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1.
Bioorg Chem ; 131: 106306, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36493621

RESUMEN

Norepinephrine (NE), as an important neurotransmitter, is closely associated with the pathogenesis of anxiety and depressive disorders. Effective monitoring of NE fluctuation aids in the diagnosis of depression and the therapeutic assessment of the antidepressant intervention. The construction of novel fluorescent probes with high specificity towards NE for imaging in depression models is still in demand urgently. In this work, a novel resorufin-based red-emitting fluorescent probe for real-time tracking NE was developed. NE can significantly increase the fluorescence of probe LNE by triggering deprotection of carbonothioate ligand via nucleophilic substitution. The probe LNE demonstrated significant NE selectivity and sensitivity over other analytes in vitro. In addition, probe LNE showed a fast response time (<10 min), and the change in fluorescence signal was positively linked with NE concentration, which could be utilized to track the dysregulation of NE in vivo. More importantly, this powerful probe was successfully employed for real-time visual and imaging of NE in living cells and depression-like behavior animals.


Asunto(s)
Depresión , Norepinefrina , Ratones , Animales , Depresión/diagnóstico por imagen , Depresión/tratamiento farmacológico , Colorantes Fluorescentes , Fluorescencia , Antidepresivos/farmacología , Antidepresivos/uso terapéutico
2.
J Nurs Manag ; 30(6): 1514-1522, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34750924

RESUMEN

AIMS: To identify the associations of workplace incivility, engagement and fatigue among Chinese female nurses, and further explore whether engagement can play a mediating role. BACKGROUND: Nurses are at a high risk of fatigue. However, no research has been done to examine the associations among nurses' workplace incivility, engagement and fatigue. METHODS: The cross-sectional study was conducted in Jiangsu Province, China. Self-administered questionnaires were distributed to 1200 female nurses, including The Fatigue Scale, Workplace Incivility Scale, Gallup Workplace Questionnaire and demographic variables. Valid responses were obtained from 1035 (86.3%) of participants. Hierarchical multiple regression analysis was performed to examine the associations among workplace incivility, engagement and fatigue. RESULTS: The mean fatigue score was 6.54 ± 3.07. Workplace incivility and engagement were related to fatigue (P < .01). Engagement partly mediated the association between workplace incivility and fatigue (a*b = 0.086, bias-corrected 95% confidence interval [CI]: 0.059, 0.116; P < .01), and the proportion of the mediating effect accounted for by engagement was 33.0%. CONCLUSION: Chinese female nurses suffered from high level of fatigue. The improvement of female nurses' engagement may be helpful to alleviate the impact of workplace incivility on fatigue. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should reduce workplace incivility of female nurses by promoting engagement to reduce fatigue.


Asunto(s)
Incivilidad , Personal de Enfermería en Hospital , Estudios Transversales , Fatiga/etiología , Femenino , Humanos , Encuestas y Cuestionarios , Lugar de Trabajo
3.
Bioorg Med Chem ; 50: 116466, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34700239

RESUMEN

Based on the higher mitochondrial membrane potential (Δψm) of tumor cells than normal cells, a mitochondria-targeting strategy using delocalized lipophilic cations as carriers is a promising way to improve the antitumor effect of small molecules and to reduce toxicity. Triptolide (TP) has a strong antitumor effect but is limited in the clinic due to high systemic toxicity. Mitochondria-targeted TP derivatives were designed and synthesized using triphenylphosphine cations as carriers. The optimal derivative not only maintained the antitumor activity of TP but also showed a tumor cell selectivity trend. Moreover, the optimal derivative increased the release of lactate dehydrogenase and the production of ROS, decreased Δψm, and arrested HepG2 cells in G0/G1 phase. In a zebrafish HepG2 xenograft tumor model, the inhibitory effect of the optimal derivative was comparable to that of TP, while it had no obvious toxic effect on multiple indicators in zebrafish at the test concentrations. This work provided some evidence to support the mitochondria-targeting strategy.


