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1.
J Headache Pain ; 21(1): 47, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375638

RESUMO

BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. RESULTS: We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. CONCLUSION: In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.

2.
J Alzheimers Dis ; 75(1): 211-221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250297

RESUMO

BACKGROUND: Language dysfunction is a frequently reported symptom in Alzheimer's disease (AD). However, computer-assisted analysis of spontaneous speech in AD and mild cognitive impairment (MCI) is rarely used to date. OBJECTIVE: To characterize the language impairment in AD and amnestic MCI (aMCI) with computer-based automatic analysis via the "Automatic Speech Recognition (ASR) software for cognitive impairment V1.3". METHODS: A total of 64 subjects, including 20 AD patients, 20 aMCI patients, and 24 healthy controls were recruited. All subjects underwent neuropsychological tests, and spontaneous speech samples were recorded through the description of the "Cookie-Theft Picture" and then analyzed by the computerized software. Subsequently, we compared the speech parameters between the subjects and the controls. RESULTS: We identified seven spontaneous speech parameters (percentage of silence duration, average duration of phrasal segments, average duration of silence segments, number of speech segments, number of long pauses, ratio of hesitation/speech counts and ratio of short pause/speech counts) demonstrating significant differences between the three groups (p < 0.05). All seven speech parameters significantly correlated with cognitive performance, with average duration of silence segments demonstrating the best correlation to cognitive performance on stepwise multiple linear regression analysis. CONCLUSION: Computer-assisted automated analysis of speech/silence segments demonstrated the potential to reflect the intrinsic linguistic impairment associated with MCI and AD. It has a promising prospect in the early detection of AD and assessment of disease severity.

3.
Am J Obstet Gynecol ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32335053

RESUMO

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

4.
Phytother Res ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155298

RESUMO

Oxidative stress plays an important role in diabetic nephropathy (DN), which is a diabetic complication. Ampelopsin (AMP) is a natural flavonoid that has been found to possess antidiabetic and antioxidative activities. However, the effect of AMP on DN remains unclear. In this study, we aimed to evaluate the protective effect of AMP on glomerular mesangial cells (MCs) exposed to high glucose (HG). We found that AMP improved HG-caused cell viability reduction in MCs. AMP significantly suppressed the intracellular ROS production and expression levels of ROS producing enzymes NADPH oxidase 2 (NOX2) and NOX4. Increased of NOX activity in HG-stimulated MCs was suppressed by AMP. Pretreatment with AMP inhibited extracellular matrix (ECM) accumulation in HG-stimulated MCs with decreased expression levels of fibronectin (FN) and collagen type IV (Col IV). Furthermore, AMP elevated the expression levels of nuclear Nrf2 and heme oxygenase-1 (HO-1), as well as increased the mRNA levels of Nrf2-driven genes NAD(P)H dehydrogenase quinone-1 (NQO-1) and HO-1 in HG-treated MCs. Knockdown of Nrf2 reversed the protective effects of AMP against HG-induced oxidative stress and EMC accumulation in MCs. In conclusion, these findings indicated that AMP protected MCs from HG-induced oxidative damage and ECM accumulation, which might be mediated by Nrf2/HO-1 pathway.

5.
Reprod Sci ; 27(2): 704-712, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32046440

RESUMO

Results of previous epidemiology studies on BPA exposure and endometriosis (EMs) risk were inconsistent, and were limited by inappropriate control selection, incorrect BPA detection method, and the generalization of different subtypes of EMs. Upregulated matrix metalloproteinase (MMP) 2 and MMP9 are involved in the development of EMs. We conducted a case-control study among 120 EMs patients and 100 healthy women to evaluate the relationships between BPA exposure and MMP2, MMP9 expressions, and the risk of EMs subtypes. Besides, we used human endometrial stromal cell lines (HESCs) to investigate the underlying mechanisms. Creatinine-adjusted urinary BPA concentrations were positively correlated with serum MMP2, MMP9 levels, and the risk of peritoneal EMs (third vs lowest quartile: OR 4.92, 95% CI 1.47, 16.50; fourth versus lowest quartile: OR 3.70, 95% CI 1.07, 12.74, Ptrend = 0.030). The risk of peritoneal EMs increased approximately tenfold when creatinine-adjusted urinary BPA concentration was 2 µg/g. In vitro study found that BPA exposure increased MMP2, MMP9 expressions in a dose-dependent manner. The effects of BPA on HESCs could be blocked by G protein-coupled estrogen receptor (GPER) inhibitor or mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibitor. This study provides evidence that BPA exposure promotes peritoneal EMs, and raises a concern about the potential toxicity of BPA on the female reproductive system.

