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1.
Artículo en Inglés | MEDLINE | ID: mdl-38687283

RESUMEN

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

2.
Medicina (Kaunas) ; 60(4)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38674188

RESUMEN

Background and Objectives: This study explored the efficacy of customized anti-gravity treadmill (AGT) training, with adjustments in speed and incline, on rehabilitation outcomes for stroke patients, focusing on knee extensor muscle strength, joint angle, balance ability, and activities of daily living (ADLs). Materials and Methods: In this study, 30 individuals diagnosed with a stroke were divided into three groups. Experimental group 1 (EG1) underwent training without changes to speed and incline, experimental group 2 (EG2) received training with an increased incline, and experimental group 3 (EG3) underwent training with increased speed. Initially, all participants received AGT training under uniform conditions for two weeks. Subsequently, from the third to the sixth week, each group underwent their specified training intervention. Evaluations were conducted before the intervention and six weeks post-intervention using a manual muscle strength tester for knee strength, TETRAX for balance ability, Dartfish software for analyzing knee angle, and the Korean version of the Modified Barthel Index (K-MBI) for assessing activities of daily living. Results: Within-group comparisons revealed that AGT training led to enhancements in muscle strength, balance ability, joint angle, and ADLs across all participant groups. Between-group analyses indicated that EG2, which underwent increased incline training, demonstrated significant improvements in muscle strength and balance ability over EG1. EG3 not only showed significant enhancements in muscle strength, joint angle, and ADLs when compared to EG1 but also surpassed EG2 in terms of knee strength improvement. Conclusions: In conclusion, the application of customized AGT training positively impacts the rehabilitation of stroke patients, underscoring the importance of selecting a treatment method tailored to the specific needs of each patient.


Asunto(s)
Actividades Cotidianas , Terapia por Ejercicio , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Terapia por Ejercicio/métodos , Resultado del Tratamiento , Fuerza Muscular/fisiología , Equilibrio Postural/fisiología , Sobrevivientes/estadística & datos numéricos , Accidente Cerebrovascular/fisiopatología , Prueba de Esfuerzo/métodos
3.
Medicina (Kaunas) ; 60(4)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38674266

RESUMEN

Robot-assisted gait training (RAGT) is at the cutting edge of stroke rehabilitation, offering a groundbreaking method to improve motor recovery and enhance the quality of life for stroke survivors. This review investigates the effectiveness and application of various RAGT systems, including both end-effector and exoskeleton robots, in facilitating gait enhancements. The selection process for this comprehensive analysis involved a meticulous review of the literature from databases such as PubMed, the Cochrane Library, and EMBASE, focusing on studies published between 2018 and 2023. Ultimately, 27 studies met the criteria and were included in the final analysis. The focus of these studies was on the various RAGT systems and their role in promoting gait and balance improvements. The results of these studies conclusively show that patients experience significant positive effects from RAGT, and when combined with other physiotherapy methods, the outcomes are notably superior in enhancing functional ambulation and motor skills. This review emphasizes RAGT's capability to deliver a more customized and effective rehabilitation experience, highlighting the importance of tailoring interventions to meet the specific needs of each patient.


Asunto(s)
Robótica , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/instrumentación , Robótica/métodos , Marcha/fisiología , Terapia por Ejercicio/métodos , Trastornos Neurológicos de la Marcha/rehabilitación , Trastornos Neurológicos de la Marcha/etiología , Dispositivo Exoesqueleto , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología
4.
Medicina (Kaunas) ; 60(5)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38792894

