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1.
Opt Express ; 31(5): 7351-7362, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36859868

RESUMEN

Nascent data-intensive emerging technologies are mandating low-loss, short-range interconnects, whereas existing interconnects suffer from high losses and low aggregate data throughput owing to a lack of efficient interfaces. Here, we report an efficient 22-Gbit/s terahertz fiber link using a tapered silicon interface that serves as a coupler between the dielectric waveguide and hollow core fiber. We investigated the fundamental optical properties of hollow-core fibers by considering fibers with 0.7-mm and 1-mm core diameters. We achieved a coupling efficiency of ∼ 60% with a 3-dB bandwidth of 150 GHz in the 0.3-THz band over a 10 cm fiber.

2.
Molecules ; 27(2)2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35056740

RESUMEN

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the "double-locked" strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-ß-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of ß-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first "key") and pH (second "key"), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Medicina de Precisión/métodos , Animales , Antineoplásicos/química , Línea Celular Tumoral , Femenino , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Ratones Endogámicos BALB C , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/cirugía , Neoplasias Experimentales/terapia , Nitrorreductasas/metabolismo , Ratas , Espectrometría de Fluorescencia , Cirugía Asistida por Computador , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Opt Lett ; 46(21): 5469-5472, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34724503

RESUMEN

All-silicon effective-medium-clad waveguides are a promising candidate for an integrated terahertz platform with high efficiency and broad bandwidth. Waveguide crossings are essential circuit components, allowing for wave routing over shorter paths to increase circuit density. However, the simple intersection of two orthogonal effective-medium-clad waveguides results in terahertz wave scattering, leading to relatively high cross talk. In this work, a low-loss, 40% fractional bandwidth crossing utilizing Maxwell-Garnet effective-medium theory and wavefront planarization techniques is proposed. This monolithic structure is fabricated on a single high-resistivity float-zone silicon wafer using a deep reactive ion etching process with a modest 4.4 mm diameter (4.03λ0) structure footprint. Experimentally verified results show low insertion loss, less than 1 dB, and average cross talk level of -39dB for both E11x and E11y operating modes, over 220-330 GHz with a 40% fractional bandwidth. This waveguide crossing can be foreseen as a useful routing component for terahertz all-silicon integrated circuits. The proposed techniques are applicable to other dielectric waveguide platforms at infrared and optical frequencies.

4.
Opt Express ; 27(26): 38721-38734, 2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31878634

RESUMEN

Terahertz integrated platforms with high efficiency are crucial in a broad range of applications including terahertz communications, radar, imaging and sensing. One key enabling technology is wideband interconnection. This work proposes substrate-less all-dielectric waveguides defined by an effective medium with a subwavelength hole array. These self-supporting structures are built solely into a single silicon wafer to minimize significant absorption in metals and dielectrics at terahertz frequencies. In a stark contrast to photonic crystal waveguides, the guiding mechanism is not based on a photonic bandgap but total internal reflections The waveguides are discussed in the context of terahertz communications that imposes stringent demands on performance. Experimental results show that the realized waveguides can cover the entire 260-400 GHz with single dominant modes in both orthogonal polarizations and an average measured attenuation around 0.05 dB/cm. Limited by the measurement setup, the maximum error-free data rate up to 30 Gbit/s is experimentally achieved at 335 GHz on a 3-cm waveguide. We further demonstrate the transmission of uncompressed 4K-resolution video across this waveguide. This waveguide platform promises integration of diverse active and passive components. Thus, we can foresee it as a potential candidate for the future terahertz integrated circuits, in analogy to photonic integrated circuits at optical frequencies. The proposed concept can potentially benefit integrated optics at large.

