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OBJECTIVE: To observe the effect of point-toward-point insertion of elongated needle on post-stroke fatigue and explore its underlying mechanism. METHODS: Sixty-four patients with post-stroke fatigue were randomly divided into an observation group (32 cases, 2 cases dropped out) and a control group (32 cases, 2 cases dropped out). In addition to the conventional treatment of western medicine and rehabilitation exercises, Tongdu Tiaoshen (regulating the governor vessel and the spirit) therapy of acupuncture was used in the control group, and acupuncture was applied to Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Fengfu (GV 16) and bilateral Fengchi (GB 20) and the needles were retained for 30 min in one treatment. In the observation group, besides the interventions as the control group, point-toward-point insertion of elongated needle was adopted. The needle was inserted from Zhiyang (GV 9) toward Dazhui (GV 14), from Shendao (GV 11) toward Yaoyangguan (GV 3) and from Yaoqi (EX-B 9) toward Yaoyangguan (GV 3); and the needles were retained for 30 min in one treatment. In the two groups, the acupuncture was delivered once daily, 6 times a week, consecutively for 4 weeks. The scores of the fatigue severity scale (FSS), Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Fugl-Meyer assessment (FMA) were observed before and after treatment completion in the two groups. Using ELISA, the levels of serum interleukin (IL)-1ß, IL-6, IL-10, high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) were detected before and after treatment completion; and clinical effect was evaluated. RESULTS: The scores of FSS, PSQI, HAMA and HAMD, as well as the levels of serum IL-1ß, IL-6, hs-CRP and Hcy were reduced (P<0.05), and the scores of FMA and the levels of serum IL-10 were increased (P<0.05) after treatment in comparison with those before treatment in the two groups. Compared with the control group, in the observation group, the scores of FSS, PSQI, HAMA and HAMD, and the levels of serum IL-1ß, IL-6, hs-CRP and Hcy were reduced (P<0.05, P<0.01), and the score of FMA and the level of serum IL-10 were increased (P<0.05). The total clinical effective rate was 83.3% (25/30) in the observation group, which was higher than 73.3% (22/30) of the control group (P<0.05). CONCLUSION: The point-toward-point insertion of elongated needle alleviates fatigue, anxiety and depression, and ameliorates sleep and motor function in the patients with post-stroke fatigue. It may be related to the attenuation of inflammatory responses.
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Pontos de Acupuntura , Terapia por Acupuntura , Fadiga , Acidente Vascular Cerebral , Humanos , Terapia por Acupuntura/instrumentação , Feminino , Masculino , Pessoa de Meia-Idade , Fadiga/terapia , Fadiga/etiologia , Fadiga/fisiopatologia , Idoso , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Adulto , Interleucina-6/sangue , Resultado do Tratamento , Interleucina-10/sangueRESUMO
In traditional Chinese Medicine, Prunella vulgaris L. (PVL) is potentially effective in the treatment of some human malignancies including hepatocellular carcinoma (HCC). However, the detailed mechanism of action remains unclear. The purpose of this study was to decipher the constitutes of the bioactive ingredients of PVL, and its mechanism against HCC using network pharmacology and in vitro experiments. The bioactive components of PVL were obtained by Traditional Chinese Medicine System Pharmacology Database and Analysis platform database, and the targets of bioactive components of PVL was investigated by Swiss Target Prediction database. HCC related targets were obtained from GEO database, GeneCards database and DisGeNET database, and the gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted for annotating the biological function of gene targets. A protein-protein interaction network was constructed using STRING database. Molecular docking of key bioactive ingredients was performed using AutoDock Vina. Cell proliferation and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. The expression level of the target genes of PI3K/Akt pathway were detected by qPCR. In the present work, 11 bioactive components of PVL were screened out, which acted on 177 potential targets. In addition, 13,517 genes were strongly associated with HCC pathogenesis, of which 158 targets are overlapped with PVL's targets. KEGG results identified 39 signaling pathways closely associated with the 158 targets. Molecular docking showed that the main bioactive components of PVL, kaempferol, morin, quercetin, luteolin, and spinasterol, had good binding activity with the core proteins in cancer biology such as AKT1, EGFR, SRC, ESR1, and PPARG. In vitro assays showed that quercetin, one of the main components of PVL extracts effectively inhibited HCC cell proliferation, and promoted apoptosis, which may be associated with PI3K/AKT signaling pathway. In summary, PVL may regulate HCC progression by regulating core targets such as AKT1, EGFR, SRC, ESR1, and PPARG, and acting on PI3K-Akt signaling pathway.