RESUMEN

This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief. Pharmacotherapy remains a cornerstone of PD management, utilizing drugs like levodopa, dopamine agonists, and others to manage symptoms and, in some cases, slow down disease progression. However, these treatments often lead to complications over time, such as motor fluctuations and dyskinesias, highlighting the need for precise dosage adjustments and sometimes combination therapies to optimize patient outcomes. Physical therapy plays a critical role in addressing the motor symptoms of PD, including bradykinesia, muscle rigidity, tremors, postural instability, and akinesia. PT techniques are tailored to improve mobility, balance, strength, and overall quality of life. Strategies such as gait and balance training, strengthening exercises, stretching, and functional training are employed to mitigate symptoms and enhance functional independence. Specialized approaches like proprioceptive neuromuscular facilitation (PNF), the Bobath concept, and the use of assistive devices are also integral to the rehabilitation process, aimed at improving patients' ability to perform daily activities and reducing the risk of falls. Innovations in technology have introduced robotic-assisted gait training (RAGT) and other assistive devices, offering new possibilities for patient care. These tools provide targeted support and feedback, allowing for more intensive and personalized rehabilitation sessions. Despite these advancements, high costs and accessibility issues remain challenges that need addressing. The inclusion of exercise and activity beyond structured PT sessions is encouraged, with evidence suggesting that regular physical activity can have neuroprotective effects, potentially slowing disease progression. Activities such as treadmill walking, cycling, and aquatic exercises not only improve physical symptoms but also contribute to emotional well-being and social interactions. In conclusion, treating PD requires a holistic approach that combines medical, surgical, and therapeutic strategies. While there is no cure, the goal is to maximize patients' functional abilities and quality of life through personalized treatment plans. This integrated approach, along with ongoing research and development of new therapies, offers hope for improving the management of PD and the lives of those affected by this challenging disease.


Asunto(s)
Enfermedad de Parkinson , Modalidades de Fisioterapia , Humanos , Enfermedad de Parkinson/terapia , Vida Independiente , Marcha/fisiología , Estimulación Encefálica Profunda/métodos , Calidad de Vida , Terapia por Ejercicio/métodos
5.
Small ; 19(12): e2206233, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36592416

RESUMEN

Albeit considerable attention to the fast-developing organic thermoelectric (OTE) materials due to their flexibility and non-toxic features, it is still challenging to design an OTE polymer with superior thermoelectric properties. In this work, two "isomorphic" donor-acceptor (D-A) conjugated polymers are studied as the semiconductor in OTE devices, revealing for the first time the internal mechanism of regioregularity on thermoelectric performances in D-A type polymers. A higher molecular structure regularity can lead to higher crystalline order and mobility, higher doping efficiency, order of energy state, and thermoelectric (TE) performance. As a result, the regioregular P2F exhibits a maximum power factor (PF) of up to 113.27 µW m-1  K-2 , more than three times that of the regiorandom PRF (35.35 µW m-1  K-2 ). However, the regular backbone also implies lower miscibility with a dopant, negatively affecting TE performance. Therefore, the trade-off between doping efficiency and miscibility plays a vital role in OTE materials, and this work sheds light on the molecular design strategy of OTE polymers with state-of-the-art performances.

6.
Medicina (Kaunas) ; 59(5)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37241089

RESUMEN

Stroke remains a leading cause of disability worldwide, with survivors often experiencing impairments in balance, pain, spasticity, and control that limit their ability to perform daily living activities. Extracorporeal shock wave therapy (ESWT) has emerged as a potential treatment modality to improve these outcomes in stroke patients. This review aims to provide a comprehensive examination of the effects of ESWT on stroke patients, focusing on the theoretical background, balance, pain reduction, muscle spasticity and control, and upper and lower extremities. This study reviewed the use of ESWT in treating balance, pain, and spasticity in stroke patients, focusing on articles published in PubMed between January 2003 and January 2023. Systematic reviews related to stroke were used to provide an overview of stroke, and a total of 33 articles related to balance, pain, and spasticity were selected. ESWT has several shock wave generation methods and application methods, and it has been shown to have positive therapeutic effects on various aspects of rehabilitation for stroke patients, such as improving balance, reducing pain, decreasing muscle spasticity and increasing control, and enhancing functional activities of the upper and lower extremities. The efficacy of ESWT may vary depending on the patient's condition, application method, and treatment area. Therefore, it is important to apply ESWT according to the individual characteristics of each patient in clinical practice to maximize its potential benefits.


