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1.
Clin Rehabil ; 38(6): 749-769, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38425282

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of transcranial direct current stimulation in poststroke patients with upper extremity motor dysfunction using a systematic review and meta-analysis. DATA SOURCES: We searched the Web of Science, Cochrane Library, EMBASE, and PubMed for randomized controlled trials investigating the effects of both active and sham stimulation up until January 27, 2024. REVIEW METHODS: Efficacy, including the upper extremity Fugl-Meyer Assessment, Action Research Arm Test, Barthel Index, and safety, were assessed. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool and the Physiotherapy Evidence Database Scale. Meta-analysis was performed using the RevMan 5.4 software. RESULTS: Forty-four studies with 1555 participants were included. Transcranial direct current stimulation proved effective in improving upper extremity motor function (standardized mean difference = 0.22, 95% confidence interval: 0.12-0.32, P < 0.001) and Barthel Index (mean difference = 4.65, 95% confidence interval: 2.82-6.49, P < 0.001). Subgroup analysis revealed the highest transcranial direct current stimulation efficacy in patients with subacute stroke. Both anodal and cathodal stimulation were effective against upper extremity motor dysfunction. C3/C4 was the most effective stimulus target. Optimal stimulation parameters included stimulus current densities <0.057 mA/cm2 for 20-30 min and <30 sessions. Adverse effects and dropouts during follow-up showed that transcranial direct current stimulation is safe and feasible. CONCLUSIONS: Our findings suggest that both anodal and cathodal stimulation were significantly effective in subacute stroke patients, particularly when preceding other treatments and when C3/C4 is targeted.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación Transcraneal de Corriente Directa , Extremidad Superior , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Extremidad Superior/fisiopatología , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Recuperación de la Función , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
J Integr Plant Biol ; 66(7): 1517-1531, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38818961

RESUMEN

Parthenogenesis, the development of unfertilized egg cells into embryos, is a key component of apomixis. AtBBM (BABY BOOM), a crucial regulator of embryogenesis in Arabidopsis, possesses the capacity to shift nutritional growth toward reproductive growth. However, the mechanisms underlying AtBBM-induced parthenogenesis remain largely unexplored in dicot plants. Our findings revealed that in order to uphold the order of sexual reproduction, the embryo-specific promoter activity of AtBBM as well as repressors that inhibit its expression in egg cells combine to limiting its ability to induce parthenogenesis. Notably, AtRKD5, a RWP-RK domain-containing (RKD) transcription factor, binds to the 3' end of AtBBM and is identified as one of the inhibitory factors for AtBBM expression in the egg cell. In the atrkd5 mutant, we successfully achieved enhanced ectopic expression of AtBBM in egg cells, resulting in the generation of haploid offspring via parthenogenesis at a rate of 0.28%. Furthermore, by introducing chimeric Arabidopsis and rice BBM genes into the egg cell, we achieved a significant 4.6-fold enhancement in haploid induction through the atdmp8/9 mutant. These findings lay a strong foundation for further exploration of the BBM-mediated parthenogenesis mechanism and the improvement of haploid breeding efficiency mediated by the dmp8/9 mutant.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Partenogénesis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regiones Promotoras Genéticas/genética , Mutación/genética
3.
Neurogenetics ; 24(3): 201-208, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37289317

RESUMEN

Unlike the 1p36 microdeletion syndrome, which has been extensively described, 1p36.3 microduplications have rarely been reported. We report the two siblings of familial 1p36.3 microduplication, presenting with a severe global developmental delay, epilepsy, and a few dysmorphic features. They were referred to moderate-to-severe developmental delay (DD) and intellectual disability (ID). Both were considered eyelid myoclonus with absence of epilepsy (Jeavons syndrome). The EEG is characterized by widespread 2.5-3.5 Hz spikes and spike slow complex wave, eye closure sensitivity, and photosensitivity. The children has same dysmorphic features, including mild bitemporal narrowing and sloping forehead, sparse eyebrows, hypertelorism, ptosis, strabismus, infraorbital creases, wide nasal bridge with bulbous nasal tip, dystaxia, hallux valgus, and flat feet. Family exome sequencing revealed a maternally inherited 3.2-Mb microduplication of chromosomal band 1p36.3p36.2. However, DNA purified from blood samples of either parent did not find evidence for a microduplication of 1p36 in somatic tissue, indicating that such a mutation might be carried in the germline of the parents as gonadal mosaicism. No other family members of the affected siblings' parents were reported to be affected by the symptoms found.