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Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Prunella , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , PPAR gama , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Quercetina , Neoplasias Hepáticas/tratamento farmacológico , Receptores ErbB , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
BACKGROUND: This research aims to generate normative values of hyperopia reserve and refractive progression as effective tools to estimate the risk of myopia. METHODS: A 1-year follow-up study was conducted among Chinese children and adolescents aged 3-16 years selected from schools and kinder gardens using cluster sampling. All participants underwent examinations including visual acuity, axial length and cycloplegic autorefraction (1% cyclopentolate). Percentiles of spherical equivalent (SE) were calculated using Lambda-Mu-Sigma (LMS) method. Age-specific refractive progression and hyperopia reserve were determined by backward calculation. RESULTS: Of 3118 participants, 1702 (54.6%) were boys with a mean baseline age of 7.30 years. The 50th percentile of SE estimated by LMS decreased from 1.04 D at 3 years to -2.04 D at 16 years in boys, while from 1.29 D to -2.81 D in girls. The 1-year refractive progression of myopes (0.81 D) was greater than that of non-myopes (0.51 D). The normative value of hyperopia reserve was 2.64 (range: 2.40 D-2.88 D) at 3 years and -0.35 (range: -0.50 to -0.17) D at 16 years, with the maximum progression of 0.35 D at the age of 6 years. CONCLUSION: Age-specific normative values of hyperopia reserve and yearly myopic shift in children and adolescents aged 3-16 years were provided, helping identify and monitor myopia and giving prevention in advance.
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Tracheostomy and delayed extubation (DE) are two methods for managing patients' airways postoperatively after oral and maxillofacial free flap transplantation. We aimed to determine the safety of both the tracheostomy and DE by conducting a retrospective study in patients undergoing oral and maxillofacial free-flap transfer from September, 2017 to September, 2022. The primary outcome was incidence of postoperative complication. Secondary outcome was measured as factors leading to perioperative performance of airway management. Ninety-five of 148 patients received delayed extubation perioperatively. In comparison to the tracheostomy group, the DE group had fewer overall postoperative complications (p = 0.028). During the postoperative period, fewer patients from the DE group required a return to the operating room, in comparison to those from the tracheostomy group (p = 0.045). The duration of surgery (p = 0.006), time in ICU (p = 0.015), duration of artificial nutrition (p < 0.001), duration of hospitalization (p < 0.001) in the DE group were all significantly shorter when compared with the tracheostomy group. In conclusion, when used in appropriate cases of oral and maxillofacial free flap transplantation patients, delayed extubation can be a safe and effective alternative to tracheostomy.
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Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos , Extubação , Traqueostomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Introduction: The microbiota-gut-brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats. Methods: The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC). Results: The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and Lactobacillus intestinalis. Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids. Discussion: According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota-gut-brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.
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Background and objective: Alzheimer's disease (AD) is characterized by amyloid ß (Aß) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD. Methods: The APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral INH (45 mg/kg/d) for 14 days. The cognitive capability was assessed by the Morris Water Maze test. Amyloid plaques and Aß levels were determined by immunohistochemistry and ELISA assay. The dendritic spines were analyzed by DiOlistic labeling. Immunofluorescence staining was used to observe the microglia and astrocytes. Results: The Morris Water Maze test suggested that INH administration can effectively attenuate the reference memory deficit and improve the working memory of the APP/PS1 mice compared to the untreated mice (all p < 0.001). INH significantly decreased the Aß plaques in the hippocampus and cortex and reduced the levels of Aß1-40 and Aß1-42 in the brain homogenates, cerebrospinal fluid, and serum (all p < 0.001). INH also inhibited enzyme activities of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1, p < 0.05) and monoamine oxidase B (Mao-b, p < 0.01). INH significantly increased the protrusion density in the hippocampus (p < 0.01). Immunofluorescence staining revealed that INH significantly reduced the number of activated microglia and astrocytes around the Aß plaques (both p < 0.01). Conclusion: Isoniazid administration effectively improved cognitive performance, cleared Aß plaques, protected dendritic synapses, and reduced innate immune cells around the Aß plaques, suggesting that INH could be a potential drug for AD treatment.