5.
J Nat Prod ; 82(6): 1442-1450, 2019 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-31120744

RESUMEN

Naturally occurring ß-carbolines are known to have antitumor activities but with limited effectiveness. In order to improve their efficacy, a series of new hydroxamic-acid-containing ß-carbolines connected via a hydroxycinnamic acid moitey (12a-f) were developed to incorporate histone deacetylase (HDAC) inhibition for possible synergistic effects. When evaluated in in vitro assays, most of the analogues showed significant antitumor activities against four human cancer cells. In particular, 12b showed the highest cytotoxic potency of the series, including drug-resistant Bel7402 cells, but had minimal effect on normal hepatic LO2 cells. These compounds also showed excellent inhibitory effects against HDAC1/6, which appear to contribute greatly to their antiproliferative properties. Compound 12b enhanced the acetylation levels of histone H3 and α-tubulin and induced greater cancer cell apoptosis than the FDA-approved HDAC inhibitor SAHA by regulating expression of apoptotic proteins Bax, Bcl-2, and caspase 3. Importantly, 12b also induced a significant amount of autophagic flux activity in Bel7402 cells by increasing the expression of Beclin-1 and LC3-II proteins and decreasing that of LC3-I and p62. Finally, 12b significantly inhibited PI3K/Akt/mTOR signaling, an important cell-growth-promoting pathway aberrantly activated in many cancers. Together, the results suggest that these hydroxamic-acid-containing ß-carboline derivatives may be new leads for the discovery of agents for the treatment of human carcinoma cancers.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Beclina-1/química , Carbolinas/farmacología , Caspasa 3/farmacología , Proliferación Celular/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/química , Serina-Treonina Quinasas TOR/metabolismo , Acetilación , Antineoplásicos/química , Carbolinas/química , Caspasa 3/química , Línea Celular Tumoral , Ácidos Cumáricos , Histona Desacetilasa 1/química , Histona Desacetilasa 1/metabolismo , Inhibidores de Histona Desacetilasas/química , Humanos , Ácidos Hidroxámicos/química , Estructura Molecular , Fosfatidilinositol 3-Quinasas/química , Proteínas Proto-Oncogénicas c-akt/química , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/química , Proteína X Asociada a bcl-2/química , Proteína X Asociada a bcl-2/metabolismo
6.
Med Sci Monit ; 25: 771-777, 2019 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-30685767

RESUMEN

BACKGROUND Tripartite motif containing 55 (TRIM55) plays a regulatory role in assembly of sarcomeres, but few studies have assessed its function in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Immunohistochemistry (IHC) was used to detect expression of TRIM55 in tissues samples of HCC patients. Transwell assay was used to study migration and invasion ability of HCC cells. Western blot and immunofluorescence (IF) were used to analyze mechanism of TRIM55 in cell migration and invasion. RESULTS We found TRIM55 was downregulated in HCC tissues and was associated with prognosis of HCC patients. Cox regression analysis showed that TRIM55 was an independent risk factor of prognosis of HCC patients. Overexpression of TRIM55 was associated with lower cell migration and invasion ability, and it led to high expression of E-cadherin and low expression of Vimentin and MMP2. CONCLUSIONS Our study found TRIM55 is an independent factor affecting the prognosis of HCC patients, and overexpression of TRIM55 inhibits migration and invasion of HCC cells through epithelial-mesenchymal transition and MMP2.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Proteínas de Motivos Tripartitos/biosíntesis , Ubiquitina-Proteína Ligasas/biosíntesis , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Regulación hacia Abajo , Transición Epitelial-Mesenquimal , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Modelos de Riesgos Proporcionales , Transducción de Señal , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
7.
Chemistry ; 24(71): 19053-19059, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30222213

RESUMEN

Two 9,10-distyrylanthracene-based luminophores exhibiting aggregation-induced emission and stimuli-responsive properties were synthesized. Seven- or five-color luminescence switching based on a single organic molecule was achieved for the first time. These phase transitions can be induced by physical stimuli such as grinding by mortar and pestle, heating, and exposure to the vapors of organic solvents. Moreover, a strategy for the design of new mechanoresponsive materials with π-conjugated luminophores is proposed.

