Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 272
Filtrar
1.
Talanta ; 209: 120509, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31891993

RESUMEN

One viable solution to improve the conformational stability of template proteins is to use multiple, weaker modes of action to immobilize proteins on the surfaces of a solid support. Herein, we introduce a novel surface imprinting technique for human serum albumin (HSA) by a dual immobilization/imprinting strategy. Specifically, HSA was first conjugated to the surfaces of magnetic Fe3O4 nanoparticles through a reversible aldmine condensation reaction. Dopamine (DA) was then used to imprint the protein template via an auto-polymerization reaction in biocompatible aqueous media. The resultant magnetic molecular imprinted polymers (MMIPs) possess high adsorption capacity (70.2 mg g-1), superior selectivity (IF = 4.54), and rapid capturing kinetics to HSA (within 20 min). We successfully demonstrate the practical applicability of MMIPs to the selective removal of HSA from human serum sample. Our work offers a novel and robust solution to develop proteins imprinted materials with high binding capacity and selectivity. We anticipate such materials will find wide applications to protein detection or removal in diverse real-life clinical and biological samples.

2.
Chin Med J (Engl) ; 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31996543

RESUMEN

BACKGROUND: In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension. METHODS: In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 µg norepinephrine (group N; n = 52) or 100 µg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well. RESULTS: Compared to group P, women in group N had a higher CO (standardized CO 5.8 ±â€Š0.9 vs. 5.3 ±â€Š1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ±â€Š17.2 vs. 60.0 ±â€Š13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ±â€Š174 vs. 996 ±â€Š182 dyne·s/cm, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ±â€Š11.6 vs. 75.0 ±â€Š7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05). CONCLUSIONS: Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

3.
Acta Biomater ; 101: 141-151, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31669696

RESUMEN

Recapitulating aligned cellular architectures of native tissues in vitro is important to engineer artificial tissue analogs with desired biological functions. Here a novel strategy is presented to direct three-dimensional (3D) cellular alignment by embedding cell/collagen hydrogel into the predefined electrohydrodynamically-printed microlattices. The cell/collagen hydrogel, originally filled within the printed microlattices uniformly, was found to gradually develop into densely-populated and highly-aligned bands along the longitudinal direction of the printed microlattices. The cellular alignment was highly dependent on the height, spacing and orientation of the microlattices. The presented method was applicable to multiple cell types including primary cardiomyocytes and the gaps formed between the aligned bands and the lateral walls of the microlattice facilitated the subsequent seeding and rapid alignment of other cell types which enables to engineer anisotropic multicellular tissue constructs. The engineered cardiac patches expressed mature cardiomyocyte-specific phenotypes and exhibited synchronous contractive activities. Multilayer cellular alignment with varied orientation in 3D collagen hydrogel was successfully achieved by using electrohydrodynamically-printed microlattices with layer-specific orientations. This exploration offers a promising way to engineer complex 3D tissue constructs with predefined cellular alignments. STATEMENT OF SIGNIFICANCE: Fabrication of biomimetic highly-aligned complex cellular architectures has a great significance to recapitulate the unique mechanical and physiological functions of the engineered tissues (e.g., heart tissue, neuron, muscle). Here, we introduced a novel strategy to direct 3D cellular alignment by embedding cell/collagen hydrogel into the predefined electrohydrodynamically-printed microlattices without any external stimuli. The microscopical study of the dynamic alignment process of cells and collagen fibers contributed to exploring the mechanism of autonomous formation of highly-aligned cellular bands. Multilayer cellular alignment with varied orientation in 3D collagen hydrogel was successfully achieved by using the microlattices with layer-specific orientations, which showed a promising way to engineer complex 3D tissue constructs with predefined cellular alignments.