6.
J Cancer Res Clin Oncol ; 146(3): 739-748, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31832762

RESUMO

BACKGROUND: It is highly controversial that how to deal with the lateral lymph-node metastasis in patients with rectal cancer. Although lateral lymph node can be detected by preoperative MRI, the metastasis status cannot be accurately determined following standard total mesorectal excision (TME) in low-risk patients. This study was to assess the correlation between preoperative MRI detected lateral lymph-node (LLN) features and prognosis in patients with non-preradiated low recurrence risk rectal cancers. MATERIALS AND METHODS: This retrospective study included 593 low-risk rectal cancers underwent TME without neoadjuvant chemo-radiotherapy from January 2013 to December 2015. The features of the largest LLN were retrospectively reviewed on preoperative MRI. The relationship of MR-LLN features with overall survival, metastasis-free survival, and local relapse-free survival was analyzed. RESULTS: A total of 593 patients including 415 cases of pN0, 86 cases of pN1, and 92 cases of pN2 were enrolled in this study. In pN0 patients, at least one visible LLN was detected in 104 patients on primary MRI. The MR-T staging, postoperative therapy status, the presence of MR-LLN, and short axis (SA) of MR-LLN were significantly correlated with the recurrence in pN0 patients (all p < 0.05). The OS and MFS were significantly lower in patients with MR-LLN SA ≥ 8 mm than SA < 8 mm (p < 0.01, HR = 4.35, 95% CI = 1.48-12.77). The OS and MFS of patients with pN0-LLN(+) and SA ≥ 8 mm were similar to pN2-LLN(-) patients. The location of MR-LLN showed no significant impact on prognosis. CONCLUSION: For low-risk rectal cancers without neoadjuvant chemo-radiotherapy, the presence of MR-LLN is associated with poor prognosis. The pN0-LLN(+) SA ≥ 8 mm patients might be concerned as pN2 patients and receive more intensive neoadjuvant or adjuvant treatment.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Neoplasias Retais/mortalidade , Estudos Retrospectivos
7.
J Nurs Manag ; 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31811782

RESUMO

AIMS: To review the studies on nursing research capacity and the managerial approaches that have been taken to promote nursing research capacity building in China. BACKGROUND: In the nursing profession, research has become increasingly important worldwide. Over the last two decades, continuous efforts have been devoted to improving nursing research capacity in China. However, the results of these efforts were rarely evaluated in a national scale. EVALUATION: A systematic literature review was conducted in accordance with the PRISMA checklist and guidelines. The literature was sourced from PubMed, CINAHL and two Chinese databases. In total, 19 articles were selected and their results were integrated, compared and analysed. KEY ISSUES: The development of nursing research has become a recent phenomenon in China. Chinese nurses' perceptions regarding research were mostly positive. However, their participation in research activity has traditionally been minimal. The factors associated with nursing research capacity in China were nurses' personal characteristics and organisational contexts. Several effective strategies (e.g. on-the-job research education) have been used to promote nursing research capacity. CONCLUSION: Currently, nursing research capacity in China is low despite hospital-promoting efforts. Systematic approaches need to be implemented to increase nursing research capacity in China in the near future. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing administrators need to seek innovative strategies to resolve issues (e.g. lack of research time and limited nursing research resources). They also need to strengthen their leadership skills in order to achieve the above objectives.