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OBJECTIVE: to investigate the feasibility of gadoxetic acid (Gd-EOB-DTPA) enhanced MRI combined with T1 mapping in quantitative hepatic function assessment. METHODS: this study retrospectively enrolled 94 patients with Gd-EOB-DTPA enhanced MRI combined with T1 mapping, divided into group A (grade A, n=73), group B (grade B, n=14) and group C (grade C, n=7) based on Child-Pugh classification. Liver T1 relaxation times on plain scan (T1P) and hepatocellular phase (T1E) were measured. Decrease in T1 (T1D) and the percentage of decrease in T1 (T1D%) were calculated as follows: T1D=T1P-T1E, T1D%= T1D/T1P×100%. The relationship between T1P, T1E, T1D, T1D% and liver function classification was analyzed. RESULTS: T1P, T1D, and T1D% in group A were significantly higher than those of group B and C. T1E in group A was lower than those of group B and C. T1D% was significantly different between group B and C. There was no significant difference in T1P, T1E, T1D between groups B and C. T1E was positively correlated with liver function levels, T1P and T1D had a negative correlation with liver function levels. T1P, T1E, T1D, T1D% were significantly different between cirrhotic and non-cirrhotic groups. T1D% of less than 70% suggests liver dysfunction. CONCLUSION: Gd-EOB-DTPA enhanced liver MRI combined with T1 mapping is feasible for quantitative assessment of hepatic function.
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Meios de Contraste , Fígado , Humanos , Estudos Retrospectivos , Estudos de Viabilidade , Fígado/diagnóstico por imagem , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: We present a new technique that allows an intraocular lens to be explanted through the small incisions used in modern cataract surgery. METHODS AND RESULTS: The intraocular lens optic is cut into three connected pieces at the 1-mm-wide end with scissors. Then, with the stabilizing counterforce provided by a pair of vitreoretinal forceps through a paracentesis, the middle piece is removed first, followed by the two side pieces connected with haptics flipped over at the connected part. These two parts overlap each other when passing through the incision, eventually resulting in the explantation of the intraocular lens, as an intact piece. CONCLUSION: We believe this method provides a simple and effective way to remove intraocular lens through very small incisions, which could also reduce complications and hasten patient's recovery.
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Extração de Catarata , Lentes Intraoculares , Humanos , Reoperação , Remoção de Dispositivo/métodos , OlhoRESUMO
Introduction: Migraine is a neurovascular disorder that affects the quality of life of more than 1 billion people worldwide. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation tool that uses pulsed magnetic fields to modulate the cerebral cortex. This meta-analysis ascertained the therapeutic or preventive effect of rTMS on chronic migraine. Methods: We performed a database search of PubMed, Web of Science, Embase, and the Cochrane Library from January 2004 to December 2021. Eligible studies included randomized controlled studies of the analgesic effects of rTMS in patients with chronic migraine. Results: Eight studies were included. Random effects analysis showed an effect size of -1.13 [95% confidence interval (CI): -1.69 to -0.58] on the frequency of migraine attacks, indicating that rTMS was more effective for decreasing migraine attacks than the sham rTMS. Conclusions: The meta-analysis revealed that rTMS is an effective approach for reducing migraine attack when the dorsolateral prefrontal cortex was stimulated. However, rTMS may not be suggested as a method to reduce the pain level. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021228344.