4.
Medicine (Baltimore) ; 98(51): e18311, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31860981

RESUMEN

BACKGROUND: Studies have shown the efficacy of norepinephrine in the treatment of maternal hypotension during cesarean section by comparing it to treatment with phenylephrine. However, few studies have compared the efficacy of norepinephrine to ephedrine. METHODS: Ninety-seven women undergoing elective cesarean section were administered norepinephrine at 4 µg/minute (group N; n = 48) or ephedrine at 4 mg/minute (group E; n = 49) immediately postspinal anesthesia, with an on-off titration to maintain systolic blood pressure (SBP) at 80% to 120% of baseline. A rescue bolus of 8 µg norepinephrine was given whenever SBP reached the predefined lower limit. Our primary outcome was the incidence of tachycardia. Secondary outcomes included the incidence of bradycardia, hypertension, hypotension, severe hypotension, hypotensive episodes, number of rescue top-ups, hemodynamic performance error including median performance error (MDPE), and median absolute performance error (MDAPE). Neonatal Apgar scores and umbilical arterial (UA) blood gas data were also collected. RESULTS: Women in group N experienced fewer cases of tachycardia (4.2% vs 30.6%, P = .002, odds ratio: 0.11 [95% confidence interval, CI: 0.02-0.47]), a lower standardized heart rate (HR) (70.3 ±â€Š11 vs 75 ±â€Š11, P = .04, difference: 4.7 ±â€Š2.2 [95% CI: 0.24-9.1]), and a lower MDPE for HR (1.3 ±â€Š9.6 vs 8.4 ±â€Š13.5 bpm, P = .003, difference: 3.1 ±â€Š1.8 [95% CI: -0.6-6.7]). In addition, the lowest or the highest HR was lower in group N compared to group E (both P < .05). Meanwhile, the standardized SBP in group N was lower than that in group E (P = .04). For neonates, the UA blood gas showed a higher base excess (BE) and a lower lactate level in group N compared to E (both P < .001). Other hemodynamic variables, maternal, and neonatal outcomes were similar. CONCLUSION: Infusion of 4 µg/minute norepinephrine presented fewer cases of tachycardia, less fluctuation and a lower HR compared to baseline values, as well as a less stressed fetal status compared to ephedrine infusion at 4 mg/minute. In addition, norepinephrine infusion presented a lower standardized SBP compared to ephedrine.


Asunto(s)
Anestesia Raquidea/métodos , Cesárea/efectos adversos , Efedrina/uso terapéutico , Hipotensión/prevención & control , Norepinefrina/uso terapéutico , Adulto , Anestesia Raquidea/efectos adversos , Presión Sanguínea/efectos de los fármacos , Cesárea/métodos , Método Doble Ciego , Efedrina/efectos adversos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipotensión/etiología , Infusiones Intravenosas , Norepinefrina/administración & dosificación , Embarazo
5.
Front Neurol ; 10: 936, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31582958

RESUMEN

[This corrects the article DOI: 10.3389/fneur.2019.00347.].

6.
Opt Express ; 27(16): A1216-A1224, 2019 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-31510510

RESUMEN

It is documented that some unreasonable low real parts of aerosol complex refractive index (ACRI) are retrieved from measured particle optical properties, and whether the optically effective ACRI has a physically-based sense is still an open question. Numerical determination of the optically effective ACRI from accurately calculated scattering and absorption properties of polydisperse coated BC particles by the core-shell Mie, representing some internal-mixed aged BC particles under polluted urban environments, is performed with a Mie theory based data analysis scheme. After getting rid of retrieval uncertainties (such as altered shapes), the look-up tables without limiting ACRI ranges based on known particle compositions could theoretically result in some unreasonable extreme real parts of optically effective ACRI of coarse coated BC with some shell/core ratios. Based on limited look-up tables with aerosol compositions considered, the retrieved imaginary parts of optically effective ACRIs of coarse coated BC, showing smooth as a function of shell/core ratio, are significantly lower than those approximated by the volume weighted average (VWA) method by a factor of nearly 3. Although the VWA shows acceptable performances for coated BC in the Aitken or accumulation modes, it could overestimate the absorption of coarse coated BC by a factor of ~2 for large shell/core ratio. This may be one of the reasons why modelled aerosol optical depth is 20% larger than observed. Our study indicates that the optically effective ACRI of internal-mixed BC particles does have a physically-based meaning like real ACRI, unless limited ACRI look-up tables considering aerosol compositions are applied for retrieval. We suggest that the optically effective ACRI, rather than the ACRI given by the VWA, should be considered for coarse internal-mixed particles in the state-of-the-art aerosol-climate models.