8.
J Clin Nurs ; 27(5-6): e1013-e1021, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29076204

RESUMEN

AIMS AND OBJECTIVES: To reveal nurses' self-reported practice of managing chest tubes and to define decision-makers for these practices. BACKGROUND: No consensus exists regarding ideal chest-tube management strategy, and there are wide variations of practice based on local policies and individual preferences, rather than standardised evidence-based protocols. DESIGN: This article describes a cross-sectional study. METHODS: Questionnaires were emailed to 31 hospitals in Tianjin, and the sample consisted of 296 clinical nurses whose work included nursing management of chest drains. The questionnaire, which was prepared by the authors of this research, consisted of three sections, including a total of 22 questions that asked for demographic information, answers regarding nursing management that reflected the practice they actually performed and who the decision-makers were regarding eight chest-drain management procedures. McNemar's test was used to analyse the data. RESULTS: The results indicated that most respondents thought that it was necessary to manipulate chest tubes to remove clots impeding unobstructed drainage (91.2%). Most respondents indicated that dressings would be changed when the dressing was dysfunctional. At the same time, more than half of respondents approved of changing dressings routinely, and the frequency of changing dressings varied. When drainage was employed for pleural effusion and for a pneumothorax, 64.6% and 94.5% of respondents, respectively, considered that underwater seal-drainage bottles should be changed routinely, and the frequency of changing bottles both varied. The results indicated that nurses were the primary decision-makers in the replacement of chest tubes, manipulation of chest tubes and monitoring of drainage fluid. CONCLUSIONS: There was considerable variation in respondents' self-reported clinical nursing practice regarding management of chest drains. The rationale on which respondents' practices were based also varied greatly. This study indicated that nurses were the primary decision-makers for three of eight procedures regarding management of chest drains, which reflects that clinical nurses' decision-making power regarding management of chest drains was weak. RELEVANCE TO CLINICAL PRACTICE: This study describes the nurse-reported practices of Chinese nurses from Tianjin, including changing and selecting dressing types, manipulating chest tubes, clamping drains and replacing drainage bottles, and the study defines who the decision-makers were for these interventions. By focusing on nurses' self-report of behaviours in managing chest drains (actual nursing practice vs. nursing knowledge), this article also relates the literature to the research findings and denotes the gaps in knowledge for future research.


Asunto(s)
Tubos Torácicos/normas , Drenaje/enfermería , Pautas de la Práctica en Enfermería , Adulto , Vendajes , China , Toma de Decisiones Clínicas , Consenso , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Autoinforme
9.
Apoptosis ; 19(4): 668-81, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24337869

RESUMEN

This report is designed to study the ability of the combined treatment with gemcitabine (Gem) and dihydroartemisinin (DHA) to induce apoptosis in a non-small-cell lung cancer cell line (A549 cells). This combination treatment synergistically inhibited cell growth by inducing apoptosis, and this synergistic action was not associated with reactive oxygen species (ROS). Although either Gem or DHA induced a significant increase in ROS generation, the combination treatment did not further enhance ROS level. Compared with single drugs, the combination treatment significantly potentiated Bak activation, loss of mitochondrial membrane potential, caspase-9 and -3 activation, indicating the important role of the Bak-mediated intrinsic apoptosis pathway in the synergistic action, which was further verified by the significant prevention of the cytotoxicity of the combination treatment by inhibiting one of caspase-9, -3 and Bcl-xL or silencing Bak. In addition, the combination treatment also synergistically activated caspase-8, and inhibition of Fas and caspase-8 presented significant prevention on the cytotoxicity of the combination treatment, indicating that the Fas-caspase-8-mediated extrinsic apoptosis pathway partially participated in the synergistic action. Collectively, the present study demonstrates a strong synergistic action of the combined treatment with Gem and DHA in inducing apoptosis of A549 cells via both the Bak-mediated intrinsic pathway and the Fas-caspase-8-mediated extrinsic pathway.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Artemisininas/farmacología , Desoxicitidina/análogos & derivados , Línea Celular Tumoral , Desoxicitidina/farmacología , Sinergismo Farmacológico , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Receptor fas/metabolismo , Gemcitabina
10.
Int J Nurs Pract ; 20(1): 70-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24580977

RESUMEN

The aim of this paper was to evaluate reporting and methodological quality of systematic reviews or meta-analyses in the nursing field in China. Over the last decade, evidence-based nursing has been gradually known and accepted by nurses in China, and the number of systematic reviews or meta-analyses of nursing flied has steadily increased, but the quality of these reviews is unsatisfactory. The Chinese Journal Full-Text Database, the Chinese Biomedicine Literature Database and the Wanfang Database were searched for systematic reviews or meta-analyses in the nursing field, from inception through December 2011. The Preferred Reporting Items of Systematic Reviews and Meta-analyses and the Assessment of Multiple Systematic Reviews checklists were used to assess reporting characteristics and methodological quality, respectively. A total of 63 systematic reviews or meta-analyses were identified. The deficiencies of methodological quality were mainly in literature searches, heterogeneity handling, recognition and assessment of publication bias. In addition, the deficiencies of reporting characteristics were reflected in incomplete reporting of literature search, quality assessment, risk of bias and results. Focusing on improving the quality of reporting and methodological quality of systematic reviews or meta-analyses in the nursing field in China is urgently needed.