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Hepatocellular carcinoma (HCC) is a malignant tumor originating from liver epithelial cells with a high clinical mortality rate. ß-Patchoulene (ß-PAE) is a compound extracted from patchouli, which has analgesic, anti-inflammatory and antioxidant effects. This research aims to probe the impacts of ß-PAE on hypoxia-induced HCC cell proliferation and epithelial-mesenchymal transition (EMT). Firstly, hypoxic injury models were constructed in HCC Huh-7 and MHCC97 cells, and the hypoxic injury cell models were then treated with different concentrations of ß-PAE. The cell viability, proliferation, migration, invasion and apoptosis were checked by the cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay, flow cytometry and terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of Survivin protein, EMT markers and the NF-κB/HIF-1α pathway was gauged by Western blot (WB) or cellular immunofluorescence or reverse transcription-polymerase chain reaction (RT-PCR). The in-vivo experiment was conducted to confirm the anti-tumor role of ß-PAE. As a result, ß-PAE abated hypoxia-induced HCC cell growth, proliferation, migration, invasion and EMT and facilitated apoptosis in vitro and in vivo dose-dependently. Further mechanism studies displayed that ß-PAE inactivated the NF-κB/HIF-1α pathway, and HIF-1α activation significantly reversed the ß-PAE-mediated tumor inhibition. ß-PAE repressed the proliferation and EMT of hypoxia-induced HCC cells by choking the NF-κB/HIF-1α pathway, suggesting that ß-PAE was a potential drug for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Hipóxia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Sesquiterpenos de Guaiano , Transdução de SinaisRESUMO
Accumulating signs have found that long noncoding RNAs (lncRNAs) contribute to hepatocellular carcinoma (HCC). Here, we probed the effect and mechanism of lncRNA DARS-AS1 in HCC. The profiles of DARS-AS1 and Cytoskeleton associated protein 2 (CKAP2) in 50 HCC tissues and non-tumor tissues were examined by real-time quantitative polymerase chain reaction (RT-qPCR). DARS-AS1 and CKAP2 overexpression and/or knockdown cell models were established. The proliferation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) were determined. CKAP2, and focal adhesion kinase (FAK)-extracellular signal-regulated kinase (ERK) was tested by Western blot (WB). The relationship between DARS-AS1 and CKAP2 was predicted by Bioinformatics, and the dual-luciferase reporter assay was applied to verify the targeting association between miR-3200-5p and DARS-AS1 and CKAP2. DARS-AS1 was overexpressed in HCC tissues (vs. that in non-tumor tissues) and was closely correlated with the patients' tumor stage. DARS-AS1 facilitated HCC cell proliferation and hampered apoptosis. HCC cell migration and EMT were enhanced by DARS-AS1. DARS-AS1 up-regulated CKAP2, which aggravated HCC. Further investigation illustrated that either DARS-AS1 or CKAP2 activated FAK-ERK pathway, and miR-3200-5p was competitively restrained by DARS-AS1. miR-3200-5p exerted tumor-suppressive effects in HCC and inactivated CKAP2 and FAK-ERK pathway. All in all, this study corroborates that DARS-AS1 facilitates HCC proliferation and metastasis by regulating miR-3200-5p-mediated CKAP2, which provides a potential target for HCC diagnosis and treatment.Abbreviations: CCK-8: cell counting kit-8; CKAP2: Cytoskeleton associated protein 2; cDNA:complementary DNA; DAPI: 4',6-diamidino-2-phenylindole; DARS-AS1: DARS1 antisense RNA 1; DEPC: diethyl pyrocarbonate; DMEM-F12: Dulbecco's minimal essential medium/Ham's-F12; EMT: epithelial-mesenchymal transition; ERK: extracellular signal-regulated kinase; FAK: focal adhesion kinase; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HCC: hepatocellular carcinoma; HE: hematoxylin-eosin; IHC: Immunohistochemistry; LIHC: Liver hepatocellular carcinoma; lncRNAs: long noncoding RNAs; MIAT: lncRNA myocardial infarction-related transcripts; MT: Mutant; NC: negative control; PBS: phosphate-buffered saline; PMSF: Phenylmethylsulfonyl fluoride; PVDF: polyvinylidene difluoride; RT: room temperature; RT-qPCR: real-time quantitative polymerase chain reaction; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SPF: specific pathogen-free; TMAP: tumor-associated microtubule-associated protein; TUNEL: TdT-mediated dUTP nick end labeling; V: volume; WT: wild type.