7.
J Neurosci ; 39(43): 8576-8583, 2019 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-31527120

RESUMEN

Type 2 diabetes mellitus (T2DM) is a risk factor for the development of late-onset Alzheimer's disease (AD). However, the mechanism underlying the development of late-onset AD is largely unknown. Here we show that levels of the endothelial-enriched protein caveolin-1 (Cav-1) are reduced in the brains of T2DM patients compared with healthy aging, and inversely correlated with levels of ß-amyloid (Aß). Depletion of Cav-1 is recapitulated in the brains of db/db (Leprdb ) diabetic mice and corresponds with recognition memory deficits as well as the upregulation of amyloid precursor protein (APP), BACE-1, a trending increase in ß-amyloid Aß42/40 ratio and hyperphosphorylated tau (p-tau) species. Importantly, we show that restoration of Cav-1 levels in the brains of male db/db mice using adenovirus overexpressing Cav-1 (AAV-Cav-1) rescues learning and memory deficits and reduces pathology (i.e., APP, BACE-1 and p-tau levels). Knocking down Cav-1 using shRNA in HEK cells expressing the familial AD-linked APPswe mutant variant upregulates APP, APP carboxyl terminal fragments, and Aß levels. In turn, rescue of Cav-1 levels restores APP metabolism. Together, these results suggest that Cav-1 regulates APP metabolism, and that depletion of Cav-1 in T2DM promotes the amyloidogenic processing of APP and hyperphosphorylation of tau. This may suggest that depletion of Cav-1 in T2DM underlies, at least in part, the development of AD and imply that restoration of Cav-1 may be a therapeutic target for diabetic-associated sporadic AD.SIGNIFICANCE STATEMENT More than 95% of the Alzheimer's patients have the sporadic late-onset form (LOAD). The cause for late-onset Alzheimer's disease is unknown. Patients with Type 2 diabetes mellitus have considerably higher incidence of cognitive decline and AD compared with the general population, suggesting a common mechanism. Here we show that the expression of caveolin-1 (Cav-1) is reduced in the brain in Type 2 diabetes mellitus. In turn, reduced Cav-1 levels induce AD-associated neuropathology and learning and memory deficits. Restoration of Cav-1 levels rescues these deficits. This study unravels signals underlying LOAD and suggests that restoration of Cav-1 may be an effective therapeutic target.

8.
Nucleic Acids Res ; 47(17): 9358-9367, 2019 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-31392980

RESUMEN

Translation regulation plays an important role in eukaryotic gene expression. Upstream open reading frames (uORFs) are potent regulatory elements located in 5' mRNA transcript leaders. Translation of uORFs usually inhibit the translation of downstream main open reading frames, but some enhance expression. While a minority of uORFs encode conserved functional peptides, the coding regions of most uORFs are not conserved. Thus, the importance of uORF coding sequences on their regulatory functions remains largely unknown. We investigated the impact of an uORF coding region on gene regulation by assaying the functions of thousands of variants in the yeast YAP1 uORF. Varying uORF codons resulted in a wide range of functions, including repressing and enhancing expression of the downstream ORF. The presence of rare codons resulted in the most inhibitory YAP1 uORF variants. Inhibitory functions of such uORFs were abrogated by overexpression of complementary tRNA. Finally, regression analysis of our results indicated that both codon identity and position impact uORF function. Our results support a model in which a uORF coding sequence impacts its regulatory functions by altering the speed of uORF translation.


Asunto(s)
Biosíntesis de Proteínas , Procesamiento Proteico-Postraduccional/genética , ARN Mensajero/genética , Ribosomas/genética , Regiones no Traducidas 5'/genética , Codón/genética , Regulación de la Expresión Génica/genética , Sistemas de Lectura Abierta/genética , Secuencias Reguladoras de Ácidos Nucleicos/genética , Saccharomyces cerevisiae/genética
9.
Materials (Basel) ; 12(13)2019 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-31269737

RESUMEN

A theoretical model for the electrical conductivity size effect of square nanowires is proposed in this manuscript, which features combining the three main carrier scattering mechanisms in polycrystalline nanowires together, namely, background scattering, external surface scattering, as well as grain boundary scattering. Comparisons to traditional models and experiment data show that this model achieves a higher correlation with the experiment data.