Asunto(s)
Tratamiento con Ondas de Choque Extracorpóreas , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Espasticidad Muscular/etiología , Espasticidad Muscular/terapia , Tratamiento con Ondas de Choque Extracorpóreas/efectos adversos , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Actividades Cotidianas , Resultado del Tratamiento
7.
FEMS Yeast Res ; 22(1)2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36398741

RESUMEN

Saccharomyces cerevisiae is the model organism to most yeast researchers, and information obtained from its physiology is generally extrapolated to other yeasts. Studies on fatty acid transport in S. cerevisiae are based on the expression of both native fatty acid export genes as well as heterologous proteins. Starmerella bombicola, on the other hand, is an oleaginous yeast of industrial relevance but its fatty acid transport mechanisms are unknown. In this study, we attempt to use existing knowledge from S. cerevisiae to study fatty acid transport in S. bombicola, but the obtained results differ from those observed in S. cerevisiae. First, we observed that deletion of SbPRY1 in S. bombicola leads to higher fatty acid export, the opposite effect to the one previously observed for the Pry homologues in S. cerevisiae. Second, following reports that human FATP1 could export fatty acids and alcohols in S. cerevisiae, we expressed FATP1 in a fatty acid-accumulating S. bombicola strain. However, FATP1 reduced fatty acid export in S. bombicola, most likely due to its acyl-CoA synthetase activity. These results not only advance knowledge on fatty acid physiology of S. bombicola, but also improve our understanding of S. cerevisiae and its limitations as a model organism.


Asunto(s)
Saccharomyces cerevisiae , Saccharomycetales , Humanos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomycetales/genética , Saccharomycetales/metabolismo , Transporte Biológico , Ácidos Grasos/metabolismo
8.
J Nat Prod ; 85(1): 237-247, 2022 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-34935393

RESUMEN

Baicalein is a flavonoid extracted from the root of Scutellaria baicalensis (Chinese skullcap) and is consumed as part of this botanical dietary supplement to reduce oxidative stress, pain, and inflammation. We previously reported that baicalein can also modify receptor signaling through the progesterone receptor (PR) and glucocorticoid receptor (GR) in vitro, which is interesting due to the well-established roles of both PR and GR in reducing inflammation. To understand the effects of baicalein on PR and GR signaling in vivo in the uterus, ovariectomized CD-1 mice were treated with DMSO, progesterone (P4), baicalein, P4 with baicalein, and P4 with RU486, a PR antagonist, for a week. The uteri were collected for histology and RNA sequencing. Our results showed that baicalein attenuated the antiproliferative effect of P4 on luminal epithelium as well as on the PR target genes HAND2 and ZBTB16. Baicalein did not change levels of PR or GR RNA or protein in the uterus. RNA sequencing data indicated that many transcripts significantly altered by baicalein were regulated in the opposite direction by P4. Similarly, a large portion of GO/KEGG terms and GSEA gene sets were altered in the opposite direction by baicalein as compared to P4 treatment. Treatment of baicalein did not change body weight, organ weight, or blood glucose level. In summary, baicalein functioned as a PR antagonist in vivo and therefore may oppose P4 action under certain conditions such as uterine hyperplasia, fibroids, and uterine cancers.


Asunto(s)
Flavanonas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Progesterona/metabolismo , Receptores de Progesterona/genética , Útero/efectos de los fármacos , Animales , Femenino , Ratones , Ovariectomía , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Progesterona/antagonistas & inhibidores , Análisis de Secuencia de ARN/métodos , Útero/metabolismo
9.
IEEE J Solid-State Circuits ; 57(4): 1061-1074, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36186085

RESUMEN

Miniaturized and wireless near-infrared (NIR) based neural recorders with optical powering and data telemetry have been introduced as a promising approach for safe long-term monitoring with the smallest physical dimension among state-of-the-art standalone recorders. However, a main challenge for the NIR based neural recording ICs is to maintain robust operation in the presence of light-induced parasitic short circuit current from junction diodes. This is especially true when the signal currents are kept small to reduce power consumption. In this work, we present a light-tolerant and low-power neural recording IC for motor prediction that can fully function in up to 300 µW/mm2 of light exposure. It achieves best-in-class power consumption of 0.57 µW at 38° C with a 4.1 NEF pseudo-resistorless amplifier, an on-chip neural feature extractor, and individual mote level gain control. Applying the 20-channel pre-recorded neural signals of a monkey, the IC predicts finger position and velocity with correlation coefficient up to 0.870 and 0.569, respectively, with individual mote level gain control enabled. In addition, wireless measurement is demonstrated through optical power and data telemetry using a custom PV/LED GaAs chip wire bonded to the proposed IC.

