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1.
Perfusion ; : 2676591231194454, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658740

RESUMO

BACKGROUND: The perioperative outcomes following off-pump multi-vessel minimally invasive surgery (MICS) coronary artery bypass grafting (CABG) via a single left intercostal space incision has not been well evaluated. METHOD: From July 2019 to January 2022, a total of 444 patients with multi-vessel coronary artery disease (CAD) were enrolled and divided into MICS (n = 179) and sternotomy CABG (n = 265). Perioperative outcomes were compared between these two groups, including intraoperative blood loss, postoperative first 24 h drainage, ventilation duration, length of stay (LOS) in ICU and total LOS in hospital. Intraoperative blood flow of graft vessels were measured by transit-time flow measurement after vascular anastomosis and mean flow (MF) and pulsatile index (PI) were compared. RESULTS: There were no significant differences in preoperative profiles between these two groups except younger and lower proportion of female in MICS. No significant difference in the number of graft vessels was observed between MICS (3.18 ± 0.74) and sternotomy CABG (3.28 ± 0.86). Compared to sternotomy CABG, patients with MICS showed longer operation duration [(4.33 ± 0.86) h versus (5.10 ± 1.09) h], fewer intraoperative blood loss [700 (600, 900) mL versus 500 (200, 700) mL], fewer postoperative first 24 h drainage [400 (250, 500) mL versus 300 (200, 400) mL], shorter postoperative ventilation duration [16.5 (12.5, 19.0) h versus 15.0 (12.0, 17.0) h], LOS in ICU [20.0 (16.0, 23.0) h versus 18.0 (15.0, 20.0) h] and total LOS in hospital [(14.5 ± 3.9) d versus (12.6 ± 2.7) d] (all p < .001). MI and PI of graft vessels were similar and no significant differences in major perioperative complications and mortality were observed between MICS and sternotomy CABG (all p > .05). CONCLUSION: Off-pump multi-vessel MICS may be an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes than sternotomy CABG.

2.
Cell Death Dis ; 14(8): 570, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37640747

RESUMO

Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.


Assuntos
Lesões por Esmagamento , Traumatismos do Nervo Óptico , Traumatismos dos Nervos Periféricos , Animais , Camundongos , Traumatismos do Nervo Óptico/genética , Axônios , Regeneração Nervosa , Retina , Nervo Óptico , Células Ganglionares da Retina , Lesões por Esmagamento/genética
3.
J Plant Physiol ; 280: 153904, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36566672

RESUMO

Blue light can regulate the photomorphogenesis of plants through blue light receptors to influence seedling growth and development. The COP9 signaling complex (CSN), a vital regulator of photomorphogenesis, is a highly conserved protein complex. CSN1 is the largest and most critical subunit in the CSN with a complex N-terminal function that supports most of the functions of CSN1 and is mainly involved in plant growth and development processes. The CSN is also required in the blue light-mediated photomorphogenesis response of seedlings. In this study, the OsCSN1 subunit of Oryza sativa subsp. japonica (rice) was edited and screened, and OsCSN1 deletion mutant, OsCSN1 weak expression mutant and OsCSN1 overexpression mutant were constructed. The mechanism of OsCSN1 and its N-terminal effects on rice seedling growth and development under blue light conditions were investigated. The addition of exogenous hormone gibberellin (GA3) and gibberellin synthesis inhibitor paclobutrazol (PAC) caused aboveground phenotypic and protein (such as CUL4 and SLR1) changes. Blue light regulates the degradation of SLR1 through OsCSN1, which regulates the growth and development of rice seedling height, the first incomplete leaf, and the coleoptile. It is hypothesized that rice affects CRY-COP1 interactions after sensing blue light signals through the cryptochrome, and the nuclear localization of COP1 is regulated by the CSN complex. OsCSN1 is a negative regulator in response to blue light. The core structural domain of action that inhibits the growth of the aboveground part of rice seedlings is located at the N-terminal of OsCSN1. OsCSN1 regulates the nuclear localization of COP1 through the COP9 signaling complex and degrades SLR1 through CUL4-based E3 ligase. Ultimately, it affects the synthesis of the endogenous hormone GA, thereby inhibiting the aboveground growth and development of rice seedlings.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Oryza , Plântula/metabolismo , Proteínas de Arabidopsis/metabolismo , Oryza/metabolismo , Arabidopsis/metabolismo , Giberelinas/metabolismo , Luz , Transdução de Sinais , Hormônios/metabolismo , Hormônios/farmacologia , Regulação da Expressão Gênica de Plantas
4.
Toxicol In Vitro ; 78: 105252, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34624480

