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1.
Exp Neurol ; 327: 113215, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991126

RESUMO

Neurogenic differentiation 1 (NeuroD1) is mainlyexpressed in developing neurons where it plays critical roles in neuronal maturation and neurite elongation. The potential role and mechanism of NeuroD1 in adult axonal regeneration is not clear. The present study used synapsin (SYN) Cre and AAV9-Flex vectors to conditionally overexpress NeuroD1 in adult spinal neurons and found that NeuroD1 overexpression significantly accelerated axonal regeneration and functional recovery after sciatic nerve injury. Further in vitro and in vivo experiments suggested that the mechanism of NeuroD1 promotion on axonal regeneration was related to its regulation of the expression of neurotrophin BDNF and its receptor TrkB as well as a microtubule severing protein spastin.

2.
Cells ; 9(1)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963385

RESUMO

RhoA-GTPase (RhoA) is widely regarded as a key molecular switch to inhibit neurite outgrowth by rigidifying the actin cytoskeleton. However, during neurite outgrowth, whether and how microtubule dynamics are regulated by RhoA remains to be elucidated. Herein, CT04 and Y27632 were used to inactivate RhoA and its downstream effector Rho-associated coiled coil-forming kinase (ROCK), while the RhoAQ63L lentiviral vector was utilized to overexpress the constitutively activated RhoA in dorsal root ganglion (DRG) neurons or neuronal differentiated PC12 cells. The current data illustrate that the RhoA signaling pathway negatively modulates neurite outgrowth and elevates the expression of Glu-tubulin (a marker for a stabilized microtubule). Meanwhile, the microtubule-severing proteins spastin and p60-katanin were downregulated by the RhoA signaling pathway. When spastin and p60-katanin were knocked down, the effects of RhoA inhibition on neurite outgrowth were significantly reversed. Taken together, this study demonstrates that the RhoA pathway-mediated inhibition of neurite outgrowth is not only related to the modulation of microfilament dynamics but is also attributable to the regulation of the expression of spastin and p60-katanin and thus influences microtubule dynamics.

3.
Front Pharmacol ; 10: 1307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736765

RESUMO

Background: The increasing prevalence of extensively drug-resistant Klebsiella pneumoniae (XDR-KP) poses a serious threat to clinical anti-infective treatment. This retrospective study assessed the molecular epidemiology of and risk factors for infections with XDR-KP to investigate the mechanism of drug resistance and the epidemiological characteristics. Methods: A retrospective 1:2 case-control study was conducted at Chongqing Renji Affiliated Hospital of the Chinese Academy of Sciences University from January 2015 to December 2017. A total of 69 non-repetitive XDR-KP strains were collected. Patients infected with XDR-KP comprised the case group, and 138 matched patients with non-XDR-KP infection at the same site comprised the control group. The chi-square test and logistic regression were performed to evaluate the related risk factors. Molecular typing was performed by multilocus sequence typing (MLST). Potential resistance genes were detected by polymerase chain reaction (PCR) and sequencing. Predictors of 28-day mortality in patients with XDR-KP infection were also identified in our study. Results: Only tigecycline and polymyxin B showed favorable in vitro drug sensitivity tests. These XDR-KP strains had a high prevalence rate (n = 66, 95.7%) of carbapenemase-related drug resistance genes. Among them, KPC-2 was the most frequently detected gene (n = 52, 75.4%). Particularly, all of the isolates harbored multiple drug resistance genes. Epidemiological analysis showed that fifty-eight XDR-KP isolates were resistant strains with the ST-11 genotype. Multivariate logistic regression analysis showed that ICU admission (OR: 3.28, 95% CI: 1.66-6.49, P < 0.001), tracheal cannula (OR: 3.16, 95% CI: 1.48-6.76, P = 0.003), and carbapenem exposure (OR: 3.16, 95% CI: 1.25-7.98, P = 0.015) were independent risk factors for XDR-KP infection. Solid tumors (OR: 7.22, 95% CI: 1.84-28.34, P = 0.005) and septic shock (OR: 9.46, 95% CI: 2.00-44.72, P = 0.005) were independent risk factors for 28-day mortality from XDR-KP infection. Conclusion: This study showed that XDR-KP isolates were highly resistant and exhibited clonal transmission. ST11 was the predominant epidemic type of XDR-KP producing KPC-2 in Southwestern China. Physicians should be aware of these high-risk patients with notable predictive factors for XDR-KP infection. These findings may provide some recommendation for the diagnosis and treatment of patients infected with XDR-KP strains in Southwestern China.