Asunto(s)
Proceso de Enfermería , China
11.
Sheng Wu Gong Cheng Xue Bao ; 40(3): 943-952, 2024 Mar 25.
Artículo en Zh | MEDLINE | ID: mdl-38545989

RESUMEN

The biotechnology industry is a strategic emerging industry in our country, holding a crucial position in the national economy. The training of innovative high-quality professionals carries immense significance. As the cornerstone course in biotechnology, "Enzyme Engineering" directly impacts the students' caliber and industry development. This course aims to address pertinent issues present in the current curriculum delivery, such as inadequately optimized content, excessive dependency on textbooks, and reliance on monotonous teaching methods. By adjusting the course outline, updating the case material repository, and engaging students' enthusiasm, we developed a three-dimensional approach to instruct. This approach included a blend of online and offline components, interactive teaching through the flipped classroom methodology, heuristic teaching using problem-based learning (PBL) mode, and topic teaching via case studies. We also improved the assessment mechanism to stimulate students' enthusiasm for learning nurture their innovation capabilities. Our objective was to foster high-quality professionals with a robust foundation and practical expertise. Through teaching exploration and practice, we have witnessed significant improvement in both teaching efficacy and students' engineering practice and innovation abilities.


Asunto(s)
Curriculum , Aprendizaje Basado en Problemas , Humanos , Estudiantes , Aprendizaje , Biotecnología
12.
Biol Psychiatry ; 95(5): 389-402, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37678540

RESUMEN

BACKGROUND: LHPP was recently shown to be a risk gene for major depressive disorder. LHPP has been proven to dephosphorylate the residues of histidine, serine, threonine, and tyrosine. However, much remains unknown about how LHPP contributes to depression. METHODS: In the current study, we addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing, and electrophysiology. RESULTS: We found that levels of LHPP were upregulated in glutamatergic neurons of the ventral hippocampus in mice that displayed stress-induced depression-like behaviors. Knockout of LHPP in glutamatergic neurons of the brain improved the spontaneous activity of LHPPflox/flox·CaMKIIαCre+ (conditional knockout) mice. Adeno-associated virus-mediated LHPP knockdown in the ventral hippocampus enhanced resistance against chronic social defeat stress in mice. Manipulations of LHPP levels impacted the density of dendritic spines and excitability of CA1 pyramidal neurons by mediating the expressions of BDNF (brain-derived neurotrophic factor) and PSD95 via the modulation of the dephosphorylation of CaMKIIα and ERK. Notably, compared with wild-type LHPP, human mutant LHPP (E56K, S57L) significantly increased the activity of the CaMKIIα/ERK-BDNF/PSD95 signaling pathway. Finally, esketamine, not fluoxetine, markedly alleviated the LHPP upregulation-induced depression-like behaviors. CONCLUSIONS: These findings provide evidence that LHPP contributes to the pathogenesis of depression via threonine and serine hydrolases, thereby identifying LHPP as a potential therapeutic target in treating patients with major depressive disorder.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Trastorno Depresivo Mayor , Humanos , Ratones , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/metabolismo , Ratones Noqueados , Hipocampo/metabolismo , Neuronas/metabolismo , Serina/metabolismo , Treonina/metabolismo , Estrés Psicológico/tratamiento farmacológico
13.
Cancer Lett ; 586: 216708, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38336287

RESUMEN

Intratumor heterogeneity is one of the major features of cancers, leading to aggressive disease and treatment failure. Cancer stem-like cells (CSCs) are believed to give rise to the heterogeneous cell types within tumors. Hence, understanding the regulatory mechanism underlying the recurrence process of heterogeneous tumor by CSCs could facilitate the development of CSC-targeted therapies. Here, utilizing single-cell transcriptomics, we present the molecular profile of osteosarcoma CSCs-derived heterogeneous tumors consisting of CSC clusters, osteoprogenitor and differentiated cell types, such as pre-osteoblasts, osteoblasts and chondroblasts. Furthermore, by constructing the comprehensive map of modulated genes during CSCs self-renewal and differentiation, we identify RAN exhibiting specific peak expression in osteosarcoma CSCs clusters which is transcriptionally up-regulated by MYBL2. Functionality, MYBL2-RAN pathway promotes the CSCs self-renewal by enhancing the nuclear accumulation of MYC protein, which in turn boosts the overexpression of RAN as a positive feedback. Importantly, blockage of MYBL2-RAN pathway sensitizes CSCs to cisplatin treatment and synergistically enhanced the cisplatin-induced cytotoxicity. Both MYBL2 and RAN are highly expressed in clinical osteosarcoma tissues which indicate poor prognosis. Collectively, our study provides advanced insights into the regeneration process of heterogeneous tumor originating from CSCs and highlights the MYBL2-RAN pathway as a promising target for CSC-based therapy in osteosarcoma.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Neoplasias Óseas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Células Madre Neoplásicas/metabolismo , Osteosarcoma/tratamiento farmacológico , Transactivadores/metabolismo , Regulación hacia Arriba
14.
Apoptosis ; 18(10): 1201-13, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23661289