Asunto(s)
Antineoplásicos/farmacología , Diterpenos/farmacología , Mitocondrias/efectos de los fármacos , Compuestos Organofosforados/farmacología , Fenantrenos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos/síntesis química , Diterpenos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Epoxi/síntesis química , Compuestos Epoxi/química , Compuestos Epoxi/farmacología , Humanos , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Compuestos Organofosforados/química , Fenantrenos/síntesis química , Fenantrenos/química , Relación Estructura-Actividad , Pez Cebra/embriología
4.
Proc Natl Acad Sci U S A ; 113(37): E5501-10, 2016 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-27573822

RESUMEN

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.


Asunto(s)
Giro Dentado/metabolismo , Dopamina/metabolismo , Hipocampo/metabolismo , Memoria/fisiología , Animales , Conducta de Elección/fisiología , Giro Dentado/fisiología , Neuronas Dopaminérgicas/metabolismo , Hipocampo/fisiología , Aprendizaje/fisiología , Memoria Episódica , Recuerdo Mental/fisiología , Ratones , Ratones Transgénicos , Plasticidad Neuronal/genética , Plasticidad Neuronal/fisiología , Recompensa
5.
Mitochondrial DNA B Resour ; 9(10): 1418-1423, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39439864

RESUMEN

Rhabdophis chiwen is currently found so far in Sichuan Province, China, where it predominantly feeds on earthworms and firefly larvae. In this study, we sequenced and analyzed the mitochondrial genome of R. chiwen, which measured 17,646 bp in length and encompassed 37 genes along with two control regions. The base composition revealed percentages of 33.20% A, 25.94% T, 13.27% G, and 27.59% C. Phylogenetic analyses indicate that R. chiwen belongs to the family Colubridae and forms a sister branch with R. tigrinus. This study successfully obtained the first complete mitochondrial genome of R. chiwen, offering crucial genetic data for its evolutionary history and conservation.

6.
Sci Data ; 11(1): 850, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117633

RESUMEN

Rhabdophis nuchalis, a snake widely distributed in China, possesses a unique trait: glands beneath the skin on its neck and back, known as nucho-dorsal glands. These features make it a valuable subject for studying genetic diversity and the evolution of complex traits. In this study, we obtained a high-quality chromosome-level reference genome of R. nuchalis using MGI short-read sequencing, PacBio Revio long-read sequencing, and Hi-C sequencing techniques. The final assembly comprised 1.92 Gb of the R. nuchalis genome, anchored to 20 chromosomes (including 9 macrochromosomes and 11 microchromosomes), with a contig N50 of 104.79 Mb, a scaffold N50 of 204.96 Mb, and a BUSCO completeness of 97.50%. Additionally, we annotated a total of 1.09 Gb of repetitive sequences (which constitute 56.51% of the entire genome) and identified 22,057 protein-coding genes. This high-quality reference genome of R. nuchalis furnishes essential genomic data for comprehending the genetic diversity and evolutionary history of the species, as well as for facilitating species conservation efforts and comparative genomics studies.


Asunto(s)
Cromosomas , Genoma , Animales , Anotación de Secuencia Molecular , Serpientes/genética
7.
Neurosci Bull ; 39(4): 617-630, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36342657

RESUMEN

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.


Asunto(s)
Prosencéfalo Basal , Trastorno Depresivo Mayor , Ratas , Ratones , Animales , Ratas Sprague-Dawley , Trastorno Depresivo Mayor/metabolismo , Depresión , Hipocampo/metabolismo , Colinérgicos
8.
J Ethnopharmacol ; 277: 114206, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34000366

