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1.
J Biomed Mater Res A ; 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32363788

RESUMO

After bone tumor resection, the large bony deficits are commonly reconstructed with Ti based metallic endoprosthesis which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant-relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that, in the bacterial infection and Warburg effect of osteosarcoma induced acidic condition, naringin and Zn2+ can be released easily from the functional Ti substrate. The anti-osteosarcoma and antibacterial assay showed the delivered naringin and Zn2+ can induce remarkable increase of oxidative stress in bacteria (Escherichia coli and Staphylococcus aureus) and osteosarcoma (Saos-2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, increase of ROS induces osteosarcoma cell apoptosis by activating ROS/ERK signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase (ALP) activity, collagen secretion, extracellular matrix (ECM) mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti-based implants for the reconstruction of large bony after osteosarcoma resection. This article is protected by copyright. All rights reserved.

3.
J Diabetes Res ; 2020: 3251275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32258164

RESUMO

Background: Emerging studies have explored the association between the famine exposure during early life and the risk of the metabolic syndrome, and the results remain controversial. This meta-analysis was performed to summarize the famine effects on the prevalence of metabolic syndrome (MetS) in adulthood. Materials and Methods. We searched the PubMed, Web of Science, Embase, ScienceDirect, and Chinese National Knowledge Infrastructure for relevant studies up to December 2019. Pooled odd ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effect exposure to famine on MetS using a random-effects model, and the I 2 was used to evaluate the heterogeneity. Results: The analyses included 39 studies from 10 articles with a total of 81504 participants. Fourteen studies from 10 articles for fetal famine exposure, 20 studies from 7 articles for childhood famine exposure, and 5 studies from 3 articles for adolescence/adult famine exposure were included in this meta-analysis. Compared with a nonexposed group, famine exposure significantly increased the risk of MetS for early life famine exposure (OR = 1.27, 95% CI: 1.18-1.38), fetal famine exposure (OR = 1.27, 95% CI: 1.14-1.43), and childhood famine exposure (OR = 1.29, 95% CI: 1.16-1.44). Subgroup analyses showed that the result was consistent regardless of the study designs, definitions of MetS, and causes of famine, with or without adjustment for age, smoking, drinking, and physical activity. Conclusions: This meta-analysis suggests that exposure to famine during early life may increase the risk of MetS in adulthood.

4.
PLoS One ; 15(4): e0231201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294123

RESUMO

BACKGROUND: Emerging studies have found inconsistent results on the potential relationship between cigarette smoking and dysmenorrhea. Therefore, the aim of this study was to quantitatively synthesize the previous findings on the preceding relationship using meta-analysis. METHODS: Previous studies on the association between cigarette smoking and dysmenorrhea, published not later than November 2019, were systematically searched, using MeSH heading and/or relevant terms, in the electronic databases of PubMed, Medline, Web of Science and EMBASE. The I2 statistic was used to assess heterogeneity, whose source was explored using subgroup analysis. A pooled effect size was obtained using random effects model, and sensitivity analysis was performed to assess the consistency of the pooled effect size. RESULTS: After a rigorous screening process, 24 studies involving 27,091 participants were included in this meta-analysis. The results indicated that smokers were 1.45 times more likely to develop dysmenorrhea than non-smokers (odds ratio (OR) = 1.45, 95% confidence interval (CI): 1.30-1.61). In addition, individuals classified as currently smoking were 1.50 times more likely to develop dysmenorrhea than those who were classified as never smoking (OR = 1.50, 95% CI: 1.33-1.70), whereas being a former smoker was 1.31 times more likely to develop dysmenorrhea than being a never smoker (OR = 1.31, 95% CI: 1.18-1.46). Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect. CONCLUSION: The evidence from this meta-analysis indicated a significant association between cigarette smoking (both current and former smoking) and dysmenorrhea. The adverse effects of smoking provide further support for prevention of dysmenorrhea and emphasize the need to target women.