8.
Int J Mol Sci ; 20(19)2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31590397

RESUMO

(1) Aims: The present study aimed to observe the effects of Ginsenoside Rb1 on high glucose-induced endothelial damage in rat retinal capillary endothelial cells (RCECs) and to investigate the underlying mechanism. (2) Methods: Cultured RCECs were treated with normal glucose (5.5 mM), high glucose (30 mM glucose), or high glucose plus Rb1 (20 µM). Cell viability, lactate dehydrogenase (LDH) levels, the mitochondrial DNA copy number, and the intracellular ROS content were measured to evaluate the cytotoxicity. Superoxide dismutase (SOD), catalase (CAT), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), poly(ADP-ribose) polymerase (PARP), and sirtuin (SIRT) activity was studied in cell extracts. Nicotinamide adenine dinucleotide (NAD+)/NADH, NADPH/NADP+, and glutathione (GSH)/GSSG levels were measured to evaluate the redox state. The expression of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), SIRT1, and SIRT3 was also evaluated after Rb1 treatment. (3) Results: Treatment with Rb1 significantly increased the cell viability and mtDNA copy number, and inhibited ROS generation. Rb1 treatment increased the activity of SOD and CAT and reduced the activity of NOX and PARP. Moreover, Rb1 enhanced both SIRT activity and SIRT1/SIRT3 expression. Additionally, Rb1 was able to re-establish the cellular redox balance in RCECs. However, Rb1 showed no effect on NMNAT1 expression in RCECs exposed to high glucose. (4) Conclusion: Under high glucose conditions, decreases in the reducing power may be linked to DNA oxidative damage and apoptosis via activation of the NMNAT-NAD-PARP-SIRT axis. Rb1 provides an advantage during high glucose-induced cell damage by targeting the NAD-PARP-SIRT signaling pathway and modulating the redox state in RCECs.


Assuntos
Antioxidantes/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Estresse Oxidativo , Vasos Retinianos/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Ginsenosídeos/farmacologia , Glucose/toxicidade , Masculino , NAD/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Sprague-Dawley , Vasos Retinianos/citologia , Vasos Retinianos/metabolismo , Transdução de Sinais , Sirtuínas/metabolismo
9.
J Nurs Manag ; 27(8): 1648-1654, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31444838

RESUMO

AIM: To develop and test the psychometric characteristics of the Inpatients' Involvement in Medication Safety Scale. BACKGROUND: Medication safety is the third biggest challenge threatening patient safety. Patient involvement in medication safety management is essential, and however, few tools have been developed to assess the related process. METHODS: The scale was formulated through literature review, semi-structured interviews and Delphi expert consultation. A group of 461 inpatients from a tertiary hospital were selected to examine the reliability and validity of the scale. RESULTS: The scale consisted of three dimensions and 23 items. Cronbach's α coefficient was 0.916 for the total scale and was 0.777-0.858 for three subscales; the test-retest reliability was 0.742 for the total scale. The content validity was 0.957, and the item content validity ranged from 0.833 to 1.000. The cumulative variance contribution of three selected factors was 51.19%. CONCLUSIONS: The Inpatients' Involvement in Medication Safety Scale has good reliability and validity and can be used to evaluate inpatients' involvement in medication safety. IMPLICATIONS FOR NURSING MANAGEMENT: The scale provides theoretical reference for clinical nursing safety management, as well as helps nurses to provide targeted medication care for patients and their families.