4.
Cogn Neurodyn ; 13(5): 475-488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31565092

RESUMO

Memristor is a nanoscale circuit element with nonvolatile, binary, multilevel and analog states. Its conductance (resistance) plasticity is similar to biological synapses. Information sparse coding is considered as the key mechanism of biological neural systems to process mass complex perception data, which is applied in the fields of signal processing, computer vision and so on. This paper proposes a soft-threshold adaptive sparse coding algorithm named MMN-SLCA based on the memristor, neural network and sparse coding theory. Specifically, the memristor crossbar array is used to realize the dictionary set. And by leveraging its unique vector-matrix operation advantages and biological synaptic characteristic, two key compositions of the sparse coding, namely, pattern matching and lateral neuronal inhibition are realized conveniently and efficiently. Besides, threshold variability further enhances the adaptive ability of the intelligent sparse coding. Furthermore, a hardware implementation framework of the sparse coding algorithm is designed to provide feasible solutions for hardware acceleration, real-time processing and embedded applications. Finally, the application of MMN-SLCA in image super-resolution reconstruction is discussed. Experimental simulations and result analysis verify the effectiveness of the proposed scheme and show its superior potentials in large-scale low-power intelligent information coding and processing.

5.
J Hazard Mater ; 380: 120905, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31349144

RESUMO

Valuable metals such as manganese, cobalt, nickel and copper are recycled from spent ternary lithium-ions batteries (LiBs) and are considered as the active metal precursor to prepare based-manganese multi oxide for VOCs oxidation. The results of characterization analysis indicate that the catalyst from spent LiBs shows larger specific surface area of 26.80 m2/g as well as abundant mesoporous structures on the surface, higher molar ratio of Mn4+/Mn3+ (0.70) and Olatt/Oads (1.68), better low-temperature reductivity and stronger intensity of weak acid sites in comparison with those of pure manganese oxides. The evaluation experiments show that the catalyst from waste exhibits more excellent catalytic performance of toluene combustion in comparison with pure manganese oxides. Furthermore, the presence of considerable amount of lithium and aluminum ions can severely weaken the catalytic activity while the co-existence of nickel, cobalt and copper ions contribute a lot to facilitate the catalytic behavior. In-situ DRIFT study implies that the introduction of lithium, aluminum, nickel, copper and cobalt into pure manganese oxides can facilitate toluene conversion to various extents, following the consecutive steps via benzyl species, benzoyl oxide species, benzaldehyde species, benzoate species and the primary intermediates are benzoate species.

6.
Sci Total Environ ; 684: 265-275, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31153073

RESUMO

Herein we explored the co-transport behaviors of cadmium (Cd2+) with biochar-Fe3O4 nanocomposites (BFNCs) (and biochar-alone for comparison) in water-saturated natural soil (paddy soil and red soil) packed columns. The BFNCs promoted the transport of Cd2+ (Cd2+ mass recovery = 2.71-10.5%) by 2.5-times in soils, compared to the biochar-alone (Cd2+ mass recovery = 1.28-4.07%). Greater interplays via electrostatic attraction, complexation with hydroxyls, and π-π interaction with the aromatic complexes altogether contributed to the higher adsorption capacity and transport potential towards Cd2+ by the BFNCs (vs. biochar-alone). The BFNCs greatly increased (27.1-95.5 times) Cd2+ transport in soils mainly through BFNC-Cd2+ complexes, compared to the negligible transport of Cd2+ in soils without presence of BFNCs. Higher mobility of BFNCs and BFNC-Cd2+ complex occurred in the red soil than in the paddy soil due to the lower contents of Fe/Al oxides in the red soil. Greater enhancement effect (~2.5 times) on Cd2+ was observed by BFNCs derived from wheat straw than wood chip, due to the stronger sorption ability of wheat straw biochar towards Cd2+, likely stemming from more mineral composition such as CaCO3. Our findings suggest that the potential co-transport risks should not be simply ignored particularly when the next-generation of multifunctional biochar­iron oxide nanocomposites are employed for in-situ remediation of soils contaminated with organic/inorganic contaminants like Cd2+.