6.
Am J Physiol Regul Integr Comp Physiol ; 318(4): R772-R780, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101460

RESUMO

Femoral artery occlusion in rats has been used to study human peripheral artery disease (PAD). Using this animal model, a recent study suggests that increases in levels of tumor necrosis factor-α (TNF-α) and its receptor lead to exaggerated responses of sympathetic nervous activity and arterial blood pressure as metabolically sensitive muscle afferents are activated. Note that voltage-dependent Na+ subtype NaV1.8 channels (NaV1.8) are predominately present in chemically sensitive thin fiber sensory nerves. The purpose of this study was to examine the role played by TNF-α in regulating activity of NaV1.8 currents in muscle dorsal root ganglion (DRG) neurons of rats with PAD induced by femoral artery occlusion. DRG neurons from control and occluded limbs of rats were labeled by injecting the fluorescent tracer DiI into the hindlimb muscles 5 days before the experiments. A voltage patch-clamp mode was used to examine TTX-resistant (TTX-R) NaV currents. Results were as follows: 72 h of femoral artery occlusion increased peak amplitude of TTX-R [1,922 ± 139 pA in occlusion (n = 11 DRG neurons) vs. 1,178 ± 39 pA in control (n = 10), means ± SE; P < 0.001 between the 2 groups] and NaV1.8 currents [1,461 ± 116 pA in occlusion (n = 11) and 766 ± 48 pA in control (n = 10); P < 0.001 between groups] in muscle DRG neurons. TNF-α exposure amplified TTX-R and NaV1.8 currents in DRG neurons of occluded muscles in a dose-dependent manner. Notably, the amplification of TTX-R and NaV1.8 currents induced by TNF-α was attenuated in DRG neurons with preincubation with respective inhibitors of the intracellular signaling pathways p38-MAPK, JNK, and ERK. In conclusion, our data suggest that NaV1.8 is engaged in the role of TNF-α in amplifying muscle afferent inputs as the hindlimb muscles are ischemic; p38-MAPK, JNK, and ERK pathways are likely necessary to mediate the effects of TNF-α.

7.
J Physiol ; 598(8): 1491-1503, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32052864

RESUMO

KEY POINTS: During exercise, the blood pressure (BP) response is exaggerated in peripheral artery disease (PAD). We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats. With HT (increase in basal muscle temperature of ∼1.5°C for 30 min, twice daily for three continuous days), the amplified BP response to muscle contraction is alleviated in PAD. We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X3 and the increase in P2X currents in the muscle afferent neurons of PAD rats. Previous heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is probably a part of the mechanism mediating this improvement. ABSTRACT: The current study was performed to examine if heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD). We further determined if the temperature-sensitive P2X receptor is involved in the effects of HT. The pressor response to static muscle contraction and α,ß-methylene ATP (αß-me ATP, a P2X agonist) was examined. Western blot analysis was used to determine the protein levels of P2X3 in the dorsal root ganglion (DRG), and the whole cell patch clamp was used to examine the amplitude of P2X currents in the DRG neurons. The basal muscle temperature (Tm ) was lower in PAD rats than in control rats. Tm was increased by ∼1.5°C and this increase was maintained for 30 min. This HT protocol was performed tweice daily for three continuous days. A greater blood pressure (BP) response to contraction was observed in PAD rats. HT attenuated the amplification of the BP response in PAD rats. HT also attenuated the enhancement of the BP response induced by the arterial injection of αß-me ATP in PAD rats. In addition, HT attenuated the upregulation of the P2X3 and increased P2X currents in the DRG neurons of PAD rats. In conclusion, previous heat exposure plays an inhibitory role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction of the activity of the P2X receptor pathway is probably a part of mechanisms leading to the beneficial effects of HT.