10.
ACS Appl Mater Interfaces ; 11(30): 26928-26937, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31282638

RESUMO

Side-chain polymers have the potential to be excellent dopant-free hole-transporting materials (HTMs) for perovskite solar cells (PSCs) because of their unique characteristics, such as tunable energy levels, high charge mobility, good solubility, and excellent film-forming ability. However, there has been less research focusing on side-chain polymers for PSCs. Here, two side-chain polystyrenes with triphenylamine substituents on carbazole moieties were designed and characterized. The properties of the side-chain polymers were tuned finely, including the photophysical and electrochemical properties and charge mobilities, by changing the positions of triphenylamine substituents on carbazole. Owing to the higher mobility and charge extraction ability, the polymer P2 with the triphenylamine substituent on the 3,6-positions of the carbazole unit showed higher performance with power conversion efficiency (PCE) of 18.45%, which was much higher than the PCE (16.78%) of P1 with 2,7-positions substituted. These results clearly demonstrated that side-chain polymers can act as promising HTMs for PSC applications and the performance of side-chain polymers could be optimized by carefully tuning the structure of the monomer, which provides a new strategy to design new kinds of side-chain polymers and obtain high-performance dopant-free HTMs.

11.
Mol Med Rep ; 20(2): 1451-1458, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173227

RESUMO

Preeclampsia (PE) is a complication of pregnancy, and a leading cause of maternal mortality and morbidity worldwide. Recently, the dysregulation of long non­coding RNAs (lncRNAs) has been reported to contribute to the pathogenesis and progression of PE. This study aimed to examine the alterations in the lncRNA family with sequence similarity 99 member A (FAM99A) in PE and its effects on trophoblasts. The results of reverse transcription­quantitative PCR indicated that the expression levels of FAM99A were downregulated in placental tissues from women with severe PE compared with in those from controls. A Transwell invasion assay and wound healing assay revealed that overexpression of FAM99A promoted invasion and migration of HTR­8/SVneo cells; conversely, knockdown of FAM99A suppressed the invasive and migratory abilities of HTR­8/SVneo cells. Flow cytometry demonstrated that FAM99A overexpression induced a decrease in the apoptotic rate of cells, whereas knockdown of FAM99A increased the apoptotic rate of HTR­8/SVneo cells. Western blot analysis revealed that overexpression of FAM99A decreased the protein expression levels of cleaved caspase­3, cleaved caspase­9 and Bax, and increased Bcl­2 protein expression, whereas knockdown of FAM99A had the opposite effects on these protein levels. Overexpression of FAM99A also decreased caspase­3 activity in HTR­8/SVneo cells; however, knockdown of FAM99A increased caspase­3 activity. In addition, overexpression of FAM99A enhanced Wnt/ß­catenin signaling activity, whereas FAM99A knockdown exerted an inhibitory effect on the Wnt/ß­catenin signaling activity in HTR­8/SVneo cells. In conclusion, these results indicated that FAM99A may serve a role in modulating the functions of trophoblasts, partially via targeting Wnt/ß­catenin signaling.


Assuntos
Pré-Eclâmpsia/genética , RNA Longo não Codificante/genética , Trofoblastos/metabolismo , Via de Sinalização Wnt/genética , Adulto , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/patologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
12.
Nat Microbiol ; 4(5): 766-773, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30833732

RESUMO

The human microbiota provides tonic signals that calibrate the host immune response1,2, but their identity is unknown. Bacterial peptidoglycan (PGN) subunits are likely candidates since they are well-known immunity-enhancing adjuvants, released by most bacteria during growth, and have been found in the blood of healthy people3-7. We developed a monoclonal antibody (mAb), 2E7, that targets muramyl-L-alanyl-D-isoglutamine (MDP), a conserved and minimal immunostimulatory structure of PGN. Using 2E7-based assays, we detected PGN ubiquitously in human blood at a broad range of concentrations that is relatively stable in each individual. We also detected PGN in the serum of several warm-blooded animals. However, PGN is barely detectable in the serum of germ-free mice, indicating that its origin is the host microbiota. Neutralization of circulating PGN via intraperitoneal administration of 2E7 suppressed the development of autoimmune arthritis and experimental autoimmune encephalomyelitis in mice. Arthritic NOD2-/- mice lacking the MDP sensor did not respond to 2E7, indicating that 2E7 dampens inflammation by blocking nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-mediated pathways. We propose that circulating PGN acts as a natural immune potentiator that tunes the host immune response; altering its level is a promising therapeutic strategy for immune-mediated diseases.