10.
Int J Mol Sci ; 23(15)2022 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-35955944

RESUMEN

Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, affects and alters autophagy activity. In cell viability assays, TPEN showed cytotoxicity in HT-22 cells. TPEN treatment also increased LC3-II levels and the ratio of LC3-II to LC3-I. Western blot analysis showed that phospho-AMP-activated protein kinase levels and the ratio of phospho-AMP-activated protein kinase to total AMP-activated protein kinase increased. Protein levels of the mammalian target of rapamycin and sirtuin 1 decreased following TPEN treatment. When TPEN-treated HT-22 cells were cotreated with autophagy inhibitors, 3-methyladenine (1 mM), or bafilomycin A1 (3 nM), the TPEN-induced decrease in cell viability was exacerbated. Cotreatment with chloroquine (10 µM) partially restored cell viability. The study showed that zinc deficiency induces autophagy and may be cytoprotective in neurons. We expect our results to add a new perspective to our understanding of the neuronal pathology related to zinc deficiency.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Autofagia , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Línea Celular , Quelantes/farmacología , Etilenodiaminas/farmacología , Hipocampo/metabolismo , Mamíferos/metabolismo , Ratones , Neuronas/metabolismo , Zinc/metabolismo
11.
J Immunol ; 203(1): 127-136, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31142603

RESUMEN

Mesenchymal stem cells (MSCs) can protect against cartilage breakdown in osteoarthritis (OA) via their immunomodulatory capacities. However, the optimization strategy for using MSCs remains challenging. This study's objective was to identify the in vivo effects of metformin-stimulated adipose tissue-derived human MSCs (Ad-hMSCs) in OA. An animal model of OA was established by intra-articular injection of monosodium iodoacetate into rats. OA rats were divided into a control group and two therapy groups (treated with Ad-hMSCs or metformin-stimulated Ad-hMSCs). Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1ß, and IL-6 expression. Metformin increased the migration capacity of Ad-hMSCs with upregulation of chemokine expression. In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1ß-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3. The antinociceptive activity and chondroprotective effects were greater in OA rats treated with metformin-stimulated Ad-hMSCs than in those treated with unstimulated Ad-hMSCs. TGF-ß expression in subchondral bone of OA joints was attenuated more in OA rats treated with metformin-stimulated Ad-hMSCs. Our findings suggest that metformin offers a promising option for the clinical application of Ad-hMSCs as a cell therapy for OA.


Asunto(s)
Tejido Adiposo/citología , Antiinflamatorios/metabolismo , Condrocitos/fisiología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/fisiología , Metformina/metabolismo , Osteoartritis/terapia , Animales , Movimiento Celular , Células Cultivadas , Citoprotección , Difosfatos , Modelos Animales de Enfermedad , Humanos , Imidazoles , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Interleucina-10/metabolismo , Masculino , Nocicepción , Ratas , Ratas Wistar
12.
J Nat Prod ; 84(9): 2612-2616, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34411479