Assuntos
Cádmio/análise , Carvão Vegetal/química , Óxido Ferroso-Férrico/química , Nanocompostos/química , Poluentes do Solo/análise , Solo/química , Adsorção , Nanopartículas Metálicas/química , Água/análise
7.
Am J Reprod Immunol ; 82(3): e13159, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31206849

RESUMO

PROBLEM: The oviduct plays an indispensable role in the formation of eggs, especially the magnum and uterus. The identification of oviduct development in different stages will help to target candidate genes and pathways in regulation of albumen and eggshell formation, as well as defense mechanism in oviduct and egg. METHODS: To identify the function differences and the molecular defense mechanism of the oviduct and egg, we performed transcriptome sequencing analysis of the magnum and uterus in 120-d-old and 300-d-old Lohmann layers, three birds in each group. RESULTS: With fold changes (log2 ratio) ≥ 2 and false discovery rate (FDR) < 0.01, RNA-Seq revealed 1,040 genes expressed differentially in the magnum and 595 genes in the uterus. By combining GO enrichment and KEGG pathway analysis, it served to show that gene activities of the magnum and uterus in prelaying chickens were more likely to concentrate on growth and development, and after egg-laying, they were mainly inclined to enhance the substances transmembrane transport and secretion activities. We further characterized 1579 new genes, while only 803 of them were functionally annotated. A complex mixture of proteins related to defense was measured in this study. A subset of avian ß-defensins (AvBDs) and ovodefensins (OvoDs), that is, AvBD12, AvBD11, AvBD10, OvoDA1, OvoDB1, OvoDA2, OvoDA3, and OvoDBß, was detected to express in the magnum of laying hens at high levels. CONCLUSION: Collectively, the identification and functional analysis of these differentially expressed genes (DEGs), as well as specific expression of avian defensins, may contribute to understand the development and defense mechanisms of oviduct and eggs.

8.
Front Cell Neurosci ; 13: 108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949031

RESUMO

Ascorbic acid (AA) is an essential micronutrient that has been safely used in the clinic for many years. The present study indicates that AA has an unexpected function in facilitating nerve regeneration. Using a mouse model of sciatic nerve crush injury, we found that AA can significantly accelerate axonal regrowth in the early stage [3 days post-injury (dpi)], a finding that was revealed by immunostaining and Western blotting for antibodies against GAP-43 and SCG10. On day 28 post-injury, histomorphometric assessments demonstrated that AA treatment increased the density, size, and remyelination of regenerated axons in the injured nerve and alleviated myoatrophy in the gastrocnemius. Moreover, the results from various behavioral tests and electrophysiological assays revealed that nerve injury-derived functional defects in motor and sensory behavior as well as in nerve conduction were significantly attenuated by treatment with AA. The potential mechanisms of AA in nerve regeneration were further explored by investigating the effects of AA on three types of cells involved in this process [neurons, Schwann cells (SCs) and macrophages] through a series of experiments. Overall, the data illustrated that AA treatment in cultured dorsal root ganglionic neurons resulted in increased neurite growth and lower expression of RhoA, which is an important inhibitory factor in neural regeneration. In SCs, proliferation, phagocytosis, and neurotrophin expression were all enhanced by AA. Meanwhile, AA treatment also improved proliferation, migration, phagocytosis, and anti-inflammatory polarization in macrophages. In conclusion, this study demonstrated that treatment with AA can promote the morphological and functional recovery of injured peripheral nerves and that this effect is potentially due to AA's bioeffects on neurons, SCs and macrophages, three of most important types of cells involved in nerve injury and regeneration.