Asunto(s)
Epilepsia , Discapacidad Intelectual , Niño , Humanos , Discapacidad Intelectual/genética , Mutación , Epilepsia/genética , Discapacidades del Desarrollo/genética
4.
BMC Plant Biol ; 21(1): 210, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33971813

RESUMEN

BACKGROUND: Kinesin (KIN) as a motor protein is a versatile nano-machine and involved in diverse essential processes in plant growth and development. However, the kinesin gene family has not been identified in watermelon, a valued and nutritious fruit, and yet their functions have not been characterized. Especially, their involvement in early fruit development, which directly determines the size, shape, yield and quality of the watermelon fruit, remains unclear. RESULTS: In this study, we performed a whole-genome investigation and comprehensive analysis of kinesin genes in C. lanatus. In total, 48 kinesins were identified and categorized into 10 kinesin subfamilies groups based on phylogenetic analysis. Their uneven distribution on 11 chromosomes was revealed by distribution analysis. Conserved motif analysis showed that the ATP-binding motif of kinesins was conserved within all subfamilies, but not the microtubule-binding motif. 10 segmental duplication pairs genes were detected by the syntenic and phylogenetic approaches, which showed the expansion of the kinesin gene family in C. lanatus genome during evolution. Moreover, 5 ClKINs genes are specifically and abundantly expressed in early fruit developmental stages according to comprehensive expression profile analysis, implying their critical regulatory roles during early fruit development. Our data also demonstrated that the majority of kinesin genes were responsive to plant hormones, revealing their potential involvement in the signaling pathways of plant hormones. CONCLUSIONS: Kinesin gene family in watermelon was comprehensively analyzed in this study, which establishes a foundation for further functional investigation of C. lanatus kinesin genes and provides novel insights into their biological functions. In addition, these results also provide useful information for understanding the relationship between plant hormone and kinesin genes in C. lanatus.


Asunto(s)
Citrullus/crecimiento & desarrollo , Citrullus/genética , Citrullus/metabolismo , Frutas/crecimiento & desarrollo , Frutas/genética , Frutas/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Productos Agrícolas/genética , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Estudio de Asociación del Genoma Completo
5.
J Integr Plant Biol ; 63(12): 2038-2042, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34862751

RESUMEN

Efficient genetic transformation has the potential to advance research and breeding in watermelon (Citrullus lanatus), but regeneration from tissue culture remains challenging. Previous work showed that expressing a fusion of two interacting transcription factors, GROWTH-REGULATING FACTOR4 (GRF4) and GRF-INTERACTING FACTOR1 (GIF1), improved regeneration in wheat (Triticum aestivum). By overexpressing a chimeric fusion of ClGRF4 and ClGIF1, we achieved highly efficient transformation in watermelon. Mutating the mi396 microRNA target site in ClGRF further boosted the transformation efficiency up to 67.27% in a genotype-independent manner. ClGRF4-GIF1 can also be combined with clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing tools to achieve highly efficient gene editing in watermelon, which we used to successfully create diploid seedless watermelon. This research thus puts forward a powerful transformation tool for future watermelon research and breeding.


Asunto(s)
Citrullus , Edición Génica , Sistemas CRISPR-Cas/genética , Citrullus/genética , Genotipo , Fitomejoramiento , Triticum/genética
8.
BMC Complement Altern Med ; 19(1): 370, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31842860

RESUMEN

BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.