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Carcinoma Hepatocelular/patologia , Proteínas do Citoesqueleto/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Regulação para CimaRESUMO
Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP-4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV-MSC) and ASOs for the treatment of HD. Our results show that Cy3-labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP-4-/- as compared with wild-type mice. Downregulation of the AQP-4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF-κB) p65. IV-MSC treatment restored AQP-4 M23 expression, attenuated astrogliosis, and decreased NF-κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV-MSC is a novel strategy for improving the potency of ASO in the treatment of HD.
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Aquaporina 4/metabolismo , Doença de Huntington/genética , Células-Tronco Mesenquimais/metabolismo , Oligonucleotídeos Antissenso/genética , Adulto , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Pessoa de Meia-IdadeRESUMO
We study the conventional electron-phonon mediated superconducting properties of hole-doped black phosphorus by density functional calculations and get quite a large electron-phonon coupling (EPC) constant λ ~ 1.0 with transition temperature T C ~ 10 K, which is comparable to MgB2 when holes are doped into the degenerate and nearly flat energy bands around the Fermi level. We predict that the softening of low-frequency [Formula: see text] optical mode and its phonon displacement, which breaks the lattice nonsymmorphic symmetry of gliding plane and lifts the band double degeneracy, lead to a large EPC. These factors are favorable for BCS superconductivity.
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OBJECTIVE: To investigate the prevalence and features of ocular allergy (OA) and comorbidities among school children in Shanghai, China. METHODS: This was a population-based cross-sectional study. Each participant completed an ISAAC-based questionnaire. The prevalence of OA symptoms, allergic rhinitis (AR) asthma, atopic dermatitis (AD), and sensitization to mites, pollen, and food was analyzed. RESULTS: A total of 724 and 942 completed questionnaires from the 7-9-year-old (young group) and the 12-14-year-old (teen group) groups were analyzed, respectively. The overall prevalence of OA symptoms was 28%. However, more young students (10.6%) reported mild to severe daily life interference caused by OA than the teens (5.7%). The young group had higher prevalence of diagnosed allergic conjunctivitis (10.2%). The overall prevalence of AR symptom, diagnosed asthma, and diagnosed AD was 40.4%, 11.6%, and 16.7%, respectively. Young children had higher prevalence of diagnosed AR and AD than the teens. There were gender associated differences in the prevalence of AR and asthma among young children, but not among the teens. The comorbidities associated with OA was also analyzed. Sensitization to mites, food, and pollen was associated with higher prevalence of allergic conditions. CONCLUSIONS: OA together with other allergic conditions affected a significant number of children in Shanghai.
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Asma/epidemiologia , Conjuntivite Alérgica/epidemiologia , Dermatite Atópica/epidemiologia , Rinite Alérgica/epidemiologia , Adolescente , Alérgenos/efeitos adversos , Animais , Criança , China/epidemiologia , Conjuntivite Alérgica/patologia , Dermatite Atópica/patologia , Olho/patologia , Feminino , Hipersensibilidade Alimentar , Humanos , Masculino , Ácaros , Pólen/efeitos adversos , Rinite Alérgica/patologia , Inquéritos e QuestionáriosRESUMO
Impairment of amyloid-ß (Aß) clearance leads to Aß accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aß clearance from the brain and resist Aß injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aß. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aß injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aß accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-ß clearance from the brain through mediating the function of the glymphatic system.
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Peptídeos beta-Amiloides/toxicidade , Encéfalo/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Administração Oral , Peptídeos beta-Amiloides/administração & dosagem , Animais , Aquaporina 4/genética , Aquaporina 4/metabolismo , Astrócitos/fisiologia , Camundongos , Camundongos TransgênicosRESUMO
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial to myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis. Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice. Furthermore, rifampicin dramatically reduced the disruption of blood-brain barrier integrity, down-regulated serum concentration of IL-6 and IL-17A, inhibited pathological Th17 cell differentiation, and modulated the expression of p-STAT3 and p-p65. These results suggest that rifampicin is effective for attenuating the clinical severity of EAE mice, which may be related to its inhibitive ability in differentiation of Th17 cell and secretion of its key effector molecule IL-17A via regulation of excessive activation of the key signaling molecules of JAK/STAT pathway. Our findings may be helpful for developing therapeutic and preventive strategies for multiple sclerosis.