8.
BMC Pediatr ; 20(1): 61, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039717

RESUMO

BACKGROUND: Plastic bronchitis (PB) frequently occurs as a serious postoperative complication of the Fontan procedure. The definitive causes of PB are unknown. CASE PRESENTATION: Herein, we report a pediatric case of PB secondary to adenoviral infection. A 4-year-old girl was admitted to the general pediatric ward for cough since 2 weeks and fever since 11 days. Consolidated lesions were noted in the right upper and both lower lung lobes. Extracorporeal membrane oxygenation was performed because the patient's respiratory failure remained unalleviated despite the use of a ventilator. Bronchial dendritic casts were extracted using flexible bronchoscopy, and the patient's breathing improved. Pathological examination of the dendritic cast confirmed the diagnosis of type I PB. The exfoliated cells of sputum and cells from bronchoalveolar lavage fluid were positive for adenoviral antigen. Human adenovirus 7 was detected by next-generation sequencing of the bronchoalveolar lavage fluid. The patient recovered and was discharged 39 days after admission without recurrence of cough or wheezing. CONCLUSIONS: PB due to human adenovirus 7 infection should be considered in children with persistent respiratory failure. Flexible bronchoscopy should be performed early to confirm diagnosis and to remove any airway obstruction.

9.
J Control Release ; 321: 641-653, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32097672

RESUMO

Macromolecular drugs, characterized by low stability and large molecular weight, still faced various difficulties by oral administration. And controlling drugs' release rate to reach the physiological concentration in the blood was recognized as one of the main challenges in this field but no studies are available so far. Thus, the objective of this study was to investigate the effect of insulin release rate on its in vitro and in vivo behavior when other obstacles (drug stability, mucus penetration and retention in gastrointestinal tract) was firstly overcome. Using n-butylcyanoacrylate (BCA) as the carrier, insulin-loaded Poly (n-butylcyanoacrylate) nanoparticles (Ins/PBCA NPs) were prepared by self-polymerization and the release rate of insulin was controlled by adjusting the mass ratio of Insulin/BCA. The NPs exhibited good stability in gastric fluid with controlled release in intestine and the release rate increased with the increase of Insulin/BCA mass ratio. All the Ins/PBCA NPs with different release rate showed excellent mucus penetration (>60%, 10 min) and strong gastrointestinal retention (~70%, 12 h). Especially, all the NPs showed promising hypoglycemic effect with the extent depending on drug release rate. Ins/BCA = 2/10 NPs exhibited fast hypoglycemic effect, while Ins/BCA = 2/15 NPs showed slow and outstanding performance. In conclusion, Ins/PBCA NPs could not only overcome the oral barriers of insulin delivery but also provide desired hypoglycemic effect by controlling insulin release rate.

10.
Int J Pharm ; 575: 119000, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31893544

RESUMO

Based on dry powder inhaler (DPI) inhalation process, powder properties have a key influence on fluidization and deagglomeration behavior during aerosol generation. The aim of this study was to explore the influence of drug content on DPI powder properties and further reveal the correlations between powder properties and pulmonary deposition efficiency. Using salbutamol sulfate as a model drug, Lactohale® 100 as carrier, carrier-based binary mixtures were prepared at drug content from 0.5 to 10% (w/w), characterized with powder rheometer, faraday cage and Next Generation Impactor. It was demonstrated that drug content had a remarkable influence on powder behavior, and good correlations between powder properties and fine particle fraction (FPF) were established in drug content range 0.5-7%. A negative correlation between basic flowability energy and FPF, reflected a good flowability is beneficial for powder fluidization. Further properties characterization, including aeration ratio, permeability, pre-shear stress and aerodynamic specific charge, suggested a strong interaction is beneficial for powder deagglomeration. It's the first time that interaction indicator and flowability indicator were extracted with principal component analysis (PCA). In conclusion, drug content has a significant influence on powder properties. DPI formulations with a stronger interaction and meanwhile a better flowability are desirable for enhanced pulmonary drug delivery.

