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1.
Rev Esp Enferm Dig ; 1112019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595756

RESUMO

OBJECTIVES: the aim of this study was to evaluate the prognostic significance of preoperative serum lipid in patients with gallbladder cancer (GBC). METHODS: ninety-nine patients with GBC between October 2009 and December 2013 were reviewed in this retrospective study. Total serum cholesterol (TC), total triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo-A), apolipoprotein B (Apo-B) and free fatty acids (FFA) were measured before surgery. The correlation of serum lipid levels with clinical data, including gender, age, tumor size, lymph nodes metastasis, tumor differentiation, distant metastasis and TNM stage were analyzed by univariate and multivariate survival analysis to evaluate independent prognostic factors. RESULTS: compared with the normal HDL-C group (n = 57), the overall survival rate among GBC patients with low HDL-C levels (n = 42) was reduced (p < 0.05). However, there were no significant differences in overall survival for patients with different levels of TC, TG, Apo-A, Apo-B, LDL-C or FFA. The serum level of HDL-C was associated with TNM stage (p < 0.05) and distant metastasis (p < 0.001). The multivariate prognosis analysis showed that HDL-C and lymph nodes metastasis were independent prognostic factors (p < 0.05). A prognostic evaluation model based on HDL-C and lymph nodes metastasis was established. CONCLUSION: preoperative serum HDL-C level was closely associated with distant metastasis of patients with GBC. HDL-C level may be a valuable prognostic factor for GBC patients. The combination of HDLC and lymph nodes metastasis can better predict the prognosis of GBC.

2.
Int J Mol Sci ; 20(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640144

RESUMO

Progranulin (PGRN) plays a crucial role in diverse biological processes, including cell proliferation and embryonic development. PGRN can be cleaved by neutrophil elastase to release granulin (GRN). PGRN has been found to inhibit inflammation. Whereas, GRN plays a role as a pro-inflammatory factor. However, the pathophysiological roles of PGRN and GRN, at early stages after cerebral ischemia, have not yet been fully understood. The aim of this study was to obtain further insight into the pathologic roles of PGRN and GRN. We demonstrated that the amount of PGRN was significantly increased in microglial cells after cerebral ischemia in rats and that neutrophil elastase activity was also increased at an early stage after cerebral ischemia, resulting in the production of GRN. The inhibition of neutrophil elastase activity suppressed PGRN cleavage and GRN production, as well as the increase in pro-inflammatory cytokines, after cerebral ischemia. The administration of an elastase inhibitor decreased the number of injured cells and improved the neurological deficits test scores. Our findings suggest that an increase in the activity of elastase to cleave PGRN, and to produce GRN, was involved in an inflammatory response at the early stages after cerebral ischemia, and that inhibition of elastase activity could suppress the progression of cerebral ischemic injury.

3.
Chem Biol Interact ; 314: 108849, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610157

RESUMO

To provide novel insight into approaches designed to combat glioblastoma, the molecular details of the cytotoxicity of gamabufotalin, were investigated in the human glioblastoma cell line U-87. A dose-dependent cytotoxicity was observed in the cells, whereas no detectable toxicity was confirmed in mouse primary astrocytes. LDH leakage was only observed in the cells treated with a relatively high concentration (>80 ng/ml). Downregulation of the expression levels of Aurora B, cdc25A, cdc25C, cdc2, Cyclin B1 and survivin, and upregulation of the expression level of p21 were observed in treated cells and occurred in parallel with G2/M phase arrest. Treatment with gamabufotalin also downregulated the expression level of uPA, CA9, and upregulated the expression level of TIMP3, all of which are closely associated with invasion/metastasis. Autophagy induction was observed in the treated cells and the addition of wortmannin, a potent autophagy inhibitor, significantly rescued U-87 cells. These results indicate that gamabufotalin exhibits cytotoxicity against cancerous glial cells with high potency and selectivity through multiple cytotoxic signaling pathways. The activation of p38 MAPK pathway along with the upregulation of VEGF/VEGFR2 was observed in the treated cells, both of which are likely to be compensatory changes in response to gamabufotalin treatment. Intriguingly, a specific inhibitor of p38 MAPK enhanced the cytotoxicity of the drug, suggesting an important prosurvival role for p38 MAPK. We thus suggest that developing a new combination regimen of gamabufotalin plus a p38 MAPK inhibitor and/or inhibitors for VEGF/VEGFR could improve the efficacy of the drug, and may provide more therapeutic benefits to patients with glioblastoma.