Asunto(s)
Analgésicos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Adulto , Analgésicos/efectos adversos , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
9.
Mar Drugs ; 16(11)2018 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-30360544

RESUMEN

The chemical investigation of the culture filtrate of endophyte Alternaria sp. W-1 associated with Laminaria japonica provided a new tricycloalternarene compound, 2H-(2E)-tricycloalternarene 12a (1), together with five known analogs: (2E)-tricycloalternarene 12a (2), tricycloalternarene 3a (3), tricycloalternarene F (4), 15-hydroxyl tricycloalternarene 5b (5), and ACTG-Toxin D (6). In vitro cytotoxicity against the human hepatocellular carcinoma cell line SMMC-7721 and the human gastric carcinoma cell line SGC-7901 was evaluated by the MTT method. Compounds 1, 3, and 4 inhibited the growth of SMMC-7721 cells with IC50 values of 49.7 ± 1.1, 45.8 ± 4.6, and 80.3 ± 3.8 µg/mL, respectively, while the IC50 value of the positive control cisplatin was 6.5 ± 0.5 µg/mL. Compounds 3 and 6 also showed moderate anti-proliferation activity against SGC-7901 cells with IC50 values of 53.2 ± 2.9 and 35.1 ± 0.8 µg/mL, respectively, while the IC50 value of cisplatin was 4.5 ± 0.6 µg/mL. Further studies revealed that the in vitro anticancer activity of compound 3 to SMMC-7721 cells was related to G1 phase cell cycle arrest and cell apoptosis, and the induced apoptosis was involved in both the mitochondrial pathway and the death receptor pathway. This is the first report on the anticancer mechanism of tricycloalternarene compounds.


Asunto(s)
Alternaria/química , Antineoplásicos/farmacología , Laminaria/microbiología , Terpenos/farmacología , Alternaria/aislamiento & purificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Endófitos/química , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Terpenos/química , Proteína X Asociada a bcl-2/metabolismo
10.
Proc Natl Acad Sci U S A ; 112(40): 12432-7, 2015 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-26396256

RESUMEN

The suspensor is a temporary supporting structure of proembryos. It has been proposed that suspensor cells also possess embryogenic potential, which is suppressed by the embryo as an effect of the embryo-suspensor interaction. However, data to support this hypothesis are not yet available. In this report, using an in vivo living cell laser ablation technique, we show that Arabidopsis suspensor cells can develop into embryos after removing the embryo proper. The embryo proper plays a critical role in maintaining suspensor cell identity. However, this depends on the developmental stage; after the globular embryo stage, the suspensors no longer possess the potential to develop into embryos. We also reveal that hypophysis formation may be essential for embryo differentiation. Furthermore, we show that, after removing the embryo, auxin gradually accumulates in the top suspensor cell where cell division occurs to produce an embryo. Auxin redistribution likely reprograms the fate of the suspensor cell and triggers embryogenesis in suspensor cells. Thus, we provide direct evidence that the embryo suppresses the embryogenic potential of suspensor cells.


Asunto(s)
Arabidopsis/citología , Arabidopsis/embriología , Semillas/citología , Semillas/embriología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Diferenciación Celular , División Celular , Células Cultivadas , Glucuronidasa/genética , Glucuronidasa/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Ácidos Indolacéticos/metabolismo , Captura por Microdisección con Láser , Microscopía Confocal , Morfogénesis , Plantas Modificadas Genéticamente , Semillas/genética , Factores de Tiempo , Técnicas de Cultivo de Tejidos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
11.
Sensors (Basel) ; 18(7)2018 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-29996557