11.
Epilepsy Behav ; 103(Pt A): 106858, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899164

RESUMO

In this study, we aimed to detect longitudinal alterations in local spontaneous brain activity and functional connectivity (FC) of the default mode network (DMN) in patients with temporal lobe epilepsy (TLE) over a two-year follow-up. We used amplitude of low-frequency fluctuation (ALFF) analysis and independent component analysis (ICA) to explore differences in local spontaneous brain activity and FC strength. In total, 33 participants (16 patients with TLE and 17 age- and gender-matched healthy controls (HCs)) were recruited in this study. All participants performed the Attention Network Test (ANT) for evaluation of the executive control function. Compared with healthy patients at baseline, patients with TLE at follow-up exhibited increased ALFF values in the left medial frontal gyrus, as well as reduced FC values in the left inferior parietal gyrus (IPG) within the DMN. Patients with TLE revealed executive dysfunction, but no progressive deterioration was observed during follow-up. This study revealed the abnormal distribution of ALFF values and Rs-FC changes over a two-year follow-up period in TLE, both of which demonstrated different reorganization trajectories and loss of efficiency.

12.
Life Sci ; 245: 117362, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31996295

RESUMO

The prominent feature of obstructive sleep apnea (OSA) is chronic intermittent hypoxia (CIH). Given the strong antioxidant ability of resveratrol against oxidative stress, we evaluated the potential protective effects of resveratrol on myocardial injury induced by CIH. Twenty-four rats were divided into normal control group, CIH group, CIH plus resveratrol treated (CIH + Res) group, and resveratrol treated control (Res) group. We proved that CIH impaired cardiac structure and function with an increase in oxidative stress, endoplasmic reticulum (ER) stress and NOD-like receptors (NLRP3) inflammasome induction in heart, which was attenuated after resveratrol administration. NLRP3 inflammasome blockade by resveratrol appeared to be mediated by activating AMP-activated Protein Kinase (AMPK), which could restrain mTOR/TTP/NLRP3 mRNA signalling. Furthermore, resveratrol attenuated CIH-induced oxidative stress through elevation antioxidant molecules expression via NF-E2-related factor-2 (Nrf2). Moreover, AMPK may play a role in Nrf2/HO-1 signalling by resveratrol. These results expand our understanding of the myocardial protective mechanism of resveratrol during CIH and suggest that resveratrol treatment may be useful to counteract OSA-associated cardiac injury.


Assuntos
Antioxidantes/uso terapêutico , Hipóxia/complicações , Inflamassomos/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Resveratrol/uso terapêutico , Animais , Antioxidantes/farmacologia , Western Blotting , Ecocardiografia , Imunofluorescência , Inflamassomos/metabolismo , Masculino , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol/farmacologia
13.
Drug Discov Today ; 25(1): 150-159, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31600580

RESUMO

The inhaled delivery of nanomedicines has attracted much attention in the treatment of lung diseases or systemic diseases. However, there is a lack of understanding about their fate upon lung delivery. Thus, the objective of this review is to summarize physicochemical properties affecting the fate of nanoparticles after deposition in the lung. First, physiological structure and characteristics of the lung are described. Thereafter, physicochemical properties that could influence the clearance and translocation of nanoparticles in the lung are discussed, including particle size, surface charge and surface hydrophilicity. It is believed that, with a better understanding of the fate of nanoparticles in the lung, it will broaden their application in inhalation for a better therapeutic effect in the future.

14.
Fish Shellfish Immunol ; 97: 344-350, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846776

RESUMO

To study the effect of dietary supplementation of Bacillus licheniformis FA6 on the growth, survival and intestinal health of grass carp, we assessed the antioxidant capacity, intestinal barrier, expression levels of immune genes, and the resistance to Aeromonas hydrophila AH-1 infection. Experimental setup comprised three groups (90 specimens each; average initial weight = 16.5 g): the control group was fed the basal diet without B. licheniformis, the low-dose (LD) group was supplemented with B. licheniformis at the concentration of 1 × 105 cfu/g, and the high-dose (HD) group with 1 × 106 cfu/g. After 56 days of growth trial, the challenge test with A. hydrophila AH-1 was conducted for 14 days. The results revealed that the grass carp in LD group and HD group had significantly (p < 0.05) improved percent weight gain (PWG) and specific growth rate (SGR) parameters. Additionally, the antioxidant status was improved, which included increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) levels in the serum, and upregulated mRNA levels of antioxidant enzymes MnSOD and catalase (CAT) in the intestine. Meanwhile, B. licheniformis FA6 supplementation groups exhibited a decreased mRNA expression of proinflammatory cytokines (such as IL-1ß and TNF-α) and increased the expression of anti-inflammatory cytokine IL-10. Histological (villi length was increased) and gene expression (qPCR: upregulated ZO-1, occludin, and claudin-c) analyses suggested improved functioning of the intestinal barrier. Post-challenge mortality rates in LD and HD groups were significantly lower (56.6% and 70% respectively) than in the control group (100%). Overall, these results indicated that dietary supplementation of B. licheniformis FA6 can improve growth, antioxidant capacity, intestinal barrier functions and disease resistance of grass carp.