4.
J Mater Chem B ; 7(37): 5713-5724, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31482931

RESUMO

The bio-inertness and inferior osseointegration of polyetheretherketone (PEEK) affect its long-term lifetime in clinical applications, and appropriate surface modification is an effective way to enhance osseointegration of PEEK implants. In the present study, a strategy of combining sulfonation with alkali treatment was proposed to endow PEEK with rapid apatite deposition and thus enhanced bioactivity. After 3 min of sulfonation with 98% H2SO4, the sample (PEEK-S-3) showed an optimized surface microporous network and obviously improved hydrophilicity. Its contact angle reduced from the original 106 ± 2.3° to 88 ± 4.0°. After a further 24 h of NaOH treatment on PEEK-S-3, Na element was introduced into the obtained sample (PEEK-Na-24), which had a similar surface morphology and chemical structure with PEEK-S-3 and had a further reduced contact angle (77.9 ± 2.9°). The in vitro bioactivity tests showed that after only 3 days of immersion in simulated body fluid (SBF), PEEK-Na-24 was fully covered with a layer of uniform bone-like apatite. The apatite deposition sharply decreased the contact angle of the sample (PEEK-HA) to 16.6 ± 2.6° and increased its surface roughness to 1.05 ± 0.27 µm, leading to the enhanced adsorption of serum proteins on PEEK-HA. The in vitro cell culture indicated that all the three surface-modified samples (PEEK-S-3, PEEK-Na-24 and PEEK-HA) could promote the adhesion, spreading, proliferation and osteoblastic differentiation of MC3T3-E1 pre-osteoblasts, and PEEK-HA presented the best effect. Thus, the surface bioactive PEEK resulting from the optimized surface modification, i.e. combination of sulfonation, alkali treatment and biomimetic apatite deposition, could have good potential in clinical application.

5.
Lab Invest ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558773

RESUMO

Electron beam (EB) irradiation is useful to reduce the recurrence of keloids; however, the underlying mechanism remains unknown. MicroRNA-21 (miR-21), which regulates autophagy during cancer radiation therapy, was identified as a potential therapeutic target for keloids. Here, we investigate the regulatory mechanism(s) of miR-21-5p on keloid fibroblast autophagy and migration after EB irradiation. The microRNA expression profile of the keloid dermis was examined by performing a microRNA microarray. Levels of LC3B and Beclin-1 were detected by immunohistochemical and western blot analysis in the keloid dermis and fibroblasts. Autophagy and apoptosis were tested in keloid fibroblasts after EB irradiation or transfection with an miR-21-5p inhibitor using electron microscopy, a Cyto-ID Green Autophagy Detection Kit, and an Annexin V PE Apoptosis Detection Kit. Migration was analyzed by an in vitro scratch-wound healing assay. Mechanistic tests were performed using small interfering RNAs to phosphatase and tensin homolog (siPTEN). Levels of miR-21-5p, PTEN, programmed cell death 4 (PDCD4), p-AKT, and apoptosis- and autophagy-associated genes were examined by qRT-PCR and western blotting. LC3B expression and migration ability were enhanced in fibroblasts and the keloid margin dermis compared with those in the adjacent normal skin. Both EB irradiation and an miR-21-5p inhibitor reduced keloid fibroblast autophagy, which was accompanied by decreased expression of miR-21-5p, p-AKT, and LC3B-II and increased expression of PTEN, PDCD4, and apoptosis-related genes. MiR-21-5p downregulation inhibited migration and suppressed LC3B expression and this was reversed by PTEN reduction. In conclusion, with increasing apoptosis, EB irradiation inhibits autophagy in keloid fibroblasts by reducing miR-21-5p, which regulates migration and LC3B expression via PTEN/AKT signaling. These data suggest a potential mechanism wherein miR-21-5p inhibition regulates autophagy and migration in EB-irradiated keloid fibroblasts, effectively preventing local invasion and recurrence. Therefore, miR-21-5p could be a new therapeutic target, to replace EB irradiation, and control keloid relapse.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31535347