Assuntos
Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Artrite/tratamento farmacológico , Autoimunidade/efeitos dos fármacos , Bactérias/imunologia , Encefalomielite/tratamento farmacológico , Microbiota , Peptidoglicano/imunologia , Animais , Artrite/genética , Artrite/imunologia , Encefalomielite/genética , Encefalomielite/imunologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/imunologia , Peptidoglicano/sangue
13.
Neuroimage Clin ; 22: 101691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30708349

RESUMO

BACKGROUND: Computerized multi-model training has been widely studied for its effect on delaying cognitive decline. In this study, we designed the first Chinese-version computer-based multi-model cognitive training for mild cognitive impairment (MCI) patients. Neuropsychological effects and neural activity changes assessed by functional MRI were both evaluated. METHOD: MCI patients in the training group were asked to take training 3-4 times per week for 6 months. Neuropsychological and resting-state fMRI assessment were performed at baseline and at 6 months. Patients in both groups were continuously followed up for another 12 months and assessed by neuropsychological tests again. RESULTS: 78 patients in the training group and 63 patients in the control group accomplished 6-month follow-up. Training group improved 0.23 standard deviation (SD) of mini-mental state examination, while control group had 0.5 SD decline. Addenbrooke's cognitive examination-revised scores in attention (p = 0.002) and memory (p = 0.006), as well as stroop color-word test interference index (p = 0.038) and complex figure test-copy score (p = 0.035) were also in favor of the training effect. Difference between the changes of two groups after training was not statistically significant. The fMRI showed increased regional activity at bilateral temporal poles, insular cortices and hippocampus. However, difference between the changes of two groups after another 12 months was not statistically significant. CONCLUSIONS: Multi-model cognitive training help MCI patients to gained cognition benefit, especially in memory, attention and executive function. Functional neuroimaging provided consistent neural activation evidence. Nevertheless, after one-year follow up after last training, training effects were not significant. The study provided new evidence of beneficial effect of multi-model cognitive training.


Assuntos
Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/reabilitação , Remediação Cognitiva/métodos , Terapia Assistida por Computador/métodos , Idoso , Córtex Cerebral/diagnóstico por imagem , China , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
14.
Neurol Res ; 41(6): 536-543, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30810516

RESUMO

OBJECTIVE: Exposure to female estrous, a natural rewarding experience, alleviates anxiety and depression, and the contribution of this behavior to stroke outcome is unknown. The aim of this study was to evaluate whether exposure to female estrous is beneficial to recovery following transient ischemic stroke in male mice. METHODS: Cerebral ischemia was induced in male ICR mice with thread occlusion of the middle cerebral artery (MCAO) for 30 min followed by reperfusion. MCAO mice were randomly divided into MCAO group and Estrous Female Exposure (EFE) group. The mice in the EFE group were subjected to estrous female mouse interaction from day 1 until the end of the experiment. Mortality was recorded during the investigation. Behavioral functions were assessed by a beam-walking test and corner test from day 1 to day 10 after MCAO. Serum testosterone levels were analyzed with ELISA, and the expression levels of growth-associated protein-43 (GAP-43) and synaptophysin in the cortex of the ischemic hemisphere were determined by western blot on day 7 after MCAO. RESULTS: Exposure to female estrous reduced the mortality induced by cerebral ischemic lesions. The beam-walking test demonstrated that exposure to female estrous significantly improved motor function recovery. The serum testosterone levels and ischemic cortex GAP-43 expression were significantly higher in MCAO male mice exposed to female estrous. CONCLUSION: Exposure to female estrous reduces mortality and improves functional recovery in MCAO male mice. The study provides the first evidence to support the importance of female interaction to male stroke rehabilitation. ABBREVIATIONS: GAP-43: growth-associated protein-43; SYP: Synaptophysin; MCAO: middle cerebral artery occlusion; OVXs: ovariectomies; CCA: common carotid artery; ECA: external carotid artery; EFE: estrous female exposure; TTC: 2,3,5-triphenyltetrazolium chloride; PAGE: polyacrylamide gel electrophoresis; PVDF: polyvinylidene difluoride; ANOVA: analysis of variance; LSD: least significant difference.