10.
Int J Mol Sci ; 20(13)2019 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-31262079

RESUMEN

Hydrogen atom abstraction from propargyl C-H sites of alkynes plays a critical role in determining the reactivity of alkyne molecules and understanding the formation of soot precursors. This work reports a systematic theoretical study on the reaction mechanisms and rate constants for hydrogen abstraction reactions by hydrogen and hydroxy radicals from a series of alkyne molecules with different structural propargyl C-H atoms. Geometry optimizations and frequency calculations for all species are performed at M06-2X/cc-pVTZ level of theory and the hindered internal rotations are also treated at this level. The high-level W1BD and CCSD(T)/CBS theoretical calculations are used as a benchmark for a series of DFT calculations toward the selection of accurate DFT functionals for large reaction systems in this work. Based on the quantum chemistry calculations, rate constants are computed using the canonical transition state theory with tunneling correction and the treatment of internal rotations. The effects of the structure and reaction site on the energy barriers and rate constants are examined systematically. To the best of our knowledge, this work provides the first systematic study for one of the key initiation abstraction reactions for compounds containing propargyl hydrogen atoms.


Asunto(s)
Alquinos/química , Propanoles/química , Hidrógeno/química
11.
Org Lett ; 21(16): 6383-6387, 2019 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-31356086

RESUMEN

A cascade alkynylation and selective hydrogenation catalyzed by covalent binaphthyl-stabilized palladium nanoparticles has been established, providing a novel and highly efficient methodology for accessing Z and Z,Z-selective phosphinyl [3]dendralenes with broad functional group tolerance and good yields. This strategy achieves the first cascade reactions of alkynylation and hydrogenation with chemoselectivity modulated by catalyst loading.

12.
Zhen Ci Yan Jiu ; 44(5): 388-91, 2019 May 25.
Artículo en Chino | MEDLINE | ID: mdl-31155875

RESUMEN

Acupuncture is widely used in the treatment of ischemic diseases of the central nervous system in different clinical stages and has achieved a good clinical effect. The current research showed that acupuncture can improve cerebral blood flow perfusion via increasing blood flow volume, blood flow velocity, the levels of vasomotor substances and reduction of blood viscosity and erythrocyte aggregation index. In recent years, many studies focused on the pathophysiological mechanism of acupuncture in improving cerebral ischemia via triggering the cholinergic vasodilatation, up-regulation of expression of vascular-related proteins and genes,attenuation of inflammatory reaction, etc. Currently, the methods for evaluating the effect of acupuncture are mostly noninvasive functional magnetic resonance imaging in healthy subjects. Future studies should include united selection of acupoints and acupuncture needle manipulations, more reasonable combination of different acupoints, united outcome evaluative standards, better repeatability, employment of big data, etc.


Asunto(s)
Terapia por Acupuntura , Isquemia Encefálica , Isquemia Encefálica/terapia , Humanos , Hipoxia
13.
Arch Oral Biol ; 104: 60-66, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31174095

RESUMEN

OBJECTIVES: Beneficial effects of low-intensity pulsed ultrasound(US) have been reported for knee articular cartilage injury. It is unclear whether the same effect could be observed on mandibular condylar cartilage. This study was designed to explore the efficacy of ultrasound cartilage repair via autophagy regulation. METHODS: A total of 18 adult rabbits were divided into a sham operation group (exposure to condylar articular surface only), operation without US group (only cartilage surgery), and operation with US group (received ultrasonic therapy daily on day 4 after cartilage surgery). The rabbits were then sacrificed to construct a temporomandibular joint (TMJ) cartilage injury model and HE staining was conducted to observe pathological changes of cartilage in each group. Expression of FGF18, FGFR4, beclin1, ATG3 and ATG7 in rabbit TMJ cartilage were detected using RT-PCR and western blotting. Finally, protein-protein interaction (PPI) analysis was used to observe the interaction among the network of important biomarkers in this injury model. RESULTS: Compared to the operation without US group, the severity of cartilage injury was decreased in the operation with US group according to HE staining. The expression of autophagy biomarkers, beclin1, ATG3, ATG7, FGF18 and FGFR4, in operation with US group were up-regulated compared with those in sham operation group and operation without US group p < 0.05). In PPI analysis, ATG3, ATG7, PIK3C3, PIK3R4, BECN1 were identified as hub nodes connecting with most proteins network. CONCLUSIONS: Our results suggest US has therapeutic potential for the treatment of mandibular condylar cartilage injury, and may affect chondrocyte autophagy.