RESUMO

This study investigates the relationships between depression and cognitive performance among older adults living in Shandong province. Data were derived from the World Health Organization's Study on global AGEing and adult health (WHO-SAGE) China Wave 1 aged 50 and over residing in Shandong province (n = 1926). Cognitive performance was assessed by overall cognitive score. Data were analysed by multivariate linear regression. In rural Shandong, having a history of depression (- 4.0; p < 0.001), female (- 9.3; p < 0.001), and poor household wealth (- 8.9; p < 0.001) and primary level of education (- 6.4; p < 0.001) were main factors associated with their poor cognitive performance. Notably, in urban Shandong, lowest household wealth (- 12.5; p < 0.001) and not having health insurance (- 9.7; p < 0.001) were significant predictors of adverse cognitive performance. Findings could help inform policy in monitoring depressive symptoms and cognitive performance among older adults in China.

7.
J Hazard Mater ; 383: 121162, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31520933

RESUMO

Sulfur dioxide (SO2), nitric oxide (NO) and elemental mercury (Hg0) are three common air pollutants in flue gas. SO2 and NO are the main precursors for chemical smog and Hg0 is a bio-toxicant for human. Cooperative removal of multi-air-pollutant in flue gas using radical-induced oxidation reaction is considered as one of the most promising methods due to the high removal efficiency, low cost and less secondary environmental impact. The common radicals used in air pollution control can be classified into four types: (1) hydroxyl radical (OH), (2) sulfate radical (SO4-), (3) chlorine-containing radicals (Cl, ClO2, ClO, HOCl-, etc.) and (4) ozone. This review summarizes the generation methods and mechanism of the four kinds of radicals, as well as their applications in the removal of multi-air-pollutant in flue gas. The reactivity, selectivity and reaction mechanism of the four kinds of radicals in multi-air-pollutant removal were comprehensively described. Finally, some future research suggestions on the development of new technique for cooperative removal of multi-air-pollutant in flue gas were provided.

8.
J Hazard Mater ; 383: 121135, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31542692

RESUMO

We developed a novel method, microwave (MW) induced ultraviolet (UV) irradiating H2O/O2, to cooperatively remove NO and Hg0, with the efficiencies of 89.3% and 99.5%. It also can remove 97% SO2. O2 at a content of 2-8% was sufficient to conduct a good removal of NO and Hg0. Ozone (O3) and hydroxyl radical (HO•) were proved to be the major oxidants for the removal of Hg0 and NO, respectively. High temperature facilitated NO removal but impaired Hg0 removal. SO2 greatly promoted the removal of NO and Hg0 due to the formation of SO4•-. The presence of Cl- and Br-suppressed NO removal but promoted Hg0 removal, because Cl- and Br-quenched HO• to produce Cl- and Br-radicals. The produced NO2 could be totally absorbed by the Na2SO3 solution that followed the main reactor. The O3 yield and the formation of HO• under different conditions were determined using iodine quantity method and electron spin resonance (ESR). The distributions of anion concentration and mercury proportion were obtained using ion chromatography (IC) and cold atom fluorescence spectrometry (AFS), and the main products were identified to be SO42-, NO3- and HgO. The mechanisms of removal of SO2, NO and Hg0 were speculated.

9.
Biomater Sci ; 7(11): 4748-4757, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31508613

RESUMO

Multidrug resistance (MDR) is one of the main reasons for the inefficiency of cancer chemotherapy. As a consequence of MDR, the expression level of membrane proteins might be changed, which can thus be used to develop a novel strategy for its treatment. Based on the high overexpression of Y1 receptor (Y1R) protein and P-glycoprotein (P-gp) in the multidrug resistant breast cancer cell line, a selective Y1R ligand [Asn6, Pro34]-NPY (AP) was employed to stabilize the chemotherapeutic drug doxorubicin (DOX) and P-gp inhibitor tariquidar (Tar) co-loaded nanomicelles at the physiological level. This also improved the targeted delivery of DOX and Tar into MCF-7/ADR cells. Co-delivered Tar further impedes the efflux of DOX and enhances its accumulation in the nuclei of drug resistant cancer cells, thereby inducing significant inhibition of cell growth. The synergistic effect of AP and Tar generates an excellent in vivo tumor targeting and antitumor efficacy of DOX with prolonged survival and minimized side effects, especially for liver metastasis. In general, Y1R as a novel target site and its selective ligand AP synergized with the P-gp inhibitor can be used for a more precise MDR breast cancer treatment.