RESUMO

The ability of ten polyphenolic antioxidants to prevent CuO nanoparticle (NPCuO) and H2O2-mediated DNA damage and cytotoxicity was investigated. Five of the polyphenols (MEPCA, PREGA, MEGA, ECG, and EGCG) prevent NPCuO/H2O2-mediated DNA damage (IC50 values of 7.5-800 µM), three have no effect (PCA, VA, and EC), and two (GA and EGC) result in increased DNA damage. Most polyphenols had similar antioxidant/prooxidant activity in the presence of NPCuO or free copper ions. Electron paramagnetic resonance (EPR) spectroscopy of reactive oxygen species (ROS) generated by NPCuO/H2O2 in the presence of representative polyphenols correlate with results of DNA damage studies: in the presence of NPCuO/H2O2, MEPCA prevents ROS formation, VA has no effect on ROS levels, and EGC increases ROS levels. EPR results with CuO nanoparticles washed to remove dissolved copper in solution (wCuO) in the presence of H2O2/ascorbate suggest that MEPCA prevents ROS formation on the nanoparticle surface in addition to preventing ROS formation from dissolved copper. In mouse fibroblast (L929) cells, combining NPCuO with H2O2 results in significantly greater cytotoxicity than observed for either component alone. After 3 h incubation with MEPCA or MEGA, the viability loss in L929 cells induced by NPCuO/H2O2 challenge was significantly rescued at physiologically relevant polyphenol levels (1 µM). These studies show that polyphenols can protect DNA and inhibit cytotoxicity generated by NPCuO under oxidative stress conditions.


Assuntos
Cobre/toxicidade , Nanopartículas Metálicas/toxicidade , Polifenóis/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Camundongos , Espécies Reativas de Oxigênio/metabolismo
5.
Nanomaterials (Basel) ; 11(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684906

RESUMO

We have previously demonstrated that iron oxide nanoparticles with dopamine-anchored heterobifunctional polyethylene oxide (PEO) polymer, namely PEO-IONPs, and bio-functionalized with sialic-acid specific glycoconjugate moiety (Neu5Ac(α2-3)Gal(ß1-4)-Glcß-sp), namely GM3-IONPs, can be effectively used as antibacterial agents against target Escherichia coli. In this study, we evaluated the biocompatibility of PEO-IONPs and GM3-IONPs in a normal human colon cell line CCD-18Co via measuring cell proliferation, membrane integrity, and intracellular adenosine triphosphate (ATP), glutathione GSH, dihydrorhodamine (DHR) 123, and caspase 3/7 levels. PEO-IONPs caused a significant decrease in cell viability at concentrations above 100 µg/mL whereas GM3-IONPs did not cause a significant decrease in cell viability even at the highest dose of 500 µg/mL. The ATP synthase activity of CCD-18Co was significantly diminished in the presence of PEO-IONPs but not GM3-IONPs. PEO-IONPs also compromised the membrane integrity of CCD-18Co. In contrast, cells exposed to GM3-IONPs showed significantly different cell morphology, but with no apparent membrane damage. The interaction of PEO-IONPs or GM3-IONPs with CCD-18Co resulted in a substantial decrease in the intracellular GSH levels in a time- and concentration-dependent manner. Conversely, levels of DHR-123 increased with IONP concentrations. Levels of caspase 3/7 proteins were found to be significantly elevated in cells exposed to PEO-IONPs. Based on the results, we assume GM3-IONPs to be biocompatible with CCD-18Co and could be further evaluated for selective killing of pathogens in vivo.