Asunto(s)
Cartílago Articular , Ondas Ultrasónicas , Animales , Cartílago Articular/lesiones , Condrocitos , Cóndilo Mandibular , Conejos , Articulación Temporomandibular
14.
Biomed Pharmacother ; 117: 109088, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31202173

RESUMEN

The acute kidney injury(AKI) caused by nephrotoxic drugs contributes to inflammation and oxidative injury in podocytes. Wedelolactone (WED), a natural compound, is found with activities as anti-inflammation, anti-oxidative, anti-free radical,and etc. In this present study, MPC-5 cells were exposed to the nephrotoxic drugs doxorubicin (DOX). The results showed that WED significantly increased the SOD activity, CAT and GSH-Px levels, while significantly decreased the MDA content and ROS levels in DOX-induced MPC-5 cells. WED could also significantly decrease the levels of cytokines IL-6, MCP-1, TNF-α, and TGF-ß1. Additionally, the activation and phosphorylation of IκKα, IκBα and NF-κB p65 was inhibited by WED. The co-treatment of PDTC (NF-κB inhibitor) and WED significantly reduced NF-κB p65 phosphorylation. These findings suggested that WED alleviated inflammation and oxidative stress of doxorubicin-induced MPC-5 cells through IκK/IκB/NF-κB signaling pathway.


Asunto(s)
Cumarinas/farmacología , Doxorrubicina/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Podocitos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Línea Celular , Proteínas I-kappa B/metabolismo , Inflamación/metabolismo , Ratones , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Podocitos/metabolismo , Ratas , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
15.
Nat Commun ; 10(1): 2716, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31221978

RESUMEN

Catalytic asymmetric cycloadditions via transition-metal-containing dipolar intermediates are a powerful tool for synthesizing chiral heterocycles. However, within the field of palladium catalysis, compared with the well-developed normal electron-demand cycloadditions with electrophilic dipolarophiles, a general strategy for inverse electron-demand ones with nucleophilic dipolarophiles remains elusive, due to the inherent linear selectivity in the key palladium-catalyzed intermolecular allylations. Herein, based on the switched regioselectivity of iridium-catalyzed allylations, we achieved two asymmetric [4+2] cycloadditions of vinyl aminoalcohols with aldehydes and ß,γ-unsaturated ketones through synergetic iridium and amine catalysis. The activation of vinyl aminoalcohols by iridium catalysts and carbonyls by amine catalysts provide a foundation for the subsequent asymmetric [4+2] cycloadditions of the resulting iridium-containing 1,4-dipoles and (di)enamine dipolarophiles. The former provides a straightforward route to a diverse set of enantio-enriched hydroquinolines bearing chiral quaternary stereocenters, and the later represent an enantio- and diastereodivergent synthesis of chiral hydroquinolines.

16.
J Adv Nurs ; 75(8): 1805-1814, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31037755

RESUMEN

AIM: To describe a protocol that examines the feasibility and effectiveness of a face-to-face guided self-disclosure intervention for facilitating benefit finding and other related psychological outcomes for breast cancer patients. BACKGROUND: Benefit finding can promote a positive attitude among patients facing disease. However, limited studies have focused on improving benefit finding among breast cancer patients. Previous research has been based on group interventions, which may not suit all patients. Self-disclosure was recognized as a strong predictor of benefit finding. This protocol is based on a brief face-to-face disclosure intervention to improve benefit finding for breast cancer patients. DESIGN: A non-blinded randomized controlled trial. METHODS: A total of 154 patients with breast cancer who have undergone radical mastectomy will be randomly assigned to either the experimental group, which will participate in a six-session face-to-face individual intervention, or the control group at a ratio of 1:1. Baseline assessments will take place after the breast cancer diagnosis, with follow-up assessments at 3, 6 and 9 months after baseline. The primary outcome is benefit finding; other outcomes are self-disclosure, cognitive reappraisal, social support, optimism and medical coping modes. DISCUSSION: This study is to design a protocol for guided self-disclosure interventions to promote benefit finding in Chinese breast cancer patients. If this intervention is feasible and effective, it could be implemented in clinical practice. IMPACT: This study will provide useful advice for health professionals to guide breast cancer patients in benefit finding during stressful events. If it is effective, it will be implemented broadly in clinical practice.