RESUMEN

Wireless Power Transfer (WPT) technology is considered as a promising approach to make Wireless Rechargeable Sensor Network (WRSN) work perpetually. In WRSN, a vehicle exists, termed a mobile charger, which can move close to sensor nodes and charge them wirelessly. Due to the mobile charger's limited traveling distance and speed, not every node that needs to be charged may be serviced in time. Thus, in such scenario, how to make a route plan for the mobile charger to determine which nodes should be charged first is a critical issue related to the network's Quality of Service (QoS). In this paper, we propose a mobile charger's scheduling algorithm to mitigate the data loss of network by considering the node's criticality in connectivity and energy. First, we introduce a novel metric named criticality index to measure node's connectivity contribution, which is computed as a summation of node's neighbor dissimilarity. Furthermore, to reflect the node's charging demand, an indicator called energy criticality is adopted to weight the criticality index, which is a normalized ratio of the node's consumed energy to its total energy. Then, we formulate an optimization problem with the objective of maximizing total weighted criticality indexes of nodes to construct a charging tour, subject to the mobile charger's traveling distance constraint. Due to the NP-hardness of the problem, a heuristic algorithm is proposed to solve it. The heuristic algorithm includes three steps, which is spanning tree growing, tour construction and tour improvement. Finally, we compare the proposed algorithm to the state-of-art scheduling algorithms. The obtained results demonstrate that the proposed algorithm is a promising one.

12.
J Exp Bot ; 68(20): 5553-5564, 2017 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-29045730

RESUMEN

We previously reported that a novel motor protein belonging to the kinesin-12 family, NtKRP, displays critical roles in regulating embryo and seed size establishment. However, it remains unknown exactly how NtKRP contributes to this developmental process. Here, we report that a 60S ribosomal protein NtRPL17 directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable embryo and seed size reduction. Structural observations of the NtRPL17-silenced embryos/seeds reveal that the embryo size reduction is due to a decrease in cell number. In these embryos, cell division cycle progression is delayed at the G2/M transition. These phenotypes are similar to that in NtKRP-silenced embryos/seeds, indicating that NtKRP and NtRPL17 function as partners in the same regulatory pathway during seed development and specifically regulate cell cycle progression to control embryo/seed size. This work reveals that NtRPL17, as a widely distributed ribosomal protein, plays a critical role in seed development and provides a new clue in the regulation of seed size. Confirmation of the interaction between NtKRP and NtRPL17 and their co-function in the control of the cell cycle also suggests that the mechanism might be conserved in both plants and animals.


Asunto(s)
Cinesinas/genética , Nicotiana/crecimiento & desarrollo , Nicotiana/genética , Proteínas de Plantas/genética , Proteínas Ribosómicas/genética , Cinesinas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Ribosómicas/metabolismo , Plantones/genética , Plantones/crecimiento & desarrollo , Semillas/genética , Semillas/crecimiento & desarrollo , Nicotiana/metabolismo
13.
BMC Surg ; 16: 9, 2016 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-26922480

RESUMEN

BACKGROUND: The aim of this study was to assess curative effect of hysteroscopic and laparoscopic myomectomy for type II submucous myomas between 3 and 5 cm in diameter and explore the optimal surgical indications. METHODS: A retrospective analysis was performed of those who underwent hysteroscopic or laparoscopic myomectomy from January 2008 to January 2013. The patients were divided into three subgroups according to the myomas diameter (namely, 30 mm ≤ myomas diameter <40 mm; 40 mm ≤ myomas diameter <50 mm; and myomas diameter ≥ 50 mm). Clinical data such as operation time, amount of bleeding, postoperative anal exsufflation time, hospital stay, and complications were collected. RESULTS: There was no significant difference regarding operation time and amount of bleeding in two groups. We found significant difference in hysteroscopic group (within-subgroup) difference regarding operation time and amount of bleeding, whereas no significant difference in the laparoscopic group, while significant differences between-subgroup differences regarding operation time. Complete removal of myoma was seen in all patients. CONCLUSIONS: Both techniques are feasible for type II submucous myomas. Laparoscopic operation has higher advantages in type II submucous myomas of greater than 4 cm in diameter whereas hysteroscopic operation has higher advantages in type II submucous myomas of lower than 4 cm in diameter.


Asunto(s)
Histeroscopía , Laparoscopía , Leiomioma/cirugía , Miomectomía Uterina/métodos , Neoplasias Uterinas/cirugía , Adulto , Femenino , Humanos , Leiomioma/patología , Tiempo de Internación , Persona de Mediana Edad , Tempo Operativo , Selección de Paciente , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Uterinas/patología , Adulto Joven
14.
Bioorg Med Chem Lett ; 25(1): 34-7, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25466190

RESUMEN

A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 µg/ml, decreased the MIC80 of fluconazole from 128.0 µg/ml to 1.0-0.5 µg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.