15.
BMC Med Inform Decis Mak ; 19(Suppl 5): 234, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31801523

RESUMO

BACKGROUND: To robustly identify synergistic combinations of drugs, high-throughput screenings are desirable. It will be of great help to automatically identify the relations in the published papers with machine learning based tools. To support the chemical disease semantic relation extraction especially for chronic diseases, a chronic disease specific corpus for combination therapy discovery in Chinese (RCorp) is manually annotated. METHODS: In this study, we extracted abstracts from a Chinese medical literature server and followed the annotation framework of the BioCreative CDR corpus, with the guidelines modified to make the combination therapy related relations available. An annotation tool was incorporated to the standard annotation process. RESULTS: The resulting RCorp consists of 339 Chinese biomedical articles with 2367 annotated chemicals, 2113 diseases, 237 symptoms, 164 chemical-induce-disease relations, 163 chemical-induce-symptom relations, and 805 chemical-treat-disease relations. Each annotation includes both the mention text spans and normalized concept identifiers. The corpus gets an inter-annotator agreement score of 0.883 for chemical entities, 0.791 for disease entities which are measured by F score. And the F score for chemical-treat-disease relations gets 0.788 after unifying the entity mentions. CONCLUSIONS: We extracted and manually annotated a chronic disease specific corpus for combination therapy discovery in Chinese. The result analysis of the corpus proves its quality for the combination therapy related knowledge discovery task. Our annotated corpus would be a useful resource for the modelling of entity recognition and relation extraction tools. In the future, an evaluation based on the corpus will be held.

17.
Int J Neurosci ; : 1-11, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31851554

RESUMO

Objective: We aimed to explore functional connectivity (FC) and effective connectivity (EC) of the executive control networks (ECNs) and the default mode network (DMN) in patients with right-sided TLE (rTLE) by applying independent component analysis (ICA) and Granger causal analysis (GCA).Methods: Twenty-seven patients with rTLE and 20 healthy controls (HCs) matched for age, gender underwent resting-state functional magnetic resonance imaging and Attention Network Test (ANT).Results: The FC analysis showed compared to HCs, patients with rTLE demonstrated reduced FC strength in the right inferior parietal gyrus (IPG) and the right middle temporal gyrus (MTG). The left superior temporal gyrus (STG) displayed reduced FC values whereas the left thalamus revealed increased FC values in rTLE. ROI-wise GCA revealed that patients with rTLE displayed increased EC from the left thalamus to the left STG, and as well as enhanced EC from the right IPG to the right MTG compared to HCs. Voxel-wise GCA showed positive EC from the left thalamus to the left insula while the right middle occipital gyrus (MOG) exhibited increased EC to the right MTG in patients. The ANT results demonstrated executive dysfunction in patients compared to HCs. The increased FC in the left thalamus showed a negative association with ECF in patients.Conclusion: We speculated that recurrent seizures take effect on disruption among the brain networks, and self-modulation occurs simultaneously to compensate for cognitive decline. Our findings revealed new insights on the neuropathophysiological mechanisms of rTLE.