Asunto(s)
Adaptación Psicológica , Grupo de Ascendencia Continental Asiática/psicología , Neoplasias de la Mama/psicología , Revelación , Sobrevivientes/psicología , Adolescente , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven
17.
Front Neurol ; 10: 347, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31105631

RESUMEN

Leigh syndrome (LS) is a mitochondrial disease of infancy and early childhood, that is rarely seen in adults. The high degree of genetic and clinical heterogeneity makes LS a very complex syndrome. The clinical manifestations include neurological symptoms and various non-neurological symptoms, with different mutations differing in presentations and therapies. The m.10191T>C mutation in the mitochondrial DNA gene encoding in the respiratory chain complex I (CI) subunit of MTND3 results in the substitution of a highly conserved amino acid (p.Ser45Pro) within the ND3 protein, leading to CI dysfunction and causing a broad clinical spectrum of disorders that includes LS. Patients with the m.10191T>C mutation are rare in general, even more so in adults. In the present study, we report a family of patients with very rare adult-onset Leigh-like syndrome with the m.10191T>C mutation. The 24-year-old proband presented with seizures 6 years ago and developed refractory status epilepticus on admission. She had acute encephalopathy accompanied by lactic acidosis, symmetrical putamen and scattered cortical lesions. The video electroencephalogram suggested focal-onset seizures. She harbored the heteroplasmic m.10191T>C mutation in her blood and fibroblasts. Her aunt was diagnosed with mitochondrial disease at the age of 42, and had the heteroplasmic m.10191T>C mutation in her fibroblasts. Her aunt's son (cousin) died of respiratory failure at the age of 8, and we suspected he was also a case of LS. Furthermore, we reviewed the previously reported patients with the m.10191T>C mutation and summarized their characteristics. Recognizing the characteristics of these patients will help us improve the clinical understanding of LS or Leigh-like syndrome.

18.
Biomed Res Int ; 2019: 7505260, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31032362

RESUMEN

Background: Repeated or continuous chronic psychological stress may induce diverse neuropsychiatric disorders; however, the underlying mechanisms remain unclear. In this study, we explored the expression profiles of long noncoding RNAs (lncRNAs) and mRNAs, along with their biological function and regulatory network, in mice after repeated social defeat (RSD) stress to explore their potential involvement in the development of anxiety-like behaviors. Main Methods: RNA-sequencing was used to screen all differentially expressed (DE) lncRNAs and mRNAs between the RSD and control groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for confirmation of the RNA-sequencing results. The function of DE lncRNAs was predicted by Gene Ontology (GO) enrichment and pathway analyses of target mRNAs. In addition, the functional regulatory network of the target mRNAs was constructed to reveal potential relationships between lncRNAs and their target genes with bioinformatics approaches. Key Findings: In mice experiencing RSD, 373 and 454 lncRNAs, along with 1142 and 654, mRNAs were significantly upregulated and downregulated, respectively. The detailed regulatory network included 126 eligible lncRNA-mRNA pairs. Among them, 14 genes such as Arhgef1, Chchd2, Fam107a, Dlg1, Nova2, Dpf1, and Shank3 involved in neurite growth, neural development, and synaptic plasticity were direct targets of the DE lncRNAs. qRT-PCR of four of the DE lncRNAs and mRNAs confirmed the reliability of RNA-sequencing. GO clustering analyses showed that the top enriched biological process, cellular component, and molecular function terms were synaptic transmission, neuron spine, and glutamate receptor binding, respectively. Further, the top three significant enriched pathways were synaptic adhesion-like molecule (SALM) protein interactions at the synapses, trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as glutamate binding, activation of AMPA receptors, and synaptic plasticity. Significance: Hundreds of lncRNAs and mRNAs are dysregulated after RSD, and many of these lncRNAs might participate in the development of anxiety-like behaviors via multiple complex mechanisms such as target regulation. Available informatics evidence highlighted the likely role of synapse dysfunction and abnormal synaptic neurotransmission in these behaviors. Thus, our findings provide potential candidate biomarkers or intervention targets for chronic psychological stress-induced neuropsychiatric disorders.