6.
Front Surg ; 7: 590956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195392

RESUMO

Background: Primary squamous cell carcinoma of the thyroid (PSCCT) is an uncommon malignancy that is difficult to diagnose and differentiate. There is no consensus for the early clinical, radiological, or ultrasonic identification of PSCCT before pathological changes are observed in patients. There is also no suitable treatment due to the absence of a definite diagnosis. Case Presentation: A 76-year-old female patient complained about a rapidly growing cervical mass, dyspnea, dysphagia, and a change in her voice. Based on the results of thyroid ultrasound, fine-needle aspiration, and plain and enhanced CT, the patient was initially diagnosed with anaplastic thyroid carcinoma (ATC). Thereafter, we removed the mass that was the patient's main complaint. The gross examination of the patient's symptoms also supported our previous diagnosis. However, her disease was finally diagnosed as PSCCT, according to the histopathology and immunohistochemistry findings of the mass. Conclusion: Our case highlights the need for a comprehensive framework in the management of PSCCT. The more auxiliary examinations (e.g., ultrasonographic, radiology, or biopsy examinations) we take, the more likely we are to identify this disease. Immunohistochemistry is currently the preferred examination for the diagnosis of PSCCT, while surgical resection combined with radio-sensitizing therapy and adjuvant chemotherapy is the main treatment method for PSCCT.

7.
Front Oncol ; 10: 1291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850401

RESUMO

Purpose: The aim of this study was to review the clinicopathologic characteristics, treatments, and outcomes of patients with primary large cell neuroendocrine carcinoma of the bladder (LCNEC). Patients and Methods: We report one patient diagnosed with primary pure LCNEC of the bladder in Sun Yat-sen Memorial Hospital. In addition, we performed a systematic literature review, in April 2020, on case report and case series of LCNEC of the bladder. The clinicopathologic characteristics, treatments and outcomes of this rare disease were analyzed. Results: A total of 39 patients were included in our analysis (1 case from our institution and 38 cases from the literature). Most patients (79.5%) were male. The average age at the surgery for the patients is 61.5 years (range 19-85 years). The most common symptom was hematuria (n = 20, 76.9%). Almost all patients (38, 97.4%) underwent surgery, with 26 (66.7%) receiving multimodality therapy. Out of 24 patients with available data, regional or distant recurrences developed in 14 patients (58.3%). The median overall survival of the patients was 11.5 months, with 1- and 3-year survival rates of 54.0 and 21.4%, respectively. In the survival analysis, theT1-2 tumors (P = 0.025), no distant metastases at diagnosis (P = 0.001), and multimodality therapy (P = 0.017) were associated with better overall survival (OS). Conclusions: LCNEC of the bladder is an extremely rare neoplasm. The available data suggest that the disease has an aggressive natural history with poor prognosis. Early pathologic stage and multimodality treatment may be important factors in determining prognosis.

8.
Front Oncol ; 10: 975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676454

RESUMO

Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.

9.
Nanoscale ; 12(27): 14724-14732, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32618977

RESUMO

A unique technique to passivate both bottom and top sides of perovskite has been successfully developed to achieve highly efficient inverted perovskite light-emitting diodes (PeLEDs). For the bottom passivation, an organic/inorganic hybrid electron transporting layer (ETL) replaces the widely adopted inorganic ETL to overcome the disadvantages of the pure inorganic ETL. The ZPM (ZnO-in-polymer matrix) ETL, which consists of ZnO nanoparticles blended into polyvinylpyrrolidone, not only passivates the surface defects of ZnO nanoparticles, but also improves the morphology and stability of FAPbBr3 film. For the top passivation, smaller grains and a FAPbBr3/PEA2PbBr4 3D/2D hybrid structure are obtained by applying a small amount of PEABr solution. The synergetic interplay of organic/inorganic hybrid ETL and organic halide salt surface modification substantially shrinks the grain size to facilitate radiative recombination, and suppresses non-radiative recombination both at the interface of ETL/perovskite and HTL/perovskite, and in the perovskite layer. As a result, the highly efficient green PeLED sets a new record of device performance for FAPbBr3-based inverted PeLEDs, with current efficiency of 39.7 cd A-1, external quantum efficiency of 9.0%, power efficiency of 46.4 lm W-1, maximum luminance of 6.03 × 104 cd m-2, and half-lifetime of 297 minutes at an initial brightness of ∼100 cd m-2.