RESUMEN

The use of botanical dietary supplements for the alleviation of conditions such as hot flashes, premenstrual syndrome, and fertility is prolific worldwide. Estrogen and progesterone receptors (ER and PR) and their corresponding steroid hormones are critical for the relief of hot flashes and the treatment of patients who develop endometriosis, and these pathways can influence the development of endometrial, ovarian, and breast cancers. However, few studies have investigated or identified the natural product components in herbal supplements that act on the PR. In the current study, a new secoiridoid, demethoxy-cornuside (1), along with six known secoiridoids (2-7) were isolated from the twigs of dogwood (Cornus officinalis) by bioassay-guided isolation with a progesterone response element (PRE)/luciferase (Luc) reporter assay in Ishikawa cells. Four phytoprogestins (1, 2, 6, 7) potentiated the effect of progesterone in the PRE/Luc assay. This study demonstrates that C. officinalis components might potentiate progesterone signaling in the presence of progesterone, which could modify progesterone receptor action in hormone-responsive tissues such as the uterus and mammary gland.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cornus/química , Iridoides/farmacología , Progesterona/metabolismo , Transducción de Señal/efectos de los fármacos , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Femenino , Humanos , Iridoides/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Receptores de Progesterona
13.
Mar Drugs ; 19(8)2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34436252

RESUMEN

Ochraceopetalin (1), a mixed-biogenetic salt compound and its component 2 were isolated from the culture broths of a marine-derived fungus, Aspergillus ochraceopetaliformis. Based on combined spectroscopic and chemical analyses, the structure of 1 was determined to be a sulfonated diphenylether-aminol-amino acid ester guanidinium salt of an unprecedented structural class, while 2 was determined to be the corresponding sulfonated diphenylether. Ochraceopetaguanidine (3), the other guanidine-bearing aminol amino acid ester component, was also prepared and structurally elucidated. Compound 1 exhibited significant cytotoxicity against K562 and A549 cells.


Asunto(s)
Antineoplásicos/farmacología , Aspergillus/química , Células A549/efectos de los fármacos , Organismos Acuáticos , Humanos , Células K562/efectos de los fármacos , Relación Estructura-Actividad
14.
Small ; 16(5): e1905309, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31922652

RESUMEN

A family of the SM-axis series based on benzo[1,​2-​b:4,​5-​b']​dithiophene and 3-ethylrhodanine (RD) units with structurally different π-conjugation systems are synthesized as a means to understand the structure-property relationship of conjugated pathways in ternary non-fullerene organic solar cells (NF-OSCs) as a third component. The optical and electrochemical properties of the SM-axis are highly sensitive both to the functionalized direction and to the number of RD groups. Enhanced power conversion efficiencies (PCEs) of over 11% in ternary devices are obtained by incorporating optimal SM-X and SM-Y contents from PBDB-T:ITIC binary NF-OSCs, while a slightly lower PCE is observed with the addition of SM-XY. The results of in-depth studies using various characterization techniques demonstrate that working mechanisms of SM-axis-based ternary NF-OSCs are distinctly different from one another: an energy-transfer mechanism with an alloy-like model for SM-X, a charge transfer with the same model for SM-Y, and an energy transfer without such a structure for SM-XY. As extension of the scope, a SM-X-based ternary NF-OSC in the PM6:IT4F system also shows a greatly enhanced PCE of over 13%. The findings provide insights into the effects of conjugated pathways of organic semiconductors on mechanisms of ternary NF-OSCs, advancing the understanding for synthetic chemists, materials engineers, and device physicists.

15.
J Nat Prod ; 82(4): 937-946, 2019 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-30896942

RESUMEN

Tuberculosis is an infectious disease of global concern. Members of the diazaquinomycin (DAQ) class of natural products have shown potent and selective activity against drug-resistant Mycobacterium tuberculosis. However, poor solubility has prevented further development of this compound class. Understanding DAQ biosynthesis may provide a viable route for the generation of derivatives with improved properties. We have sequenced the genomes of two actinomycete bacteria that produce distinct DAQ derivatives. While software tools for automated biosynthetic gene cluster (BGC) prediction failed to detect DAQ BGCs, comparative genomics using MAUVE alignment led to the identification of putative BGCs in the marine Streptomyces sp. F001 and in the freshwater Micromonospora sp. B006. Deletion of the identified daq BGC in strain B006 using CRISPR-Cas9 genome editing abolished DAQ production, providing experimental evidence for BGC assignment. A complete model for DAQ biosynthesis is proposed based on the genes identified. Insufficient knowledge of natural product biosynthesis is one of the major challenges of productive genome mining approaches. The results reported here fill a gap in knowledge regarding the genetic basis for the biosynthesis of DAQ antibiotics. Moreover, identification of the daq BGC shall enable future generations of improved derivatives using biosynthetic methods.