RESUMEN

This report is designed to explore the roles of caspase-8, -9 and -3 in artemisinin (ARTE)-induced apoptosis in non-small cell lung cancer cells (A549 cells). ARTE induced reactive oxygen species (ROS)-mediated apoptosis in dose- and time-dependent fashion. Although ARTE treatment did not induce Bid cleavage and significant loss of mitochondrial membrane potential, it induced release of Smac and AIF but not cytochrome c from mitochondria, and silencing of Bak but not Bax significantly prevented ARTE-induced cytotoxicity. Moreover, ARTE treatment induced ROS-dependent activation of caspase-9, -8 and -3. Of the utmost importance, silencing or inhibiting any one of caspase-8, -9 and -3 almost completely prevented ARTE-induced activation of all the three caspases and remarkably abrogated the cytotoxicity of ARTE, suggesting that ARTE triggered an amplification activation loop among caspase-9, -8 and -3. Collectively, our data demonstrate that ARTE induces a ROS-mediated amplification activation loop among caspase-9, -8 and -3 to dominantly mediate the apoptosis of A549 cells.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Artemisininas/farmacología , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/biosíntesis , Línea Celular Tumoral , Activación Enzimática , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos
15.
Neurochem Int ; 169: 105589, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37543308

RESUMEN

As a ubiquitous RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) interacts with numerous nucleic acids and proteins and is involved in various cellular functions. Available literature indicates that it can regulate dendritic spine density through the extracellular signal-regulating kinase (ERK) - brain-derived neurotrophic factor (BDNF) pathway, which is crucial to retain the synaptic plasticity in patients with major depressive disorder (MDD) and mouse depression models. However, ERK upstream regulatory kinase has not been fully elucidated. Furthermore, it remains unexplored whether hnRNPK may impact the depressive condition via the ERK pathway. The present study addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing. We found that hnRNPK in the brain was mainly distributed in the hippocampal neurons; that it was significantly downregulated in mice that displayed stress-induced depression-like behaviors; and that the level of hnRNPK markedly decreased in MDD patients from the GEO database. Further in vivo and in vitro analyses revealed that the changes in the expressions of BDNF and PSD95 and in the phosphorylation of ERK (Thr202/Tyr204) paralleled the variation of hnRNPK levels in the ventral hippocampal neurons in mice with depression-like behaviors. Finally, esketamine treatment significantly increased the level of hnRNPK in mice. These findings evidence that hnRNPK involved in the pathogenesis of depression via the ERK-BDNF pathway, pinpointing hnRNPK as a potential therapeutic target in treating MDD patients.


Asunto(s)
Depresión , Trastorno Depresivo Mayor , Animales , Ratones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Hipocampo/metabolismo , Transducción de Señal , Sistema de Señalización de MAP Quinasas
16.
Artículo en Inglés | MEDLINE | ID: mdl-38057370

RESUMEN

Cognitive deterioration and memory decline associated with the progression of Alzheimer's disease (AD) primarily results from synaptic failure. However, current understanding of the upstream regulatory mechanisms controlling synaptic plasticity remains limited. Salt-inducible kinase 3 (SIK3) is central to the signal pathway and is involved in neuronal regulation of sleep duration in mice. We speculated that the SIK3 cascade signaling pathway might contribute to the pathogenesis of AD. Thus, the present study employed AD transgenic mouse models, Morris Water Maze, virus-mediated gene transfer, electrophysiology, co-immunoprecipitation, western blotting, quantitative polymerase chain reaction, immunofluorescence, ChIP-qPCR, Golgi-Cox staining and dendritic spine analysis to investigate this connection. Our results revealed that SIK3 mRNA/protein expression was significantly reduced in middle-aged AD transgenic mouse models and AD patients. Conditional deletion of SIK3 gene in dorsal hippocampal neurons of 5×FAD mice further accelerated cognitive deterioration and impaired synaptic plasticity. In hippocampal neuronal cultures, SIK3 formed a complex with HDAC4, directly phosphorylated HDAC4 and regulated its nuclear cytoplasmic shuttle. Overexpression of SIK3 could facilitate the expression of synaptic plasticity-related genes by directly repressing mef2c or involving the recruitment of histone deacetylase to promoter regions of target genes through regulation of p-HDAC4, and vice versa. Moreover, up-regulation of SLP-S, the truncated fragment of SIK3, in dorsal hippocampal neurons, restored the synaptic plasticity and alleviates the cognitive impairment in 5×FAD mice. Collectively, these findings revealed a novel and important role of SIK3-HDAC4 regulation of synaptic plasticity and propose a new target for therapeutic approaches of cognitive deficits associated with AD.