10.
J Nanosci Nanotechnol ; 20(9): 5874-5884, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32331193

RESUMO

In order to achieve the effective removal of Pb2+ from low-concentration wastewater as well as the lead recovery for direct reuse simultaneously, a simple electrodeposition method was used in this study. In this process, synthetic lead wastewater with low concentration of 4, 8, 12 and 16 mg/L was treated, more than 67% lead was recovered from wastewater and a PbO2/Ti electrode was fabricated in a simple reaction tank. The test results of characterizations confirmed that PbO2 nanoeletrocatalyst was successfully deposited on a Ti substrate. Electrochemical activity tests indicated that PbO2/Ti electrode had advantages of high oxygen evolution potential (1.90 V) and low electron transfer resistance. Furthermore, the results of electrocatalytic degradation experiments demonstrated that prepared PbO2/Ti electrode had the superb decolorization and mineralization ability on Basic Red. After 120 min of electrolysis, the Basic Red removal efficiency and TOC removal efficiency could reach to 89.38% and 68.82%, respectively, which was 5.2 and 7.1 times higher than the Ti substrate alone. Besides, the calculated mineralization current efficiency for PbO2/Ti electrode increased from 5.18% to 36.74% after PbO2 depositing, and thus an economical benefit was obtained by more than 5 times energy saving. The influences of the applied current density, initial dye concentration, electrolyte concentration and solution pH on the oxidation efficiency were also investigated and optimized. The prepared PbO2/Ti electrode also showed a great stability with high dye removal efficiency (above 85%) after 10 times repeated experiments. These results suggest that it is a promising technological process to remove and recover lead from low-concentration wastewater efficiently and reuse them as electrocatalyst for other organic wastewater treatments.

11.
Front Neurol ; 11: 81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161563

RESUMO

Paroxysmal sympathetic hyperactivity (PSH) has predominantly been described after traumatic brain injury (TBI), which is associated with hyperthermia, hypertension, tachycardia, tachypnea, diaphoresis, dystonia (hypertonia or spasticity), and even motor features such as extensor/flexion posturing. Despite the pathophysiology of PSH not being completely understood, most researchers gradually agree that PSH is driven by the loss of the inhibition of excitation in the sympathetic nervous system without parasympathetic involvement. Recently, advances in the clinical and diagnostic features of PSH in TBI patients have reached a broad clinical consensus in many neurology departments. These advances should provide a more unanimous foundation for the systematic research on this clinical syndrome and its clear management. Clinically, a great deal of attention has been paid to the definition and diagnostic criteria, epidemiology and pathophysiology, symptomatic treatment, and prevention and control of secondary brain injury of PSH in TBI patients. Potential benefits of treatment for PSH may result from the three main goals: eliminating predisposing causes, mitigating excessive sympathetic outflow, and supportive therapy. However, individual pathophysiological differences, therapeutic responses and outcomes, and precision medicine approaches to PSH management are varied and inconsistent between studies. Further, many potential therapeutic drugs might suppress manifestations of PSH in the process of TBI treatment. The purpose of this review is to present current and comprehensive studies of the identification of PSH after TBI in the early stage and provide a framework for symptomatic management of TBI patients with PSH.