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Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Rifampina/uso terapêutico , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Sequência de Aminoácidos , Animais , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Rifampina/farmacologiaRESUMO
Tungsten ditelluride has attracted intense research interest due to the recent discovery of its large unsaturated magnetoresistance up to 60 T. Motivated by the presence of a small, sensitive Fermi surface of 5d electronic orbitals, we boost the electronic properties by applying a high pressure, and introduce superconductivity successfully. Superconductivity sharply appears at a pressure of 2.5 GPa, rapidly reaching a maximum critical temperature (Tc) of 7 K at around 16.8 GPa, followed by a monotonic decrease in Tc with increasing pressure, thereby exhibiting the typical dome-shaped superconducting phase. From theoretical calculations, we interpret the low-pressure region of the superconducting dome to an enrichment of the density of states at the Fermi level and attribute the high-pressure decrease in Tc to possible structural instability. Thus, tungsten ditelluride may provide a new platform for our understanding of superconductivity phenomena in transition metal dichalcogenides.
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Micro traumatic brain injury (TBI) is the most common type of brain injury, but the mechanisms underlying it are poorly understood. Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet, which plays an important role in brain edema. However, little is known about the role of AQP4 in micro TBI. Here, we examined the role of AQP4 in the pathogenesis of micro TBI in a closed-skull brain injury model, using two-photon microscopy. Our results indicate that AQP4 deletion reduced cell death, water content, astrocyte swelling and lesion volume during the acute stage of micro TBI. Our data revealed that astrocyte swelling is a decisive pathophysiological factor in the acute phase of this form of micro brain injury. Thus, treatments that inhibit AQP4 could be used as a neuroprotective strategy for micro TBI.
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Aquaporina 4/metabolismo , Lesões Encefálicas/metabolismo , Traumatismos Cranianos Fechados/metabolismo , Doença Aguda , Animais , Aquaporina 4/genética , Astrócitos/patologia , Barreira Hematoencefálica/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas/patologia , Morte Celular , Tamanho Celular , Traumatismos Cranianos Fechados/patologia , Masculino , Camundongos Knockout , Microglia/patologiaRESUMO
Semiconducting two-dimensional transition metal dichalcogenides are emerging as top candidates for post-silicon electronics. While most of them exhibit isotropic behaviour, lowering the lattice symmetry could induce anisotropic properties, which are both scientifically interesting and potentially useful. Here we present atomically thin rhenium disulfide (ReS2) flakes with unique distorted 1T structure, which exhibit in-plane anisotropic properties. We fabricated monolayer and few-layer ReS2 field-effect transistors, which exhibit competitive performance with large current on/off ratios (â¼10(7)) and low subthreshold swings (100 mV per decade). The observed anisotropic ratio along two principle axes reaches 3.1, which is the highest among all known two-dimensional semiconducting materials. Furthermore, we successfully demonstrated an integrated digital inverter with good performance by utilizing two ReS2 anisotropic field-effect transistors, suggesting the promising implementation of large-scale two-dimensional logic circuits. Our results underscore the unique properties of two-dimensional semiconducting materials with low crystal symmetry for future electronic applications.
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Raman spectra of few-layer phosphorene have been systematically studied using density functional theory calculations. We find that due to the interlayer van der Waals interactions, the low-frequency rigid layer Ag breathing mode and B1g shear mode can shift by as much as 45.1 cm(-1) and 38.5 cm(-1), respectively, as the layer numbers increase from 2L to 5L. In addition, a typical characteristic for the experimentally observable [Formula: see text] mode (~460 cm(-1) in bulk) is identified. Interestingly, this mode changes from coupled in-plane and out-of-plane vibrations in single layer to pure in-plane vibrations in a few layers and the corresponding frequencies vary by as much as over 10 cm(-1). We argue that this Raman frequency variation might be used to experimentally characterize the thickness of this intriguing 2D layered material.