9.
Immunobiology ; 224(3): 339-346, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30975435

RESUMO

A deficiency of complement factor H may lead to excessive consumption of C3 and an increase in C3b deposition, which are important pathological characteristics of lupus nephritis. Complement factor H-related proteins (CFHRs), comprising CFHR1 to CFHR5 (CFHR1-5), are members of the wider factor H/CFHR family. Their role in lupus nephritis remains unclear. In this study, we compared circulating levels of CFHR1-5 in 152 patients diagnosed with lupus nephritis and 20 unrelated healthy individuals to explore the relationship between the expression of CFHR1-5 and development of the disease. We found that plasma levels of CFHR3 and CFHR5 were higher in patients with lupus nephritis than in healthy individuals; also, CFHR3 and CFHR5 concentrations increased with increasing systemic lupus erythematosus disease activity index (SLEDAI) values (P < 0.05). Pearson's and Spearman's correlation test results confirmed that plasma CFHR3 and CFHR5 levels in lupus nephritis patients were positively correlated with proteinuria and levels of creatinine (Cr) and anti-dsDNA (correlation coefficients = 0.491-0.717, P < 0.05), while they were negatively correlated with plasma C3 levels and eGFR [correlation coefficients = -(0.706-0.788), P < 0.05]. Receiver operating characteristic (ROC) curve analysis results confirmed that plasma CFHR3 and CFHR5 levels were predictive of SLEDAI values and disease end points (area under the curve = 0.664-0.884, P < 0.05), with patients with both high CFHR3 and high CFHR5 exhibiting the shortest progression-free survival. Thus, both CFHR3 and CFHR5 are of prognostic value in lupus nephritis status.

10.
Eur J Pharmacol ; 845: 91-98, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30287151

RESUMO

Vitamin D has been suggested to harbor multiple biological activities, among them the potential of vitamin D in the protection of diabetic nephropathy (DN) has attracted special attention. Both animal studies and clinical trials have documented an inverse correlation between low vitamin D levels and DN risk, and supplementation with vitamin D or its active derivatives has been demonstrated to improve endothelial cell injury, reduce proteinuria, attenuate renal fibrosis, and resultantly retard DN progression. Vitamin D exerts its pharmacological effects primarily via vitamin D receptor, whose activation inhibits the renin-angiotensin system, a key culprit for DN under hyperglycemia. The anti-DN benefit of vitamin D can be enhanced when administrated in combination with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. Mechanistic studies reveal that pathways relevant to inflammation participate in the pathogenesis of DN, however, consumption of vitamin D-related products negatively regulates inflammatory response at multiple levels, indicated by inhibiting macrophage infiltration, nuclear factor-kappa B (NF-κB) activation, and production of such inflammatory mediators as transforming growth factor-ß(TGF-ß), monocyte chemoattractant protein 1(MCP-1), and regulated upon activation normal T cell expressed and secreted protein(RANTES). The robust anti-inflammatory property of vitamin D-related products allows them with a promising renoprotective therapeutic option for DN. This review summarizes new advances in our understanding of vitamin D-related products in the DN management.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Receptores de Calcitriol/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Vitamina D/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Quimiocina CCL2/efeitos dos fármacos , Quimiocina CCL5/efeitos dos fármacos , Quimioterapia Combinada , Células Endoteliais/patologia , Humanos , NF-kappa B/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Fator de Crescimento Transformador beta/efeitos dos fármacos , Vitamina D/farmacologia
11.
Front Cell Neurosci ; 12: 437, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30515082

RESUMO

Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway.

12.
Clin Chim Acta ; 486: 275-281, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30125535

RESUMO

OBJECTIVE: A key step in the evaluation of the accuracy of blood glucose monitoring systems (BGMS) is using a comparator method aligned to a high order definitive reference method. We describe how we achieved traceability to an isotope dilution liquid chromatography mass spectrometry (ID-LCMS) method. We used ID-LCMS to evaluate the accuracy and specificity of two hospital BGMS used in China. METHOD: ID-LCMS was used to verify the calibration alignment of the laboratory plasma hexokinase reference method using NIST standard reference material and clinical samples. The ID-LCMS aligned hexokinase method was used to evaluate the clinical accuracy of two BGMS in hospitalized patients. System accuracy was evaluated using Chinese consensus guidelines. BGMS accuracy was also assessed with interference factors known to be present in critically ill patients' blood. RESULTS: The laboratory plasma hexokinase reference method was shown to calibrate closely with ID-LCMS. Two BGMS demonstrated good correlation with this reference method. Only one BGMS met the Chinese guidelines. The interference factors didn't influence this BGMS but adversely affected the clinical accuracy of the other. CONCLUSIONS: We advocate that our IDMS calibration alignment approach for ensuring the accuracy of the glucose reference method should be adopted in evaluations assessing the accuracy of blood glucose monitoring systems.