Assuntos
Isquemia Encefálica/patologia , Infarto da Artéria Cerebral Média/patologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/patologia , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Artéria Cerebral Média/patologia , Reabilitação do Acidente Vascular Cerebral/métodos , Sinaptofisina/metabolismo
16.
Curr Cancer Drug Targets ; 19(1): 50-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30289077

RESUMO

BACKGROUND: The notion that proteasome inhibitor bortezomib (BTZ) induced intracellular oxidative stress resulting in peripheral neuropathy has been generally accepted. The association of mitochondrial dysfunction, cell apoptosis, and endoplasmic reticulum (ER) stress with intracellular oxidative stress is ambiguous and still needs to be investigated. The activation of activating transcription factor 3 (ATF3) is a stress-hub gene which was upregulated in dorsal root ganglion (DRG) neurons after different kinds of peripheral nerve injuries. OBJECTIVE: To investigate a mechanism underlying the action of BTZ-induced intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress via activation of ATF3. METHODS: Primary cultured DRG neurons with BTZ induced neurotoxicity and DRG from BTZ induced painful peripheral neuropathic rats were used to approach these questions. RESULTS: BTZ administration caused the upregulation of ATF3 paralleled with intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons both in vitro and in vivo. Blocking ATF3 signaling by small interfering RNA (siRNA) gene silencing technology resulted in decreased intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons after BTZ treatment. CONCLUSION: This study exhibited important mechanistic insight into how BTZ induces neurotoxicity through the activation of ATF3 resulting in intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress and provided a novel potential therapeutic target by blocking ATF3 signaling.

17.
Front Immunol ; 9: 2491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30443251

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs). They are ~22 nucleotides long and control both physiological and pathological processes. Altered expression of miRNAs is often associated with human diseases. Thus, miRNAs have become important therapeutic targets, and some clinical trials investigating the effect of miRNA-based therapeutics in different types of diseases have already been conducted. The tumor microenvironment (TME) comprises cells such as infiltrated immune cells, cancer-associated endothelial cells (CAEs) and cancer-associated fibroblasts (CAFs), and all the components participate in the complicated crosstalk with tumor cells to affect tumor progression. Altered miRNAs expression in both these stromal and tumor cells could drive tumorigenesis. Thus, in this review, we discuss how aberrantly expressed miRNAs influence tumor progression; summarize the crosstalk between infiltrated immune cells, CAEs, CAFs, and tumor cells through miRNAs, and clarify the important roles of miRNAs in the tumor microenvironment, which may facilitate the clinical application of miRNA-based therapies.


Assuntos
Fibroblastos Associados a Câncer/imunologia , Células Endoteliais/imunologia , Linfócitos do Interstício Tumoral/imunologia , MicroRNAs/genética , Neoplasias/genética , Animais , Carcinogênese , Regulação Neoplásica da Expressão Gênica , Humanos , Tolerância Imunológica , Imunidade Celular , Neoplasias/terapia , Microambiente Tumoral/genética
18.
Cell Physiol Biochem ; 51(1): 1-10, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30439711