Asunto(s)
Actinobacteria/genética , Equinomicina/análogos & derivados , Agua Dulce/microbiología , Genes Bacterianos , Familia de Multigenes , Agua de Mar/microbiología , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Equinomicina/biosíntesis , Equinomicina/química , Eliminación de Gen
16.
Mar Drugs ; 17(9)2019 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-31438635

RESUMEN

Four new peptides were isolated from the culture broths of the marine-derived fungi Aspergillus allahabadii and A. ochraceopetaliformis. Based on the results of chemical and spectroscopic analyses, two compounds (1 and 2) from A. allahabadii were determined to be cyclopentapeptides, while those from A. ochraceopetaliformis were a structurally-related cyclodepsihexapeptide (3) and its linear analog (4). In addition to the presence of a D-amino acid residue, the almost reversed sequence of peptides in 3 and 4, relative to those of the 1 and 2, is notable. These new compounds exhibited moderate inhibition against the enzyme sortase A as well as a weak inhibition against isocitrate lyase (2).


Asunto(s)
Antibacterianos/farmacología , Aspergillus/química , Bacterias/efectos de los fármacos , Péptidos Cíclicos/farmacología , Aminoaciltransferasas/antagonistas & inhibidores , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Bacterias/enzimología , Proteínas Bacterianas/antagonistas & inhibidores , Cisteína Endopeptidasas , Pruebas de Enzimas , Sedimentos Geológicos/microbiología , Isocitratoliasa/antagonistas & inhibidores , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación
17.
Cytokine ; 110: 397-403, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29921484

RESUMEN

Interleukin-5 (IL-5) is best known as key regulator in eosinophil-associated diseases such as asthma. While a connection to vascular changes in eosinophil-associated lung diseases is still elusive, recent evidence suggests that IL-5 may have an atheroprotective role. Here, we report an unexpected anti-angiogenic potential of IL-5 on vascular endothelial cells in vitro. IL-5 significantly inhibited fundamental functions of human lung microvascular endothelial cells (HMVEC-L) in vessel formation including VEGF-induced endothelial cell proliferation, migration and tube formation. Knockdown (KD) of STAT5 abolished the direct anti-angiogenic effect of IL-5 on VEGF-induced endothelial cell proliferation, migration and tube formation.


Asunto(s)
Interleucina-5/metabolismo , Neovascularización Patológica/metabolismo , Factor de Transcripción STAT5/metabolismo , Transducción de Señal/fisiología , Proteínas Supresoras de Tumor/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/metabolismo , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Humanos
18.
J Nat Prod ; 81(9): 1962-1967, 2018 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-30199256

RESUMEN

The use of botanical dietary supplements is becoming increasingly popular for the alleviation of hormonal-based conditions such as hot flashes, premenstrual syndrome, and fertility. Estrogen and progesterone receptors (ER and PR) play an essential role in these processes. However, despite the fact that many therapies used to alleviate gynecological conditions act through PR-mediated mechanisms, few studies have investigated or identified any herbal natural product components that act on this receptor. In the current study, we used a progesterone response element (PRE)-luciferase (Luc) reporter assay to identify four phytoprogestins present in a standardized red clover ( Trifolium pratense) extract. We found that the component irilone (1) potentiated the effect of progesterone in both endometrial and ovarian cancer cell lines. In these cancers, progesterone action is generally associated with positive outcomes; thus the potentiating effect of 1 may provide entirely new strategies for enhancing progesterone signaling as a means of mitigating conditions such as fibroids and endometriosis. Formononetin (3) and biochanin A (4) exhibited mixed agonist activity, while prunetin (2) acted only as an antagonist. Collectively, these results suggest that the effects of red clover extract repeatedly observed in cultured cells and the inverse correlation between risk of various cancers and flavonoid intake may be due, in part, to altered progesterone signaling.