Assuntos
Automonitorização da Glicemia/normas , Glicemia/análise , Calibragem , Cromatografia Líquida/normas , Hexoquinase/sangue , Hexoquinase/metabolismo , Humanos , Espectrometria de Massas/normas , Técnica de Diluição de Radioisótopos/normas , Padrões de Referência
13.
J Ethnopharmacol ; 225: 202-210, 2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-29981847

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Physalis alkekengi (PA) is used in traditional medicine to treat diabetes. However, the anti-diabetic effects and constituents of the fruit and aerial parts of this plant have not been studied extensively. AIM OF THE STUDY: The purpose of this study was to investigate the antidiabetic potential of Physalis alkekengi and identify its chemical constituents. MATERIALS AND METHODS: In the present study, the in vitro glucose uptake capacity was tested using the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay in HepG2 cells. Secondly, the anti-diabetes effects of the ethyl acetate extracts of the aerial parts/fruit (EAP/EAF) of P. alkekengi were evaluated in high-fat diet-fed and streptozotocin-induced diabetic rats (seven groups, n = 7) daily at doses of 300 and 600 mg/kg for 28 days. Fasting blood glucose (FBG) was measured with a glucometer and the levels of total cholesterol (TC), triglyceride (TG), glycated serum protein (GSP), and fasting insulin (FINS) were measured by ELISA. Furthermore, insulin sensitivity index (ISI) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated based on FBG and FINS. Changes in blood glucose concentration were assessed after an oral glucose challenge in diabetic rats treated with EAF and EAP extracts. In all assays, rosiglitazone, a current antidiabetic drug and insulin sensitizer, was also tested. Finally, the compounds in EAP were identified by HPLC-ESI-QTOF-MS analysis. RESULTS: EAP increased the uptake of 2-NBDG, a measure of direct glucose uptake, in HepG2 cells. Next, in diabetic rats treated with P. alkegenki extracts for 28 days, the levels of FBG, TC, TG and GSP and were lowered effectively, while FINS was increased significantly. EAP/EAF enhanced insulin sensitivity significantly as measured by ISI and HOMA-IR along with oral glucose tolerance test analysis. The EAP generally exerted the greatest effects. Lastly, a HPLC-ESI-Q-TOF-MS analysis identified 50 compounds, including 26 physalins, 10 flavonoids, and 9 phenolic acids, with 21 compounds found for the first time in P. alkekengi. CONCLUSIONS: The results support the merit of P. alkekengi as an antidiabetic herbal medicine or dietary supplement.


Assuntos
Hipoglicemiantes/uso terapêutico , Physalis , Extratos Vegetais/uso terapêutico , Acetatos/química , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Glucose/metabolismo , Teste de Tolerância a Glucose , Células Hep G2 , Humanos , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Insulina/sangue , Resistência à Insulina , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Solventes/química , Espectrometria de Massas por Ionização por Electrospray
14.
Clin Lab ; 64(6): 1037-1040, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945322

RESUMO

BACKGROUND: To study the clinical effect of low molecular heparin on unexplained recurrent spontaneous abortion (URSA). METHODS: A total of 120 URSA patients were collected in our hospital from October 2015 to September 2017. They were divided into two groups: control group (n = 60) and observation group (n = 60). The patients in the control group were administered with progesterone and human chorionic gonadotropin, and the observation group with low molecular heparin. Pregnancy outcomes, incidence of complications in pregnancy and adverse drug reactions were compared in the two groups. RESULTS: The pregnancy success rate of patients in the observation group (90.00%) is higher than that in the control group (68.33%) (p < 0.05). The incidence of complications in pregnancy in the observation group (90.00%) is lower than those in the control group (68.33%) (p < 0.05). The incidence of adverse drug reactions between the patients in the observation group (20.00%) and those in the control group (23.33%) showed no significant difference (p > 0.05). CONCLUSIONS: Low molecular heparin treatment can improve pregnancy success rate and reduce the incidence of complications in the URSA patients. Low molecular heparin is characterized by safety and reliability and has potential for application in clinic.