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Genus Sapium, belonging to Euphorbiaceae family, has a wide distribution in Asia and in temperate and tropical regions of Africa and America. The various parts of Sapium species have been used in traditional Chinese herbal medicine for the treatment of edema, skin-related diseases, bacterial infections, cancers, diabetes, and other ailments. AIM OF THE STUDY: A comprehensive and updated review on the phytochemistry, pharmacology, and traditional medicinal uses of Sapium has been summarized and discussed to facilitate further exploitation of the therapeutic values of Sapium species. MATERIALS AND METHODS: The relevant information of Sapium species was collected by scientific search engines including Elsevier, Google Scholar, Scifinder, and CNKI (China national knowledge infrastructure), and Master's dissertations and Summon from Shandong University Library. RESULTS: Phytochemical studies revealed that approximately 259 compounds including terpenoids, phenylpropanoids, flavonoids, tannins, steroids, alkaloids, etc. have been isolated and identified from Sapium species, among which terpenoids, phenylpropanoids and tannins are the main constituents. Pharmacological in vitro and in vivo studies revealed that the extracts and pure compounds possessed significant antibacterial, antiinflammatory, antioxidant, antihypertensive effects, cytotoxicity, antidiabetic, molluscicidal effects. Terpenoids, phenylpropanoids, tannins, flavonoids, and alkaloids may be responsible for these activities. CONCLUSIONS: The traditional uses, phytochemistry, and pharmacology described in this article demonstrated that the plants of Sapium genus possess many different types of compounds exhibiting wide range of biological activities, and they have high medicinal value and potential in the treatment of a variety of diseases. Detailed phytochemical studies have been conducted on only twelve species in the literature. More wide-ranging studies are still needed to explore this genus. Most of the existing bioactivity-related studies were implemented on crude extracts. More in-depth studies are necessary to reveal the links between the traditional uses and bioactivity in the future.


Asunto(s)
Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Sapium/química , Animales , Etnofarmacología , Humanos , Medicina Tradicional China/métodos , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química
9.
J Med Chem ; 63(20): 11786-11800, 2020 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-32996316

RESUMEN

Mitochondrion is a favorable therapeutic target in cancer, given its regulation of bioenergetics and cell death. Honokiol exhibits antiproliferative effects through mitochondria-mediated death signaling. To enhance its anticancer potential and selectivity, we conjugated honokiol to berberine, a mitochondria-targeting carrier. All designed derivatives displayed 1 order of magnitude increased cytotoxicity compared with the parent compounds, especially with massive cytoplasmic vacuoles. Biological evaluation demonstrated the representative compound 6b localized within the mitochondria, and mitochondrial dilation resulted in vacuolization. 6b induced vacuolation-associated cell death and apoptosis with obvious mitochondrial dysfunction, as demonstrated by booming reactive oxygen species generation, opening mitochondrial permeability transition pore, and reducing mitochondrial membrane potential. The targeting property also conferred 6b with selectivity for tumor cells compared to normal cells. 6b inhibited cancer cell proliferation in the zebrafish xenograft model. These results demonstrate that berberine-linked honokiol derivatives open up a direction for novel mitochondrial-targeting antitumor agents.


Asunto(s)
Antineoplásicos/farmacología , Berberina/farmacología , Compuestos de Bifenilo/farmacología , Lignanos/farmacología , Mitocondrias/efectos de los fármacos , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Berberina/química , Compuestos de Bifenilo/síntesis química , Compuestos de Bifenilo/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Lignanos/síntesis química , Lignanos/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad
10.
Cell Rep ; 26(8): 2052-2063.e4, 2019 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-30784588

RESUMEN

Retroactive interference (RI) occurs when new incoming information impairs an existing memory, which is one of the primary sources of forgetting. Although long-term potentiation (LTP) reversal shows promise as the underlying neural correlate, the key molecules that control the sensitivity of memory circuits to RI are unknown, and the developmental trajectory of RI effects is unclear. Here we found that depotentiation in the hippocampal dentate gyrus (DG) depends on GluN2A-containing NMDA receptors (NMDARs). The susceptibility of LTP to disruption progressively increases with the rise in the GluN2A/GluN2B ratio during development. The vulnerability of hippocampus-dependent memory to interference from post-learning novelty exploration is subject to similar developmental regulation by NMDARs. Both GluN2A overexpression and GluN2B downregulation in the DG promote RI-induced forgetting. Altogether, our results suggest that a switch in GluN2 subunit predominance may confer age-related differences to depotentiation and underlie the developmental decline in memory resistance to RI.


Asunto(s)
Giro Dentado/metabolismo , Memoria , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Giro Dentado/crecimiento & desarrollo , Giro Dentado/fisiología , Femenino , Potenciación a Largo Plazo , Masculino , Ratones , Ratones Endogámicos C57BL , Neurogénesis , Multimerización de Proteína
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