12.
Microorganisms ; 8(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143469

RESUMO

The growth of a large number of poisonous plants is an indicator of grassland degradation. Releasing allelochemicals through root exudates is one of the strategies with which poisonous plants affect neighboring plants in nature. Arbuscular mycorrhizal fungi (AMF) can form a mutualistic symbiosis with most of the higher plants. However, the manner of interaction between root exudates of poisonous plants and AMF on neighboring herbage in grasslands remains poorly understood. Stellera chamaejasme L., a common poisonous plant with approved allelopathy, is widely distributed with the dominant grass of Leymus chinensis in the degradeds of Northern China. In this study, we investigated the addition of S. chamaejasme root exudates (SRE), the inoculation of AMF, and their interaction on the growth and tissue nitrogen contents of L. chinensis, the characteristics of rhizosphere AMF, and soil physicochemical properties. Results showed that SRE had significant effects on ramet number, aboveground biomass, and total nitrogen of L. chinensis in a concentration dependent manner. Additionally, SRE had a significant negative effect on the rate of mycorrhiza infection and spore density of the AMF. Meanwhile, the addition of SRE significantly affected soil pH, electrical conductivity, available nitrogen (AN), available phosphorus (AP), total nitrogen (TN), and total carbon (TC) contents; while neither inoculation of AMF itself nor the interaction of AMF with SRE significantly affected the growth of L. chinensis. The interaction between AMF and SRE dramatically changed the pH, AP, and TC of rhizosphere soil. Therefore, we suggested SRE of S. chamaejasme affected the growth of L. chinensis by altering soil pH and nutrient availability. AMF could change the effect of SRE on soil nutrients and have the potential to regulate the allelopathic effects of S. chamaejasme and the interspecific interaction between the two plant species. We have provided new evidence for the allelopathic mechanism of S. chamaejasme and the regulation effects of AMF on the interspecific relationship between poisonous plants and neighboring plants. Our findings reveal the complex interplay between the root exudates of poisonous plants and rhizosphere AMF in regulating population growth and dynamics of neighboring plants in degraded grassland ecosystems.

13.
Br J Neurosurg ; 34(3): 284-289, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32090624

RESUMO

Background: Pneumocephalus is a common finding after burr-hole drainage of chronic subdural hematoma (CSDH). Its effects have not been specifically studied.Methods: A retrospective analysis was performed in 140 patients with CSDH with single burr-hole drainage. The pre- and postoperative volumes of intracranial hematoma and the postoperative volume of pneumocephalus were calculated and analyzed with their relationships with Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores.Results: The preoperative hematoma volume and the patient ages are positively correlated with the 1-day postoperative pneumocephalus volume (p < 0.001, p < 0.01). There is no correlation between postoperative pneumocephalus volume and GCS/GOS scores (p > 0.05) and there is no difference of GCS/GOS scores or CSDH recurrence rate between patients with and without pneumocephalus (p > 0.05). The age and the volume of 1-day postoperative pneumocephalus are positively correlated with the absorbing rate of pneumocephalus (p < 0.01, p < 0.001).Conclusions: The pneumocephalus at a certain range has no effect on the prognosis of patients with CSDH and requires no specific intervention due to its self-absorbing capacity in the normal progress after surgery.HighlightsNo correlation between postoperative pneumocephalus volume and GCS/GOS scores.No difference of GCS/GOS or recurrence between patients with pneumocephalus or not.Pneumocephalus at certain range has no effect on the prognosis of patients.


Assuntos
Hematoma Subdural Crônico , Pneumocefalia , Drenagem , Hematoma Subdural Crônico/cirurgia , Humanos , Pacientes , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Trepanação
14.
J Cell Biochem ; 120(9): 15776-15789, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31074048

RESUMO

Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival-related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival-related genes in the hippocampus by using real-time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.