18.
Infect Agent Cancer ; 14: 29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673281

RESUMO

Microecology is an emerging discipline in recent years. The female reproductive tract is an important microecological region, and its microecological environment can directly affect women's cervical health. This meta-analysis aimed to analyze the effects of vaginal microecology on Human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). PubMed and Web of Science were systematically searched for eligible publications from January 2000 to December 2017. Articles were selected on the basis of specific inclusion and exclusion criteria. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) with a 95% confidence interval (95% CI) were calculated. Thirteen eligible studies were selected to evaluate the association of vaginal microecology with HPV infection and CIN. The factors related to HPV infection were bacterial vaginosis (BV) (OR 2.57, 95% CI 1.78-3.71, P<0.05), Candida albicans (VVC) (OR 0.63, 95% CI 0.49-0.82, P < 0.05), Chlamydia trachomatis (CT) (OR 3.16, 95% CI 2.55-3.90, P < 0.05), and Ureaplasma urealyticum (UU) (OR 1.35, 95% CI 1.20-1.51, P < 0.05). BV was also related to CIN (OR 1.56, 95% CI 1.21-2.00, P < 0.05). This meta-analysis of available literature suggested an intimate association of vaginal microecology and HPV infection with CIN. BV, CT and UU were associated to increased HPV infection, VVC was associated to decreased HPV infection, Lactobacillus is not associated to increased HPV infection, BV was associated to increased CIN development risk. Further large-scale studies are needed to confirm our findings.

19.
Epilepsy Behav ; 101(Pt A): 106573, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677580

RESUMO

Cognitive impairment is common in patients with temporal lobe epilepsy (TLE). Alertness is an important subfunction of cognition, but it is poorly understood in TLE. We hypothesized that disruptions to underlying brain networks may affect alertness in patients with TLE. Patients with unilateral TLE were grouped into low-alertness and high-alertness groups, and they were matched with healthy controls (HCs) (n = 20 each). Functional magnetic resonance imaging (fMRI) was used to construct functional brain networks, and graph theory was used to identify topological parameters of the networks. At the global level, patients with low alertness had networks with less small-worldness and less normalized clustering than HCs. At the nodal level, patients with low alertness exhibited decreased centrality of the bilateral parahippocampal gyrus compared with HCs and increased centrality of the right postcentral gyrus compared with patients with high alertness. This study reveals a decreased separation, tending toward randomization, of the functional network in patients with TLE with impaired alertness. Our results also suggest that the parahippocampal gyrus may contribute to impaired alertness and the right postcentral gyrus plays an important role in the modulation of alertness in patients with TLE.

20.
Int Immunopharmacol ; 77: 105973, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677992

RESUMO

Sepsis is a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection. Macrophage polarization is a key process involved in the pathogenesis of sepsis. Recent evidence has demonstrated that autophagy participates in the regulation of macrophage polarization in different phases of inflammation. Here, we investigated whether trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the macrophage M2 phenotype by enhancing autophagy to counteract excessive inflammation in a cecal ligation and puncture (CLP) mouse model. TSA stimulation increased the proportions of M2 marker (CD206, CD124 and CD23)-labeled RAW264.7 macrophages. Furthermore, with increasing TSA doses, autophagy was enhanced gradually. Interestingly, the autophagy activator rapamycin (Rap), also known as an mTOR inhibitor, unexpectedly decreased the proportions of M2 marker-labeled macrophages. However, TSA treatment reversed the Rap-induced decreases in CD206-labeled macrophages. Next, we stimulated different groups of RAW264.7 cells with the autophagy inhibitors MHY1485 or 3-methyladenine (3-MA). Inhibition of autophagy at any stage in the process suppressed TSA-induced macrophage M2 polarization, but the effect was not associated with mTOR activity. In vivo, TSA administration promoted peritoneal macrophage M2 polarization, increased LC3 II expression, attenuated sepsis-induced organ (lung, liver and kidney) injury, and altered systemic inflammatory cytokine secretion. However, 3-MA abolished the protective effects of TSA in CLP mice and decreased the number of M2 peritoneal macrophages. Therefore, TSA promotes the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improves the survival of mice with polymicrobial sepsis.

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