Asunto(s)
Corteza Prefrontal/metabolismo , ARN Largo no Codificante/genética , Estrés Psicológico/genética , Animales , Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes/genética , Humanos , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Corteza Prefrontal/fisiopatología , ARN Mensajero/genética , Análisis de Secuencia de ARN , Estrés Psicológico/fisiopatología
19.
Arterioscler Thromb Vasc Biol ; 39(6): 1191-1202, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30943774

RESUMEN

Objective- To determine whether pulmonary arterial hypertension is associated with endothelial cell (EC)-Cav-1 (caveolin-1) depletion, EC-derived extracellular vesicle cross talk with macrophages, and proliferation of Cav-1 depleted ECs via TGF-ß (transforming growth factor-ß) signaling. Approach and Results- Pulmonary vascular disease was induced in Sprague-Dawley rats by exposure to a single injection of VEGFRII (vascular endothelial growth factor receptor II) antagonist SU5416 (Su) followed by hypoxia (Hx) plus normoxia (4 weeks each-HxSu model) and in WT (wild type; Tie2.Cre-; Cav1 lox/lox) and EC- Cav1-/- (Tie2.Cre+; Cav1 fl/fl) mice (Hx: 4 weeks). We observed reduced lung Cav-1 expression in the HxSu rat model in association with increased Cav-1+ extracellular vesicle shedding into the circulation. Whereas WT mice exposed to hypoxia exhibited increased right ventricular systolic pressure and pulmonary microvascular thickening compared with the group maintained in normoxia, the remodeling was further increased in EC- Cav1-/- mice indicating EC Cav-1 expression protects against hypoxia-induced pulmonary hypertension. Depletion of EC Cav-1 was associated with reduced BMPRII (bone morphogenetic protein receptor II) expression, increased macrophage-dependent TGF-ß production, and activation of pSMAD2/3 signaling in the lung. In vitro, in the absence of Cav-1, eNOS (endothelial NO synthase) dysfunction was implicated in the mechanism of EC phenotype switching. Finally, reduced expression of EC Cav-1 in lung histological sections from human pulmonary arterial hypertension donors was associated with increased plasma concentration of Cav-1, extracellular vesicles, and TGF-ß, indicating Cav-1 may be a plasma biomarker of vascular injury and key determinant of TGF-ß-induced pulmonary vascular remodeling. Conclusions- EC Cav-1 depletion occurs, in part, via Cav-1+ extracellular vesicle shedding into the circulation, which contributes to increased TGF-ß signaling, EC proliferation, vascular remodeling, and pulmonary arterial hypertension.

20.
Am J Transl Res ; 11(2): 721-732, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30899374

RESUMEN

There are increasing invasive fungal infections associated with non-albicans, which causes mortal infections in immune deficiency population. Candida krusei is a major non-albicans that exhibits intrinsic resistance to fluconazole and makes clinical treatment difficult. Previous studies revealed that C-type lectin receptors (CLRs) Dectin-1 plays critical roles in host defense against C. albicans infections. C. krusei and C. albicans are phylogenetically different although in the same genus. Whether Dectin-1 contributes to host immune response against C. krusei infection is still unknown. In the present study, we explored the potential roles of the Dectin-1 in host defense against C. krusei. We found that Dectin-1 ligand ß-(1,3)-glucan markedly exposed on the cell surface of C. krusei, while ß-(1,3)-glucan of C. albicans is masked. Dectin-1 is required for host myeloid cells recognition, killing of C. krusei, and development of subsequent Th1 and Th17 cell-mediated adaptive immune response. Furthermore, Dectin-1-deficient mice (Dectin-1-/- ) are more susceptible to C. krusei infection. Together, we confirmed the important roles of Dectin-1 in host defense against C. krusei infection, demonstrating a previously unknown mechanism for C. krusei infection. Our study, therefore, provides a further understanding of host immune response against C. krusei.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA