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1.
Toxicol In Vitro ; 62: 104698, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669364

RESUMO

Both PM2.5 and respiratory viruses are part of the atmospheric constituents. Respiratory viruses are often associated with PM2.5 exposure, but the mechanism of toxicity remains to be explored. The vitro models that adequately reproduce healthy cells or diseased cells exposing to PM2.5 and infecting VSV can provide a useful tool for studying innate immune mechanisms and investigating new therapeutic focus. In the environment of PM2.5, an infection model in which VSV infected A549 cells was established, that mimics the state in which the antiviral innate immune pathways are activated after the respiratory system is infected with RNA viruses. Subsequently, the model was exposed to PM2.5 for 24 h. PM2.5 could be ingested by A549 cells and synergize with VSV to inhibit cell viability and promote apoptosis. The expression of VSV-G were more abundant after VSV-infected A549 cells were exposed to PM2.5. Furthermore, PM2.5 inhibits VSV-induced IFN-ß expression in A549 cells. ISG15, CCL-5, and CXCL-10 had the same expression tendency with IFN-ß mRNA, consistently. Interestingly, when MG132 was applied, the expression of p-IRF-3 and IFN-ß proteins reduced by PM2.5 were refreshed. Conversely, the expression of VSV-G proteins were decreased. PM2.5 could degrade p-IRF-3 proteins by ubiquitination pathway to inhibit VSV-induced IFN-ß expression in A549 cells. Therefore, replication of the VSV viruses was promoted.

2.
Sci Total Environ ; : 134833, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796276

RESUMO

The spatial variation of chlorophyll a in the Southern Ocean (SO) was of great significance. Sea surface chlorophyll a concentrations was measured by Ferry Box monitoring system on the Chinese polar research vessel Xue Long, which circumnavigated the Antarctic continent in a clockwise direction during the austral summer 2013-2014 (November 2013-April 2014). The concentrations of chlorophyll a indicated a relatively uniform distribution of 0.049-11.647 mg m-3 (mean 0. 869 mg m-3, n = 152,751). The highest chlorophyll a concentrations (mean 1.847 mg m-3) was found in the Ross sea (RS). In addition, six high-chlorophyll a hot spots were recognized. Analysis revealed that phytoplankton bloom could be controlled by multiple factors in different regions, and the chlorophyll a bloom is attributed to the combined effect of surface and subsurface processes such as, continental shelf, sea ice melting, Circumpolar Deep Water (CDW) upwelling, suitabletemperature, and nutrient injection from subsurface to the surface. The topographic effects, sea ice melting and CDW upwelling may play a major role in controlling primary productivity in the SO. Among of all, CDW upwelling may be the most important role improving primary productivity. This study presented the phytoplankton distribution patterns and the relation with potential growth-controlling factors in the SO, which will provide more insight in the mechanisms that control global warming to reduce global CO2 the atmosphere into the ocean interior.

3.
Curr Alzheimer Res ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797758

RESUMO

BACKGROUND: Neuroinflammation and oxidative stress have important effects on cognitive functions in the pathophysiological process of Alzheimer's disease (AD). In the current study, we determined the effects of Ampelopsin (AMP) on the levels of proinflammatory cytokines (PICs, IL-1ß, IL-6 and TNF-α), and products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, a product of oxidative stress); and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a key biomarker of protein oxidation) in the hippocampus using a rat model of AD. METHODS: ELISA was used to examine PICs and products of oxidative stress; and western blot analysis was used to examine protein expression of NADPH oxidase (NOXs). The Spatial working memory tests and Morris water maze were used to assess cognitive functions. RESULTS: We observed amplification of IL-1ß, IL-6 and TNF-α as well as 8-iso PGF2α and 8-OHdG in the hippocampus of AD rats. Systemic administration of AMP attenuated upregulation of PICs and products of oxidative stress. AMP also inhibited NOX4 in the hippocampus of AD rats. Notably, AMP largely recovered the impaired learning performance in AD rat and this was linked to signal pathways of PIC and oxidative stress. CONCLUSION: We showed the significant role of AMP in improving the memory impairment in AD rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress suggesting that AMP may present prospects in preventing and/or alleviating development of the impaired cognitive functions in AD as a complementary alternative intervention.

4.
Am J Emerg Med ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31785983

RESUMO

AIM: We sought to evaluate whether the quality of coordination between physicians transferring comatose cardiac arrest survivors to a high-volume cardiac arrest center for targeted temperature management (TTM) was associated with timeliness of care. METHODS: We conducted a retrospective analysis of inter-facility transfers to Vanderbilt University Medical Center for TTM between October 2016 and October 2018. We examined the relationship between Relational Coordination (RC) - a measure of communication and relationship quality - during phone conversations between transferring physicians and time-to-acceptance. RESULTS: We identified 18 patients meeting criteria. TTM was initiated or continued in 72%, and in-hospital mortality was 75%. Median time-to-acceptance was 2.77 (interquartile range [IQR] 2.0, 4.1) minutes, and duration of calls was 3.95 (IQR 2.7, 5.2) minutes. Interrater reliability for overall RC was high (rho = 0.87). The correlation between RC and the time-to-acceptance was significant in univariate analyses (adjusted relative risk = 0.96, 95%CI 0.93, 1.0, p = 0.05). Secondary analyses did not find a significant relationship between RC and timeliness measures. CONCLUSION: In this sample of patients transferred for TTM, we found that RC as a measure of care coordination, was reliable. Higher quality care coordination for cardiac arrest survivors was associated with faster physician acceptance. Future work using a larger cohort should explore if higher RC among a broader set of stakeholders (physicians, EMS, families, etc.) is associated with timeliness measures after adjusting for other factors, to better understand how the quality of care coordination impacts timeliness of care and patient outcomes.

5.
Parasitol Res ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754855

RESUMO

A new Caryospora-like isolate is described from a magpie-lark (Grallina cyanoleuca) in Western Australia. Sporulated oocysts of the Caryospora-like isolate (n = 35) are subspherical with a shape index of 1.13 ((21.5 (19.7-23.6) × 19.0 (18.1-19.8) µm). The bilayered oocyst wall is smooth. Micropyle, polar granule and oocyst residuum are absent. The sporocyst is ellipsoidal, 18.9 (17.2-20.8) × 12.3 (11.9-12.8) µm, with a shape index (length/width) of 1.54. The sporocyst wall is bilayered. Stieda and substieda bodies are present, the Stieda body is small and flattened and the substieda is trapezoidal. Sporocyst with eight sporozoites arranged head to tail. The sporozoites are vermiform, 18.9 (17.2-20.8) × 12.3 (11.9-12.8) µm and have striations at the anterior end. Each sporozoite has both anterior and posterior refractile bodies. A sporocyst residuum is present. Molecular characterization of the isolated Caryospora-like oocysts was conducted at the 18S ribosomal RNA and the mitochondrial cytochrome oxidase (COI) loci. At the 18S rRNA locus, the Caryospora-like isolate exhibited 88.8% to 96.5% similarity with other Caryospora spp. from different hosts. At the COI locus, it showed 91.5% similarity to Caryospora cf. bigenetica JB-2013 (KF859856) from the rattlesnake, Sistrurus catenatus.

6.
Bioorg Med Chem Lett ; 29(24): 126773, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31718863

RESUMO

Early and accurate diagnosis of influenza viruses can decrease its harmful impact. Here, we have synthesized fluorescent sialic acid derivatives that are cleaved by influenza neuraminidases (NAs) and not by Streptococcus pneumoniae that also inhabits the human olfactory. We have also attempted to develop assays that could differentiate between influenza virus and S. pneumoniae by taking advantage of the structural differences between NAs from these pathogens.