17.
Apoptosis ; 17(6): 600-11, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22434375

RESUMEN

Although caspases have been demonstrated to be involved in artemisinin (ARTE)-induced apoptosis, their exact functions are not well understood. The aim of this report is to explore the roles of caspase-8, -9 and -3 during ARTE-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cells. ARTE treatment induces a rapid generation of reactive oxygen species (ROS), and ROS-dependent apoptosis as well as the activation of caspase-8, -9 and -3 via time- and dose-dependent fashion. Of upmost importance, inhibition of caspase-8 or -9, but not caspase-3, almost completely blocks the ARTE-induced not only activation of the caspase-8, -9 and -3 but also apoptosis. In addition, the apoptotic process triggered by ARTE does not involve the Bid cleavage, tBid translocation, significant loss of mitochondrial membrane potential and cytochrome c release from mitochondria. Moreover, silencing Bax/Bak does not prevent the ATRE-induced cell death as well as the activation of caspase-8, -9 and -3. Collectively, our data firstly demonstrate that ARTE triggers a ROS-mediated positive feedback amplification activation loop between caspase-8 and -9 independent of mitochondria, which dominantly mediated the ARTE-induced apoptosis via a caspase-3-independent apoptotic pathway in ASTC-a-1 cells. Our findings imply a potential to develop new derivatives from artemisinin to effectively initiate the amplification activation loop of caspases.


Asunto(s)
Apoptosis/efectos de los fármacos , Artemisininas/farmacología , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Células/citología , Células/enzimología , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 8/genética , Caspasa 9/genética , Línea Celular Tumoral , Células/efectos de los fármacos , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Especies Reactivas de Oxígeno/metabolismo
18.
Sleep Breath ; 16(2): 329-40, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21347649

RESUMEN

PURPOSE: It is costly and time-consuming to conduct the standard manual titration to identify an effective pressure before continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) patients. Automatic titration is cheaper and more easily available than manual titration. The purpose of this systematic review was to evaluate the effect of automatic titration in identifying a pressure and on the improvement of apnea/hyponea index (AHI) and somnolence, the change of sleep quality, and the acceptance and compliance of CPAP treatment, compared with the manual titration. METHODS: A systematic search was made of the PubMed, EMBASE, Cochrane Library, SCI, China Academic Journals Full-text Databases, Chinese Biomedical Literature Database, Chinese Scientific Journals Databases and Chinese Medical Association Journals. Randomized controlled trials comparing automatic titration and manual titration were reviewed. Studies were pooled to yield odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). RESULTS: Ten trials involving 849 patients met the inclusion criteria. It is hard to identify a trend in the pressures determined by either automatic or manual titration. Automatic titration can improve the AHI (MD = 0.03/h, 95% CI = -4.48 to 4.53) and Epworth sleepiness scale (SMD = -0.02, 95% CI = -0.34 to 0.31,) as effectively as the manual titration. There is no difference between sleep architecture under automatic titration or manual titration. The acceptance of CPAP treatment (OR = 0.96, 95% CI = 0.60 to 1.55) and the compliance with treatment (MD = -0.04, 95% CI = -0.17 to 0.10) after automatic titration is not different from manual titration. CONCLUSION: Automatic titration is as effective as standard manual titration in improving AHI, somnolence while maintaining sleep quality similar to the standard method. In addition, automatic titration has the same effect on the acceptance and compliance of CPAP treatment as manual titration. With the potential advantage of time and cost savings, automatic titration was recommended to be applied in identifying a proper pressure for CPAP treatment instead of manual titration in clinical practice.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/métodos , Apnea Obstructiva del Sueño/terapia , Terapia Asistida por Computador/métodos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
19.
Respir Care ; 57(2): 238-43, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21762553