10.
Clin Exp Rheumatol ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31498070

RESUMO

OBJECTIVES: The interface between pro-inflammatory cytokines and rheumatoid synovial fibroblast (sFLS) has central effects on rheumatoid arthritis (RA). The present study aimed to explore the role of IL-34 expression as one of major cytokine implicated in RA. METHODS: We examined the expression of IL-34 after RA sFLS stimulated by IL-1ß and TGF-ß1 separately by reverse transcription polymerase chain reaction (RT-PCR). Transwell and wound closure techniques were used to detect whether IL-34 is involved in promoting cell migration. Cellular viability was determined via CCK-8 and cultural morphology assays between IL-34 downregulated group and non-transfected counterpart. We also tested the expression of VEGF gene with RT-PCR analysis and activation of the major signalling pathways by western blot in IL-34 down-regulated group, IL-1ß or TGF-ß1 treated groups. Propidium iodide (PI) staining and fluoresceine isothiocyanate (FITC) Annexin V and propidium iodide apoptosis assay were used to analyse cell cycle arrest and apoptosis separately in IL-34 down-regulated cells. RESULTS: We found that IL-1ß significantly enhanced IL-34 expression, while contrarily, TGF-ß1 restrained IL-34 gene expression. Transwell and wound closure techniques showed that IL-34 was involved considerably in promoting cell migration. However, IL-34 knock-down restricted sFLS migration possibly through the diminishing of MMP2 and MMP9 expression. Interestingly, IL-34 down-regulated cells exhibited significantly low cellular viability compared with the non-transfected counterpart via CCK-8 and cultural morphology assays. We found that IL-34 down-regulated cells have low VEGF gene expression compared with treated cells. PI staining showed a G0/G1 cell cycle arrest in IL-34 down-regulated cells. FITC Annexin V and propidium iodide apoptosis assay verified that IL-34 down-regulated cells induced massive apoptosis through apoptotic signalling caspase3, while IL-1ß treated cells presented termination of cellular apoptosis signalled by BCL-2. Furthermore, we observed IL-34 induced activation of ERK1/2 and AKT pathways while IL-34 down-regulation significantly decreased the activation of these pathways. CONCLUSIONS: Our data add novel insights into the pathogenesis of RA and we suggest that IL-34 plays a dominant role in controlling migration and proliferation of sFLS. Consequently, therapeutic strategies targeting IL-34 could be a potent therapy for RA.

11.
Ying Yong Sheng Tai Xue Bao ; 30(9): 3203-3214, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31529896

RESUMO

To investigate the traditional village living environment adaptability to desertification and topography, the suitability evaluation index system and weight of traditional Buyei traditional villages in the rocky desertification area human settlement were quantified using Delphi method and comprehensive weighting method. We calculated human settlements environment suitability value and threshold to comprehensively analyze the human settlements environment suitability. The results showed that 10% of the traditional Buyei traditional villages were located in the rocky desertification areas with high intensity and extremely high intensity and had the tradition of selecting the best environment. The index system of residential environment suitability was composed of five first-level indices (economy, historic culture, ecology, society, and building environment suitability) and 26 second-level indices. This index system was applicable to villages in karst regions. The comprehensive environmental suitability value (2.81-3.77), the economy value (0.77-1.17), the historic culture value (0.39-0.50), the ecology value (0.83-1.07), the social environment value (0.38-0.53) all decreased with the increasing intensity of rocky desertification, but the suitability value of building environment did not change, which ranged from 0.43 to 0.51. Rocky desertification had profound and synergistic impacts on economy, historic culture, ecology and social environment. The floor level of the human settlement suitability threshold was 2.93. If the threshold was lower than 2.93, it could be considered to move or take measures to improve its value. The suitability value (3.56) of traditional village living environment in mountain slope was higher than that in depression (3.42) and valley (3.16). The human settlement suitability of traditional villages in rocky desertification area was higher than that of ordinary villages, but was lower than that of normal landform, with the differences in economy and ecology being the main reasons. To improve the living environment of traditional villages in rocky desertification areas, we should strengthen the comprehensive control of rocky desertification and policy support, develop ecological economy and tourism, protect historic culture or choose ecological migration. This research could provide theoretical base for the planning and construction of village living environment protection in karst areas.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Secas , Ecologia , Humanos
12.
Int J Mol Sci ; 20(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461846