Assuntos
Aborto Habitual/prevenção & controle , Aborto Espontâneo/prevenção & controle , Heparina de Baixo Peso Molecular/administração & dosagem , Resultado da Gravidez , Adulto , Gonadotropina Coriônica/administração & dosagem , Feminino , Humanos , Gravidez , Progesterona/administração & dosagem , Resultado do Tratamento
15.
Biomed Res Int ; 2018: 3452748, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682535

RESUMO

Objective: To explore the effect of microRNA-132 of heart failure and provide theoretical guidance for clinical treatment of heart failure (HF). Methods: Peripheral blood was collected from HF patients. RT-qPCR was used to determine microRNA-132 expression. Mouse models of heart failure were established. Color Doppler ultrasound was utilized to measure the changes of cardiac function. HE and Masson staining were applied to observe pathological changes of the myocardium. After H9C2 cells were transfected with microRNA-132, MTT assay was employed to detect the stability of H9C2 cells. ELISA was used to measure the levels of oxidative stress factors. Western blot assay and RT-qPCR were utilized to determine the expression of Bax, Bcl-2, TGF-ß1, and smad3. Results: MicroRNA-132 expression was downregulated in HF patients' blood. After establishing mouse models of HF, cardiac function obviously decreased. HE staining revealed the obvious edema and hypertrophy of cardiomyocytes. Masson staining demonstrated that cardiomyocytes were markedly fibrotic. After microRNA-132 transfection and H9C2 cell apoptosis induced by H2O2, antioxidant stress and antiapoptotic ability of the H9C2 cells obviously increased. TGF-ß1 and smad3 expression remarkably diminished. Conclusion: Overexpression of microRNA-132 dramatically increased the antioxidant stress and antiapoptotic ability of H9C2 cells and decreased the expression of TGF-ß1 and smad3.


Assuntos
Apoptose/genética , Insuficiência Cardíaca/genética , MicroRNAs/genética , Estresse Oxidativo/genética , Animais , Antioxidantes/metabolismo , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética , Proteína X Associada a bcl-2/genética
16.
Fitoterapia ; 127: 129-137, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29447981

RESUMO

The aims of the present study were to assess the anti-diabetic effects of Physalis alkekengi L. (PA) in 3T3-L1 pre-adipocyte cells and HepG2-GFP-CYP2E1 (E47) cells and in a pre-diabetic rat model, as well as to identify the active chemical constituents. The in vitro results showed that PA has a strong anti-diabetic capacity to relieve oxidative stress and inhibit α-glucosidase activity. Mechanistic analysis also showed that ethyl acetate extracts of aerial parts and fruit of PA (PAG-EA and PAF-EA) enhanced glucose transporter 4 expression and function as well as enhanced insulin sensitivity by inhibiting the expression of cytochrome P450-2E1 (CYP2E1) mRNA and protein. In vivo, PAG-EA and PAF-EA significantly decreased the levels of fasting blood glucose and fasting insulin, as well as total cholesterol and triglyceride, in the pre-diabetic rats. The results from insulin sensitivity index and homeostasis model assessment-insulin resistance index along with an oral glucose tolerance test also showed that PAG-EA and PAF-EA could significantly enhance the insulin sensitivity, which confirmed the in vitro findings. Moreover, HPLC-ESI-QTOF-MS analysis identified flavonoids, physalins and phenolic acids as the main plant constituents. Our findings support the ethnopharmacological use of PA fruit, along with its aerial parts, as a strong anti-diabetic agent. The EA fraction, especially the constituent polyphenols and flavonoids, may have a good potential to treat diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Physalis/química , Polifenóis/farmacologia , Células 3T3-L1 , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/isolamento & purificação , Frutas/química , Teste de Tolerância a Glucose , Células Hep G2 , Humanos , Hipoglicemiantes/isolamento & purificação , Resistência à Insulina , Masculino , Camundongos , Estresse Oxidativo , Componentes Aéreos da Planta/química , Polifenóis/isolamento & purificação , Ratos , Ratos Sprague-Dawley
17.
Genes (Basel) ; 9(1)2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29300342