RESUMO

BACKGROUND/AIMS: Lung cancer is the leading cause of cancer-related deaths worldwide. The outcome of patients with non-small cell lung cancer remains poor; the 5-year survival rate for stage IV non-small cell lung cancer is only 1.0%. KIF15 is a tetrameric kinesin spindle motor that has been investigated for its regulation of mitosis. While the roles of kinesin motor proteins in the regulation of mitosis and their potentials as therapeutic targets in pancreatic cancer have been described previously, the role of KIF15 in lung cancer development remains unknown. METHODS: Paired lung carcinoma specimens and matched adjacent normal tissues were used for protein analysis. Clinical data were obtained from medical records. We first examined KIF15 messenger RNA expression in The Cancer Genome Atlas database, and then determined KIF15 protein levels using immunohistochemistry and western blotting. Differences between the groups were analyzed using repeated measures analysis of variance. Overall survival was analyzed using the Kaplan-Meier method. Cell-cycle and proliferation assays were conducted using A549, NCI-H1299, and NCI-H226 cells. RESULTS: KIF15 was significantly upregulated at both the messenger RNA and protein levels in human lung tumor tissues. In patients with lung adenocarcinoma, KIF15 expression was positively associated with disease stages; high KIF15 expression predicted a poor prognosis. KIF15 knockdown using short hairpin RNA in two human lung adenocarcinoma cell lines induced G1/S phase cell cycle arrest and inhibited cell growth, but there was no effect in human lung squamous cell carcinoma. CONCLUSION: Our findings show that KIF15 is involved in lung cancer carcinogenesis. KIF15 could therefore serve as a specific prognostic marker for patients with lung adenocarcinoma.


Assuntos
Adenocarcinoma/patologia , Cinesina/metabolismo , Neoplasias Pulmonares/patologia , Células A549 , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Estimativa de Kaplan-Meier , Cinesina/antagonistas & inibidores , Cinesina/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo
19.
Sensors (Basel) ; 18(11)2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30400255

RESUMO

New amphiphilic star or multi-arm block copolymers with different structures were synthesized for enabling the use of hydrophobic oxygen probe of platinum (II)-tetrakis (pentafluorophenyl) porphyrin (PtTFPP) for bioanalysis. The amphiphilic star polymers were prepared through the Atom Transfer Radical Polymerization (ATRP) method by using hydrophilic 4-arm polyethylene glycol (4-arm-PEG) as an initiator. Among the five block copolymers, P1 series (P1a, P1b, and P1c) and P3 possess fluorine-containing moieties to improve the oxygen sensitivity with its excellent capacity to dissolve and carry oxygen. A polymer P2 without fluorine units was also synthesized for comparison. The structure-property relationship was investigated. Under nitrogen atmosphere, high quantum efficiency of PtTFPP in fluorine-containing micelles could reach to 22% and long lifetime could reach to 76 µs. One kind of representative PtTFPP-containing micelles was used to detect the respiration of Escherichia coli (E. coli) JM109 and macrophage cell J774A.1 by a high throughput plate reader. In vivo hypoxic imaging of tumor-bearing mice was also achieved successfully. This study demonstrated that using well-designed fluoropolymers to load PtTFPP could achieve high oxygen sensing properties, and long lifetime, showing the great capability for further in vivo sensing and imaging.


Assuntos
Flúor/química , Interações Hidrofóbicas e Hidrofílicas , Hipóxia/diagnóstico , Oxigênio/metabolismo , Platina/química , Porfirinas/química , Teoria Quântica , Tensoativos/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Respiração Celular , Sobrevivência Celular , Difusão Dinâmica da Luz , Escherichia coli/citologia , Humanos , Imageamento Tridimensional , Macrófagos/citologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Polímeros/síntese química , Polímeros/química , Espectroscopia de Prótons por Ressonância Magnética
20.
Dalton Trans ; 47(38): 13689-13695, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30209484

RESUMO

A series of novel boat-shaped host-guest complexes were designed and synthesized by the combination of a new calixarene fragment-based tetraphosphine ligand L with group 11 metal salts Cu(MeCN)4ClO4 and AgNO3 in a self-assembly process, and by the following anion exchange reactions of complex 1 with sodium p-toluenesulfonate, AcONa, PhCO2Na and sodium 9-anthrylcarboxylate. The host with a novel boat-shaped cavity is capable of self-adaptive encapsulation of various anions of different sizes through M(i)-O coordinations and CHπ interactions between the host and guest anion. The DFT calculations confirmed that the CHπ interaction played a vital role in the self-adaptive phenomenon in complexes 4-6.

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