RESUMO

Affinity maturation and rational design have a raised importance in the application of nanobody (VHH), and its unique structure guaranteed these processes quickly done in vitro. An anti-CD47 nanobody, Nb02, was screened via a synthetic phage display library with 278 nM of KD value. In this study, a new strategy based on homology modeling and Rational Mutation Hotspots Design Protocol (RMHDP) was presented for building a fast and efficient platform for nanobody affinity maturation. A three-dimensional analytical structural model of Nb02 was constructed and then docked with the antigen, the CD47 extracellular domain (CD47ext). Mutants with high binding affinity are predicted by the scoring of nanobody-antigen complexes based on molecular dynamics trajectories and simulation. Ultimately, an improved mutant with an 87.4-fold affinity (3.2 nM) and 7.36 °C higher thermal stability was obtained. These findings might contribute to computational affinity maturation of nanobodies via homology modeling using the recent advancements in computational power. The add-in of aromatic residues which formed aromatic-aromatic interaction plays a pivotal role in affinity and thermostability improvement. In a word, the methods used in this study might provide a reference for rapid and efficient in vitro affinity maturation of nanobodies.

13.
Environ Sci Technol ; 53(18): 10835-10844, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31441649

RESUMO

Bromo-chloro alkenes (Br-Cl PXAs) have been used for over 30 years as flame retardants and are listed on several national chemical inventories. Very little publicly available information is available on Br-Cl PXAs, and thus preliminary ecological risk screening is challenging due to the lack of basic information such as molecular structure and associated physicochemical properties. Due to their likely similarity with chlorinated paraffins (CPs), Br-Cl PXAs may pose a similar environmental hazard. Several structural databases list such substances as "alkenes", although the industrial synthesis involves halogenation of linear alpha-olefins and would be expected to produce linear alkanes. In this study, a combination of high-resolution separation and mass spectrometric techniques were used to characterize a Br-Cl PXA industrial technical product, C12-30 bromo-chloro alpha-alkenes (CAS RN 68527-01-5). The results show this product is dominated by C18 carbon chain lengths, substituted with 3-7 chlorine atoms and 1-3 bromine atoms on an alkane chain. Long-chain C18 chlorinated paraffins are also present, although they represent a relatively minor component. Experimental log KOW (6.9 to 8.6) and estimated log KOA (10.5 to 13.5) and log KAW (-5.1 to -0.6) partition coefficients suggest that this chemical will behave similarly to medium- and long-chain CPs as well as other persistent organic pollutants, such as highly chlorinated pesticides and polychlorinated biphenyls. The results of this study provide an initial step toward understanding the environmental behavior and persistence of Br-Cl PXAs, highlighting the need for further assessment and re-evaluation of the current structure(s) assigned to these compounds.

14.
Sci Rep ; 9(1): 11782, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409872

RESUMO

The N-methyl-D-aspartate (NMDA) receptor has been implicated in several neurodegenerative diseases, including stroke. Low-density lipoprotein receptor-related protein 1 (LRP1) plays pivotal roles in endocytosis and signaling in the cell. Immature LRP1 is processed by furin in the trans-Golgi network (TGN) and transported to the cell surface as its mature form. Activation of mature LRP1 exerts a protective effect against glutamate-induced degeneration of the rat retinal ganglion cells, as was shown in our previous study. However, the roles of LRP1 in the pathogenesis of excitotoxic neuronal injuries remain to be determined. The aim of this present study was to achieve further insight into the pathophysiologic roles of LRP1 after excitotoxic neuronal injuries. Our findings are the first to demonstrate that LRP1 was significantly cleaved by furin after cerebral ischemia in rats as well as after exposure of cultured cortical neurons to NMDA. It was noteworthy that the intracellular domain (ICD) of LRP1 was co-localized with TGN and furin. Furthermore, a furin inhibitor inhibited the cleavage of LRP1 and co-localization of LRP1-ICD with TGN or furin. Our findings suggest that furin-mediated cleavage of LRP1 and changes in the localization of LRP1-ICD were involved in the excitotoxic neuronal injury.