RESUMO

There is increasing evidence for the contribution of synuclein alpha (SNCA) to the etiology of neurological disorders, such as Parkinson's disease (PD). However, little is known about the detailed role of SNCA in human cancers, especially lung cancers. Here, we evaluated the effects of SNCA on the occurrence and prognosis of lung adenocarcinoma (ADC). Comprehensive bioinformatics analyses of data obtained from the Oncomine platform, the human protein atlas (HPA) project and the cancer cell line encyclopedia (CCLE) demonstrated that SNCA expression was significantly reduced in both ADC tissues and cancer cells. The results of relevant clinical studies indicated that down-regulation of SNCA was statistically correlated with shorter overall survival time and post-progression survival time. Through analysis of datasets obtained from the Gene Expression Omnibus database, significant low levels of SNCA were identified in cisplatin-resistant ADC cells. Moreover, small interfering RNA (siRNA)-mediated knockdown of protein tyrosine kinase 7 (PTK7) elevated the expression of SNCA in the ADC cell lines H1299 and H2009. Our work demonstrates that low levels of SNCA are specifically found in ADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determination of the role of SNCA in ADC biology would give us some insightful information for further investigations.

18.
J Colloid Interface Sci ; 505: 870-883, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28672266

RESUMO

Ti-modified Co3O4 catalysts with various Co/Ti ratios were synthesized using the co-precipitation method and were used in catalytic oxidation of dibromomethane (CH2Br2), which was selected as the model molecule for brominated volatile organic compounds (BVOCs). Addition of Ti distorted the crystal structure and led to the formation of a Co-O-Ti solid solution. Co4Ti1 (Co/Ti molar ratio was 4) achieved higher catalytic activity with a T90 (the temperature needed for 90% conversion) of approximately 245°C for CH2Br2 oxidation and higher selectivity to CO2 at a low temperature than the other investigated catalysts. In addition, Co4Ti1 was stable for at least 30h at 500ppm CH2Br2, 0 or 2vol% H2O, 0 or 500ppm p-xylene (PX), and 10% O2 at a gas hourly space velocity of 60,000h-1. The final products were COx, Br2, and HBr, without the formation of other Br-containing organic byproducts. The high catalytic activity was attributed to the high Co3+/Co2+ ratio and high surface acidity. Additionally, the synergistic effect of Co and Ti made it superior for CH2Br2 oxidation. Furthermore, based on the analysis of products and in situ DRIFTs studies, a receivable reaction mechanism for CH2Br2 oxidation over Ti-modified Co3O4 catalysts was proposed.

19.
IEEE Trans Neural Netw Learn Syst ; 28(8): 1889-1901, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27187973

RESUMO

The memristor has been extensively studied in electrical engineering and biological sciences as a means to compactly implement the synaptic function in neural networks. The cellular neural network (CNN) is one of the most implementable artificial neural network models and capable of massively parallel analog processing. In this paper, a novel memristive multilayer CNN (Mm-CNN) model is presented along with its performance analysis and applications. In this new CNN design, the memristor crossbar circuit acts as the synapse, which realizes one signed synaptic weight with a pair of memristors and performs the synaptic weighting compactly and linearly. Moreover, the complex weighted summation is executed in an efficient way with a proper design of Mm-CNN cell circuits. The proposed Mm-CNN has several merits, such as compactness, nonvolatility, versatility, and programmability of synaptic weights. Its performance in several image processing applications is illustrated through simulations.

20.
Sci Rep ; 6: 34761, 2016 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-27713472

RESUMO

In this work, the underlying micro-damage mechanisms of randomly oriented short fibre-reinforced composites were revealed based on real internal microstructural characteristics obtained by high-resolution (0.7 µm/pixel) synchrotron radiation X-ray computed tomography (SR-CT). The special 'pore dominant micro-damage processes' were directly observed through SR-CT three-dimensional reconstructed images, which were different from the well-known 'fibre breakage dominant failure mode'. The mechanisms of pore formation and pore evolution were further investigated on the basis of the microstructural parameters extracted from the SR-CT results. On one hand, the pore formation mechanism caused by shear stress concentration was proposed by combining the shear-lag model with the microstructural parameters obtained from the experiment, including the fibre length and orientation angle. On the other hand, the 'fibre-end aggregation-induced pore connection' mode of crack initiation was proposed through a composites model, which considered the parameters of real internal microstructure, including the critical value of the distance between neighbouring fibre ends and the number of neighbouring fibre ends. The study indicated that the shear stress concentration was significant in the region with a large number of neighbouring fibre ends, thus causing pore connection and crack initiation.

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