Asunto(s)
Amidas/química , Ácidos Cafeicos/química , Candida albicans/efectos de los fármacos , Diseño de Fármacos , Fluconazol/química , Amidas/administración & dosificación , Ácidos Cafeicos/administración & dosificación , Candida albicans/fisiología , Evaluación Preclínica de Medicamentos/métodos , Farmacorresistencia Fúngica/efectos de los fármacos , Farmacorresistencia Fúngica/fisiología , Sinergismo Farmacológico , Fluconazol/administración & dosificación , Pruebas de Sensibilidad Microbiana/métodos
15.
Plant Cell Environ ; 37(2): 499-511, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23937639

RESUMEN

Proline-rich proteins (PRPs) are known to play important roles in sexual plant reproduction. Most of the known proteins in the family were found in styles or pollen and modulate pollen tube growth. Here, we identified a novel member of the gene family, NtProRP1, which is preferentially expressed in tobacco pollen grains, pollen tubes and zygotes. NtProRP1 could be secreted into the extracellular space including the cell wall, and the predicted N-terminal signal peptide is crucial for its secretion. In NtProRP1-RNAi plants, pollen germination and pollen tube growth were significantly slower and showed zigzag or swell morphology in vitro. Early embryogenesis also exhibited aberrant development, indicative of its critical role in both pollen tube growth and early embryogenesis. Further investigation revealed that NtProRP1 plays a crucial role in osmotic stress response during pollen tube growth and is likely regulated by Tsi, a stress-responsive gene, suggesting that the regulatory mechanism is also involved in the stress response during sexual plant reproduction. These data provide evidence that NtProRP1 functions as a downstream factor of Tsi1 in the stress response and converges the stress signal into the modulation of pollen tube growth and early embryogenesis.


Asunto(s)
Nicotiana/embriología , Presión Osmótica , Proteínas de Plantas/fisiología , Tubo Polínico/crecimiento & desarrollo , Secuencia de Aminoácidos , Datos de Secuencia Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reproducción , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Alineación de Secuencia , Análisis de Secuencia de Proteína , Nicotiana/crecimiento & desarrollo , Nicotiana/fisiología
16.
Biol Pharm Bull ; 37(2): 268-73, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24492724

RESUMEN

Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C. albicans in vitro. In this study, we found that BBR inhibited both the up-regulation of CDR1 mRNA and the transport function of Cdr1p induced by fluphenazine (FNZ). Further, electrophoretic mobility shift assays suggested that the transcription activation complex of protein-DRE was disrupted by BBR, and electrospray ionization mass spectrometry analysis showed that BBR bound to the DRE of CDR1. Thus we propose that BBR inhibits the FNZ-induced transcriptional activation of CDR1 in C. albicans by blocking transcription factor binding to the DRE of CDR1. These results contribute to our understanding of the mechanism of synergistic effect of BBR and FLC.


Asunto(s)
Antifúngicos/farmacología , Berberina/farmacología , Candida albicans/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Flufenazina/efectos adversos , Proteínas Fúngicas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Extractos Vegetales/farmacología , Candida albicans/metabolismo , Sinergismo Farmacológico , Flufenazina/uso terapéutico , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Proteínas de Transporte de Membrana/genética , ARN Mensajero/metabolismo , Activación Transcripcional/efectos de los fármacos , Regulación hacia Arriba
17.
Yao Xue Xue Bao ; 49(11): 1563-8, 2014 Nov.
Artículo en Zh | MEDLINE | ID: mdl-25757282

RESUMEN

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.