RESUMEN

BACKGROUND: CPAP is the first choice for most patients with obstructive sleep apnea (OSA), but the adherence to CPAP is suboptimal. The purpose of this study was to assess the adherence to CPAP therapy of Chinese OSA patients with CPAP therapy. METHODS: Two-hundred ten patients who had been diagnosed with OSA and had experienced CPAP titration trial as prescribed were enrolled in this study. Subjects were identified by reviewing our Snoring and Sleep Apnea Unit's records. The patients were interviewed by telephone and were asked to assess their CPAP use time. Those who said their CPAP use time was less than 4 h/d for 70% of the nights per week were questioned about their reasons for non-adherence. RESULTS: Seventeen patients were lost to follow-up. One-hundred ninety-three patients participated in our survey. Patient demographics included male/female (162/31), mean ± SD age (51.91 ± 10.10 y), and mean apnea-hypopnea index (59.99 ± 21.51 events/h). At the time of the interview (59 ± 32 months after initial titration trial), 100 of 193 patients (51.8%) were still using CPAP, 29 of 193 patients (15.0%) had abandoned CPAP after using it for a period, and 64 of 193 patients (33.2%) had never commenced therapy after titration. The most common reasons cited by the patients for the poor adherence were they were not able to acclimatize to the CPAP during the titration night, they did not perceive the need or the benefits of the treatment, or found it troublesome to use CPAP every night. CONCLUSIONS: The CPAP adherence is low in Tianjin, China. Only one half of these patients remained adherent to the treatment, and the other one half of these patients either never initiated the treatment or had abandoned CPAP use. To improve CPAP adherence, the medical staff should pay attention to making the titration trial a comfortable first CPAP experience for the patients. It is also very important to give the patients education and support about CPAP use in the follow-up, especially early on in this treatment.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Cooperación del Paciente/estadística & datos numéricos , Apnea Obstructiva del Sueño/terapia , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Ventiladores Mecánicos , Adulto , Anciano de 80 o más Años , China , Presión de las Vías Aéreas Positiva Contínua/instrumentación , Presión de las Vías Aéreas Positiva Contínua/métodos , Falla de Equipo/estadística & datos numéricos , Femenino , Servicios de Atención de Salud a Domicilio/organización & administración , Humanos , Entrevistas como Asunto , Masculino , Registros Médicos Orientados a Problemas/estadística & datos numéricos , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Satisfacción del Paciente/estadística & datos numéricos , Ventiladores Mecánicos/normas , Ventiladores Mecánicos/estadística & datos numéricos
20.
Health Soc Care Community ; 30(2): e305-e324, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34750910

RESUMEN

Caregivers of people with dementia (PwD) frequently experience poor physical, mental and social health. Over the past decade, several guidelines have offered recommendations on supporting caregivers to improve their health outcomes. This systematic review aimed to assess the quality and evidence base of guidelines on supporting caregivers of PwD and review the content of their recommendations on caregiver support to facilitate the adoption and implementation of a specific guideline among policymakers and practitioners. A systematic search for guidelines on supporting caregivers of PwD was performed using journal databases, websites of guideline development organisations and professional dementia-related societies from inception to 30 June 2020. Four independent reviewers performed the quality assessment of the included guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. A thematic synthesis was used to analyse the content of recommendations on caregiver support extracted from the included guidelines by two independent reviewers. The strength of recommendations and level of evidence were reclassified and analysed. Literature searches identified nine guidelines. Their quality was variable. The applicability domain on AGREE II yielded the lowest median score (62.2%; range: 18.6%-86.6%), suggesting that some guidelines lacked applicability in certain fields, leaving them open to interpretation. Most evidence underlying the extracted recommendations was rated as Levels 3 (51.3%) and 4 (31.1%). High-quality evidence is required to fortify these recommendations. The nine guidelines covered six themes-assessment, education, skill training, information provision, psychosocial support and general support policies-which can guide future policies and interventions of caregiver support. The recommendations extracted were consistent across guidelines, but each guideline failed to cover all six themes. Thus, more applicable and comprehensive guidelines that fully address all themes of support for caregivers of PwD are needed.


Asunto(s)
Cuidadores , Demencia , Cuidadores/psicología , Humanos
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