial growth factor (VEGF) and microvessel density (MVD) in bone marrow microsputum of patients with multiple myeloma (MM) and their correlation with the prognosis. METHODS: The expressions of CXCL12, CXCR4, VEGF and MVD in bone marrow microtubules of 57 newly diagnosed MM patients and 26 normal bone marrow samples were detected by immunohistochemistry. The rank sum test was used to compare the differences between the two groups. The clinical data of the patients were collected to analyze the correlation between the indicators of the MM group and the prognosis. RESULTS: The expressions of CXCL12, CXCR4, VEGF and MVD in the bone marrow biopsy of the patients in MM group were significantly higher than those in the normal control group (P<0.05). The expressions levels of CXCL12, CXCR4, VEGF and MVD were in the bone marrow of the patients in MM group were correlated with the ISS stage, risk stratification and the proportion of plasma cells in the bone marrow (P<0.05). Univariate analysis showed that age, ISS stage, risk stratification, plasma cell ratio, expressions of CXCL12, CXCR4, VEGF, and MVD associated with the prognosis of patients with MM (P<0.05). Multivariate analysis found that expressions of CXCR4, VEGF, MVD, age, and plasma cell ratio were independent prognostic factors. CONCLUSION: The expressions of CXCL12, CXCR4, VEGF and MVD are increase in the bone marrow of patients with multiple myeloma, and their expressions levels are associate with the occurrence and development of multiple myeloma, and their high expression may indicate a poor prognosis.


Asunto(s)
Mieloma Múltiple , Factor A de Crecimiento Endotelial Vascular , Quimiocina CXCL12 , Humanos , Neovascularización Patológica , Pacientes , Pronóstico , Receptores CXCR4 , Factores de Crecimiento Endotelial Vascular
20.
J Nat Prod ; 83(12): 3652-3660, 2020 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-33322904

RESUMEN

Three new ophiobolin sesterterpenoids, (6R)-16,17,21,21-O-tetrahydroophiobolin G (1), (6R)-16,17-dihydroophiobolin H (2), and (5S,6S)-16,17-dihydroophiobolin H (3), and three new farnesylated phthalide derivatives farnesylemefuranones D-F (9-11), along with five known ophiobolin analogues (4-8), were isolated and identified from the culture extract of Aspergillus insuetus SD-512, a deep-sea-derived fungus obtained from cold seep sediments collected at a depth of 1331 m. Among them, compounds 9-11 are rare examples of phthalide derivatives linked with farnesyl moieties via ether bonds. Their structures were established on the basis of detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis, ECD calculations, and DP4+ probability analysis were performed to confirm the structures and establish the relative and absolute configurations of compounds 1-4. Compounds 3 and 9-11 showed broad-spectrum antibacterial activities, and differences in potencies could be assigned to structural modifications. This is the first report of secondary metabolites obtained from a deep sea cold-seep-derived fungus.


Asunto(s)
Aspergillus/química , Benzofuranos/aislamiento & purificación , Sesterterpenos/aislamiento & purificación , Benzofuranos/química , Frío , Océanos y Mares , Prenilación , Sesterterpenos/química , Análisis Espectral/métodos
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