15.
BMC Complement Altern Med ; 19(1): 216, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412862

RESUMO

BACKGROUND: Breast cancer is still the most common malignant tumor that threatens the female's life in the world, especially triple-negative breast cancer (TNBC), one of the most difficult subtypes. Lack of targeted therapies brings about urgent demand for novel treatments. In this study we aim to investigate the anti-tumor activity of Berberine (BBR), a Chinese plant-derived alkaloid, against the TNBC cell line MDA-MB-231 and elucidate its mechanism referring to anti-inflammation. METHODS: Cell inhibition rate was measured by Cell Proliferation Assay, the cytotoxic effects was detected by Lactate dehydrogenase (LDH) leakage assay, the colony formation and migration potential were evaluated by colony formation assay and wound healing assay, the release of inflammatory cytokines was detected by EMD multifactor detection, and alterations of proteins and genes related to the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway were analyzed using western blotting and real-time Polymerase Chain Reaction (PCR). RESULTS: BBR reduce the viability of MDA-MB-231 cells and increased the release of LDH from the cells in a dose-dependent manner, with and inhibition of colony formation potential and migration of the cells. BBR also caused a marked reduction in the secretion of proinflammatory cytokines, Interleukin-1α (IL-1α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Besides, a down-regulated behavior was observed with the expression of P2X purinoceptor 7 (P2X7), NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1 p20, Interleukin-18 (IL-18), IL-1ß proteins and NLRP3, Caspase-1 and ASC mRNAs in the NLRP3 inflammasome cascade. CONCLUSIONS: Our results confirmed that BBR can effectively affect both tumor outgrowth and spontaneous metastasis in TNBC, and that we identified a new mechanism associated with inhibition the NLRP3 inflammasome pathway, suggesting its potential therapeutic relevance in clinical use.

16.
Zhen Ci Yan Jiu ; 44(6): 405-11, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368262

RESUMO

OBJECTIVE: To observe the influence of scalp acupuncture on cerebral infarct size and expression of IL-10, IL-6, and IL-1ß in the para-hippocampal gyrus in acute ischemic cerebrovascular disease(AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to normal control (control), AICD model, medication, and scalp acupuncture groups (n=12 per group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the medication group received intraperitoneal injection of Ammonium 1-Pyrrolidinedithiocarbamate (APDC, 100 mg•kg-1•d-1), once daily for 7 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 7 days. Before and after intervention, the neurologic deficit score (NDS) and the neurological score (NS) were evaluated according to Longa's and Schäbitz's methods, respectively. At the end of the intervention, the para-hippocampal gyrus and whole brain were collected respectively. The expression levels of IL-10, IL-6 and IL-1ß in the para-hippocampal gyrus tissue were detected by immunohistochemistry, and the cerebral infarct volume of the brain was detected by triphenyltetrazollium chloride (TTC) staining after sectioning. RESULTS: Following modeling, the NDS, NS and the expression of IL-10, IL-6 and IL-1ß in para-hippocampal gyrus were significantly increased in the model group compared with the control group (P<0.01). After the intervention, the NDS, NS and infarct volume, and the expression levels of IL-6 and IL-1ß in the para-hippocampal gyrus were significantly decreased in both medication and scalp acupuncture groups compared with the model group (P<0.05), and the expression of IL-10 was further obviously up-regulated in the scalp acupuncture group (P<0.05) rather than in the medication group (P>0.05). The effect of scalp acupuncture was obviously superior to that of medication in up-regulating IL-10 expression level (P<0.05). No significant differences were found between the medication and scalp acupuncture groups in the levels of NDS, NS, infarct volume, IL-6 and IL-1ß proteins (P>0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce infarct volume in AICD rats, which may be associated with its function in up-regulating the expression of IL-10 and in inhibiting the expression of IL-6 and IL-1ß to reduce inflammation reaction.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Animais , Interleucina-10 , Interleucina-1beta , Interleucina-6 , Masculino , Giro Para-Hipocampal , Ratos , Ratos Sprague-Dawley , Couro Cabeludo
17.
Chaos ; 29(7): 073119, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31370406