Asunto(s)
Isoflavonas/farmacología , Extractos Vegetales/farmacología , Progesterona/farmacología , Transducción de Señal/efectos de los fármacos , Trifolium/química , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Isoflavonas/química , Isoflavonas/aislamiento & purificación , Progesterona/antagonistas & inhibidores
19.
BMC Genomics ; 18(1): 607, 2017 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-28800729

RESUMEN

BACKGROUND: Campanulaceae species are known to have highly rearranged plastid genomes lacking the acetyl-CoA carboxylase (ACC) subunit D gene (accD), and instead have a nuclear (nr)-accD. Plastid genome information has been thought to depend on studies concerning Trachelium caeruleum and genome announcements for Adenophora remotiflora, Campanula takesimana, and Hanabusaya asiatica. RNA editing information for plastid genes is currently unavailable for Campanulaceae. To understand plastid genome evolution in Campanulaceae, we have sequenced and characterized the chloroplast (cp) genome and nr-accD of Platycodon grandiflorum, a basal member of Campanulaceae. RESULTS: We sequenced the 171,818 bp cp genome containing a 79,061 bp large single-copy (LSC) region, a 42,433 bp inverted repeat (IR) and a 7840 bp small single-copy (SSC) region, which represents the cp genome with the largest IR among species of Campanulaceae. The genome contains 110 genes and 18 introns, comprising 77 protein-coding genes, four RNA genes, 29 tRNA genes, 17 group II introns, and one group I intron. RNA editing of genes was detected in 18 sites of 14 protein-coding genes. Platycodon has an IR containing a 3' rps12 operon, which occurs in the middle of the LSC region in four other species of Campanulaceae (T. caeruleum, A. remotiflora, C. takesimana, and H. asiatica), but lacks accD, clpP, infA, and rpl23, as has been found in these four species. Platycodon nr-accD contains about 3.2 kb intron between nr-accD.e1 and nr-accD.e2 at the same insertion point as in other Campanulaceae. The phylogenies of the plastid genomes and accD show that Platycodon is basal in the Campanulaceae clade, indicating that IR disruption in Campanulaceae occurred after the loss of accD, clpP, infA, and rpl23 in the cp genome, which occurred during plastid evolution in Campanulaceae. CONCLUSIONS: The plastid genome of P. grandiflorum lacks the rearrangement of the IR found in T. caeruleum, A. remotiflora, C. takesimana, and H. asiatica. The absence of accD, clpP, infA, and rpl23 in the plastid genome is a synapomorphic characteristic of Campanulaceae. The chloroplast genome phylogeny supports the hypothesis that chloroplast genomic arrangement occurred after accD nuclear transfer and loss of the four genes in the plastid of early Campanulaceae as a lineage of asterids.


Asunto(s)
Acetil-CoA Carboxilasa/genética , Núcleo Celular/genética , Transferencia de Gen Horizontal , Plastidios/genética , Platycodon/enzimología , Platycodon/genética , Secuencia de Bases , Evolución Molecular , Reordenamiento Génico , Genoma del Cloroplasto/genética , Filogenia , Platycodon/citología , Edición de ARN
20.
Nanotechnology ; 28(15): 155402, 2017 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-28303801

RESUMEN

Hybrid organic-inorganic photovoltaic devices consisting of poly(3,4-etyhlenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and n-type silicon have recently been investigated for their cost-efficiency and ease of fabrication. We demonstrate that the insertion of an ultrathin Al2O3 layer between n-Si and PEDOT:PSS significantly improves photovoltaic performance in comparison to the conventional interfacial oxide employing SiO2. A power-conversion efficiency of 11.46% was recorded at the optimal Al2O3 thickness of 2.3 nm. This result was achieved based upon increased built-in potential and improved charge collection via the electron blocking effect of Al2O3. In addition, the hydrophilicity enhanced by Al2O3 improved the coating uniformity of the PEDOT:PSS layer, resulting in a further reduction in surface recombination.

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