Assuntos
Lesões Encefálicas Traumáticas/genética , Perfilação da Expressão Gênica/métodos , Receptores Purinérgicos P2X3/genética , Receptores Purinérgicos P2X3/metabolismo , Animais , Lesões Encefálicas Traumáticas/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Sprague-Dawley , Regulação para Cima
15.
J Neurotrauma ; 36(11): 1856-1868, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30582423

RESUMO

Diffuse axonal injury (DAI) is accompanied frequently by adverse sequelae and psychiatric disorders, such as anxiety, leading to a decreased quality of life, social isolation, and poor outcomes in patients. The mechanisms regulating psychiatric disorders post-DAI are not well elucidated, however. Previous studies showed that endoplasmic reticulum (ER) stress functions as a pivotal factor in neurodegeneration disease. In this study, we showed that DAI can trigger ER stress and unfolded protein response (UPR) activation in both the acute and chronic periods, leading to cell death and anxiety disorder. Treatment with 4-phenylbutyrate (4-PBA) is able to inhibit the UPR and cell apoptosis and relieve the anxiety disorder in our DAI model. Later (14 days post-DAI) 4-PBA treatment, however, can restore only the related gene expression of ER stress and UPR but not the psychiatric disorder. Therefore, the early (5 min after DAI) administration of 4-PBA might be a therapeutic approach for blocking the ER stress/UPR-induced cell death and anxiety disorder after DAI.


Assuntos
Transtornos de Ansiedade/etiologia , Lesão Axonal Difusa/complicações , Lesão Axonal Difusa/fisiopatologia , Estresse do Retículo Endoplasmático/fisiologia , Fenilbutiratos/farmacologia , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Fármacos Neuroprotetores/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/fisiologia
16.
Cell Mol Life Sci ; 75(22): 4207-4222, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29938386

RESUMO

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.


Assuntos
Axônios/fisiologia , Proteínas Ativadoras de GTPase/metabolismo , Receptor EphB1/metabolismo , Transdução de Sinais , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Células Cultivadas , Proteínas Ativadoras de GTPase/química , Proteínas Ativadoras de GTPase/fisiologia , Hipocampo/crescimento & desenvolvimento , Camundongos , Camundongos Knockout , Morfogênese , Domínios Proteicos
17.
Appl Environ Microbiol ; 83(22)2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28864657

RESUMO

Carpets have been implicated in prolonged and reoccurring outbreaks of human noroviruses (HuNoV), the leading cause of acute gastroenteritis worldwide. Viral recovery from environmental surfaces, such as carpet, remains undeveloped. Our aim was to determine survival of HuNoV surrogates on an understudied environmental surface, carpet. First, we measured the zeta potential and absorption capacity of wool and nylon carpet fibers, we then developed a minispin column elution (MSC) method, and lastly we characterized the survival of HuNoV surrogates, feline calicivirus (FCV) and murine norovirus (MNV), over 60 days under 30 and 70% relative humidity (RH) on two types of carpet and one glass surface. Carpet surface charge was negative between relevant pH values (i.e., pH 7 to 9). In addition, wool could absorb approximately two times more liquid than nylon. The percent recovery efficiency obtained by the MSC method ranged from 4.34 to 20.89% and from 30.71 to 54.14% for FCV and MNV on carpet fibers, respectively, after desiccation. Overall, elution buffer type did not significantly affect recovery. Infectious FCV or MNV survived between <1 and 15 or between 3 and 15 days, respectively. However, MNV survived longer under some conditions and at significantly (P < 0.05) higher titers compared to FCV. Albeit, surrogates followed similar survival trends, i.e., both survived longest on wool then nylon and glass, while 30% RH provided a more hospitable environment compared to 70% RH. Reverse transcription-quantitative PCR signals for both surrogates were detectable for the entire study, but FCV genomic copies experienced significantly higher reductions (<3.80 log10 copies) on all surfaces compared to MNV (<1.10 log10 copies).IMPORTANCE Human noroviruses (HuNoV) are the leading cause of acute gastroenteritis worldwide. Classical symptoms of illness include vomiting and diarrhea which could lead to severe dehydration and death. HuNoV are transmitted by the fecal-oral or vomitus-oral route via person-to-person contact, food, water, and/or environmental surfaces. Published laboratory-controlled studies have documented the environmental stability of HuNoV on hard surfaces, but there is limited laboratory-based evidence available about survival on soft surfaces, e.g., carpet and upholstered furniture. Several epidemiological reports have suggested soft surfaces may be HuNoV fomites illustrating the importance of conducting a survival study. The three objectives of our research were to demonstrate techniques to characterize soft surfaces, develop a viral elution method for carpet, and characterize the survival of HuNoV surrogates on carpet. These results can be used to improve microbial risk assessments, the development of much-needed soft surface disinfectant, and standardizing protocols for future soft surface studies.