RESUMO

The steady state motion visual evoked potential (SSMVEP)-based brain computer interface (BCI), which incorporates the motion perception capabilities of the human visual system to alleviate the negative effects caused by strong visual stimulation from steady-state VEP, has attracted a great deal of attention. In this paper, we design a SSMVEP-based experiment by Newton's ring paradigm. Then, we use the canonical correlation analysis and Support Vector Machines to classify SSMVEP signals for the SSMVEP-based electroencephalography (EEG) signal detection. We find that the classification accuracy of different subjects under fatigue state is much lower than that in the normal state. To probe into this, we develop a multiplex limited penetrable horizontal visibility graph method, which enables to infer a brain network from 62-channel EEG signals. Subsequently, we analyze the variation of the average weighted clustering coefficient and the weighted global efficiency corresponding to these two brain states and find that both network measures are lower under fatigue state. The results suggest that the associations and information transfer efficiency among different brain regions become weaker when the brain state changes from normal to fatigue, which provide new insights into the explanations for the reduced classification accuracy. The promising classification results and the findings render the proposed methods particularly useful for analyzing EEG recordings from SSMVEP-based BCI system.

18.
Biochem Biophys Res Commun ; 518(4): 638-643, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31451218

RESUMO

Keloid, marked by excessive deposition of extracellular matrix components, usually occurs after cutaneous trauma. The molecular mechanism involved in the etiology of keloid remains largely unknown in spite of extensive studies presented on the mechanism of Keloid. NEDD4 has come to be recognized as a potential mediator implicated in inflammation and keloid that could chronically develop. Despite this, the working mechanism of NEDD4 involved in keloid remains unclear. In our present report, STAT3 was identified as a novel transcriptional factor that can diametrically regulate the transcription of NEDD4 and the translation that ensues. The regulation by STAT3 over NEDD4 can be abolished as long as the p-STAT3 was inactivated in the presence of Niclosamide, a kind of inhibitors that work specifically on STAT3 signaling pathway. In turn, silencing of NEDD4 was also shown to be able to down-regulate the expression of p-STAT3. No direct protein-protein interactions between STAT3 and NEDD4 can be identified in our setting. The data we provided herein enrich the knowledge regarding the molecular mechanism of NEDD4 involved in the pathogenesis of keloid, defining a new regulatory role for STAT3 in keloid.

19.
Exp Cell Res ; 383(2): 111546, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398352

RESUMO

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

20.
J Cell Mol Med ; 23(10): 6554-6564, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402547

RESUMO

Osteoarthritis (OA) is a prevalent degenerative joint disease whose pathogenesis remains unclear. The research aims to investigate the roles of Circ_0136474/miR-127-5p/MMP-13 axis in OA. Differentially expressed circRNAs and miRNAs in OA cartilage tissue were screened out and visualized by R project based on RNA-seq data and microarray data respectively. qRT-PCR was carried out for detection of relative expression levels of Circ_0136474, miR-127-5p, MMP-13 and other inflammatory factors and Western blot analysis was conducted to detect the protein expression level of MMP-13. CCK-8 assay and flow cytometry were conducted to determine cell proliferation and cell apoptotic ability respectively. RNA-fluorescence in situ hybridization (RNA-FISH) experiments were conducted to confirm the immune-localization of the Circ_0136474 and MMP-13 in human tissues. Targeted relationships were predicted by bioinformatic analysis and verified by dual-luciferase reporter assay. Our findings revealed that the expression levels of both Circ_0136474 and MMP-13 in OA cartilage tissue were significantly higher than that in normal cartilage tissue. Circ_0136474 could suppress cell proliferation by facilitating MMP-13 expression and suppressing miR-127-5p expression in OA. Overexpression of miR-127-5p negatively regulated MMP-13 expression to enhance cell proliferation. Our study demonstrated that Circ_0136474 and MMP-13 suppressed cell proliferation, while enhanced cell apoptosis by competitive binding to miR-127-5p in OA, which may well provide us with a new therapeutic strategy for osteoarthritis.

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