Asunto(s)
Antifúngicos/farmacología , Berberina/farmacología , Candida albicans/efectos de los fármacos , Fluconazol/farmacología , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Isoquinolinas/farmacología , Pruebas de Sensibilidad Microbiana
18.
Brain Behav ; 14(8): e3638, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39099388

RESUMEN

OBJECTIVE: The right posterior parietal cortex is the core brain region of emotional processing and executive control network in the human brain, and the function of the right posterior parietal cortex is decreased in patients with major depressive disorder. This study aims to preliminarily investigate whether the excitation of the right posterior parietal cortex by transcranial direct current stimulation (tDCS) could improve their clinical symptoms. METHODS: In this study, 12 patients with major depressive disorder were given tDCS treatment at Xuanwu Hospital of Capital Medical University and the First Hospital of Hebei Medical University. The stimulating electrode (anode) was placed on the patients' right parietal cortex, whereas the reference electrode (cathode) was placed on the patients' left mastoid. The stimulation intensity was set as 2.0 mA. The patients with depressive disorder were treated for 20 min at a time twice a day for 14 consecutive days. The severity of the clinical symptoms was evaluated using the Hamilton Depression Rating Scale-17 (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS) at before and right after treatment. RESULTS: The HDRS-17 scores of patients with depressive disorder decreased significantly following the tDCS treatment compared with those before treatment (p < .001). Further analysis revealed that the patients' anxiety/somatization, cognitive deficit, retardation, and sleep disorder scores all decreased significantly after the tDCS treatment (p < .05), although there was no significant change in their weight. Moreover, the patients' HARS scores decreased significantly after the tDCS treatment when compared with those before treatment (p < .01). CONCLUSION: The right parietal cortex may be another key stimulation targets to improving the efficacy of tDCS treatment to the patients with major depressive disorder.


Asunto(s)
Trastorno Depresivo Mayor , Lóbulo Parietal , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Lóbulo Parietal/fisiopatología , Masculino , Femenino , Adulto , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/fisiopatología , Persona de Mediana Edad , Resultado del Tratamiento
19.
Stem Cells Transl Med ; 13(9): 886-897, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39159204

RESUMEN

BACKGROUND: The efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of ischemic stroke (IS) remains controversial. Therefore, this study aimed to evaluate the efficacy and safety of MSCs for IS. METHODS: A literature search until May 23, 2023, was conducted using PubMed, EMBASE, the Cochrane Library, and the Web of Science to identify studies on stem cell therapy for IS. Interventional and observational clinical studies of MSCs in patients with IS were included, and the safety and efficacy were assessed. Two reviewers extracted data and assessed the quality independently. The meta-analysis was performed using RevMan5.4. RESULTS: Fifteen randomized controlled trials (RCTs) and 15 non-randomized trials, including 1217 patients (624 and 593 in the intervention and control arms, respectively), were analyzed. MSCs significantly improved patients' activities of daily living according to the modified Rankin scale (mean difference [MD]: -0.26; 95% confidence interval [CI]: -0.50 to -0.01; P = .04) and National Institutes of Health Stroke Scale score (MD: -1.69; 95% CI: -2.66 to -0.73; P < .001) in RCTs. MSC treatment was associated with lower mortality rates in RCTs (risk ratio: 0.44; 95% CI: 0.28-0.69; P < .001). Fever and headache were among the most reported adverse effects. CONCLUSIONS: Based on our review, MSC transplantation improves neurological deficits and daily activities in patients with IS. In the future, prospective studies with large sample sizes are needed for stem cell studies in ischemic stroke. This meta-analysis has been registered at PROSPERO with CRD42022347156.


Asunto(s)
Accidente Cerebrovascular Isquémico , Trasplante de Células Madre Mesenquimatosas , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Accidente Cerebrovascular Isquémico/terapia , Células Madre Mesenquimatosas/citología , Resultado del Tratamiento
20.
Neurosci Bull ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39078594

RESUMEN

Excessive secretion of human islet amyloid polypeptide (hIAPP) is an important pathological basis of diabetic encephalopathy (DE). In this study, we aimed to investigate the potential implications of hIAPP in DE pathogenesis. Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function. We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus. In vitro assays revealed that oligodendrocytes, compared with neurons, were more prone to acidosis under exogenous hIAPP stimulation. Moreover, western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter (MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70. Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2 (YIPF2, which modulates the transfer of CD147 to the cell membrane) as a significant target. Furthermore, YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice. These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding, potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.

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