Assuntos
Infecções por Caliciviridae/virologia , Calicivirus Felino/crescimento & desenvolvimento , Microbiologia Ambiental , Norovirus/crescimento & desenvolvimento , Animais , Calicivirus Felino/genética , Calicivirus Felino/isolamento & purificação , Gatos , Pisos e Cobertura de Pisos , Habitação , Humanos , Norovirus/genética , Norovirus/isolamento & purificação
18.
Front Mol Neurosci ; 10: 172, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28626389

RESUMO

The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of ß-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt. At the same time, the repression of NSCs proliferation caused by Porf-2 overexpression was counteracted by small molecule activators of Rac1 or Wnt. By using a rat optic nerve crush model, we observed that Porf-2 knockdown enhanced the recovery of visual function. In particular, optic nerve injury in rats led to increased Wnt family member 3a (Wnt3a) protein expression, which we found responsible for enhancing Porf-2 knockdown-induced NSCs proliferation. These findings suggest that Porf-2 exerts its inhibitory effect on NSCs proliferation via Rac1-Wnt/ß-catenin pathway. Porf-2 may therefore represent and interesting target for optic nerve injury recovery and therapy.

19.
Mol Cell Neurosci ; 80: 18-31, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28163190

RESUMO

The Rho family of small GTPases was considered as molecular switches in regulating multiple cellular events, including cytoskeleton reorganization. The Rho GTPase-activating proteins (RhoGAPs) are one of the major families of Rho GTPase regulators. RhoGAPs were initially considered negative mediators of Rho signaling pathways via their GAP domain. Recent studies have demonstrated that RhoGAPs also regulate numerous aspects of neuronal development and are related to various neurodegenerative diseases in GAP-dependent and GAP-independent manners. Moreover, RhoGAPs are regulated through various mechanisms, such as phosphorylation. To date, approximately 70 RhoGAPs have been identified; however, only a small portion has been thoroughly investigated. Thus, the characterization of important RhoGAPs in the central nervous system is crucial to understand their spatiotemporal role during different stages of neuronal development. In this review, we summarize the current knowledge of RhoGAPs in the brain with an emphasis on their molecular function, regulation mechanism and disease implications in the central nervous system.


Assuntos
Doenças do Sistema Nervoso Central/metabolismo , Sistema Nervoso Central , Proteínas Ativadoras de GTPase/metabolismo , Neurônios/fisiologia , Transdução de Sinais/fisiologia , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Sistema Nervoso Central/citologia , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Humanos
20.
Int J Biol Macromol ; 93(Pt A): 566-571, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27612645

RESUMO

Phellinus pini exopolysaccharide (PPE) is a mannan produced by P. pini when cultured in potato dextroseagar medium. Partial hydrolysis with acid, periodate oxidation and Smith degradation, methylation and 13C nuclear magnetic resonance (NMR) spectroscopy were used to elaborate its structure. Results indicated that PPE contained a backbone of (1→2)-linked Man, which was heavily substituted via (1→6)-glucosidic bonds with (1→3)-linked Man, and terminated mainly with Man, as well as a small amount of Gal and Glc. Immunological tests showed that PPE exhibited high macrophages-activating ability, thereby augmenting phagocytosis and enhancing the production of nitric oxide, tumour necrosis factor-α and reactive oxygen species. Therefor, PPE had potential applications in developing functional food or in serving as a natural immnunostimulant.


Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Basidiomycota/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Animais , Sequência de Carboidratos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Masculino , Camundongos
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