7.
Biomed Res Int ; 2019: 9542054, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781656

RESUMO

Serum calcium has been reported to be a predictor of short-term prognosis; however, evidence regarding its association with midterm mortality is scarce. We investigated the association between serum calcium levels at admission and midterm mortality in a retrospective cohort of 2594 consecutive patients with acute coronary syndrome (ACS) who presented to the First Affiliated Hospital of Harbin Medical University from November 2014 to December 2016. Patients were assigned to 4 groups according to the quartiles of serum calcium levels (Ca-Q1-4) and were followed longitudinally for the time to all-cause death. During a median follow-up period of 21.8 months (17.5∼29.5, IQR), 124 patients died (4.8%) of all causes. Kaplan-Meier curves showed that the incidence of midterm mortality differed significantly (log-rank P=0.038) among the quartiles of serum calcium levels at admission. After adjustment for the confounders that were significant in the univariate analysis, the hazard ratios for the lowest quartile of serum calcium was 1.86 (95% CI, 1.05-3.31; P=0.033), compared with the third quartile (reference group). A multiple restricted cubic spline regression model suggested a reverse J-shaped association between serum calcium levels and midterm mortality, and the lowest risk of mortality was associated with approximately 2.32 mmol/l of serum calcium. In conclusion, the serum calcium level is an independent predictor of all-cause midterm mortality among ACS patients. Patients with abnormal serum calcium levels at admission need more targeted treatments.

8.
BMC Vet Res ; 15(1): 408, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711494

RESUMO

BACKGROUND: Akabane disease (AD), a barrier to international trade for endemic areas with far economic impact on the countries, is caused by Akabane virus (AKAV). Commercial enzyme-linked immunosorbent assay (ELISA) is a commonly used diagnostic technique for AKAV infection, including the IDEXX and IDVET ELISA kits. However, the comparative evaluation of the IDEXX and IDVET ELISA kits has not been published. The object of this study was to evaluate the test performance of the two commercial ELISA kits in detecting serum anti-AKAV antibodies in cattle. RESULTS: With virus neutralization test (VNT) as the "relative gold standard", the diagnostic sensitivity (DSe) was 80.39% (123/153) and 93.46% (143/153) for the IDEXX and IDVET ELISA kit, when suspect samples were included. The diagnostic specificity (DSp) for the IDEXX and IDVET ELISA kit was 93.48% (502/537) and 82.31% (442/537), respectively. CONCLUSION: Both of the tested ELISA kits could be applied to detect antibodies against AKAV in cattle serum. The IDVET ELISA kit had a higher DSe. The IDEXX ELISA kit possessed the higher DSp. These results have important implications if the kits are used to screen herds or individual cattle in surveillance programs, or at border crossings for import-export inspection and quarantine.

9.
J Inorg Biochem ; 202: 110857, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669695

RESUMO

Thirteen novel palladium(II) complexes of the general formula [Pd(bipy)(O,O'-dkt)](PF6), (where bipy is 2,2'-bipyridine and O,O'-dkt is ß-diketonate ligand hispolon or its derivative) have been prepared through a metal-ligand coordination method that involves spontaneous formation of the corresponding diketonate scaffold. The obtained palladium(II) complexes have been characterized by NMR spectroscopy, ESI-mass spectrometry as well as elemental analysis. The cytotoxicity analysis indicates that most of the obtained palladium(II) complexes show promising growth inhibition in three human cancer cell lines. Flow cytometry analysis shows complex 3e could promote intracellular reactive oxygen species (ROS) accumulation and lead cancer cell death. And the suppression of ROS accumulation and the rescue of cell viability in HeLa cells by N-acetyl-L-cysteine (NAC) suggest the possible link between the increase in ROS generation and cytotoxicity of complex 3e. Flow cytometry analysis also reveal that complex 3e cause cell cycle arrest in the G2/M phase and collapse of the mitochondrial membrane potential, promote the generation of ROS and lead to tumor cell apoptosis. The interactions of complex 3e with calf thymus DNA (CT-DNA) have been evaluated by UV-Vis spectroscopy, fluorescence quenching experiments and viscosity measurements, which reveal that the complex interact with CT-DNA through minor groove binding and/or electrostatic interactions. Further, the results of fluorescence titration and site marker competitive experiment on bovine serum albumin (BSA) suggest that complex 3e can quench the fluorescence of BSA via a static quenching process and bind to BSA in Sudlow's site II.

10.
J Transl Med ; 17(1): 378, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730006

RESUMO

BACKGROUND: Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet. RESULTS: We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo. CONCLUSIONS: Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.

11.
Viruses ; 11(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717338

RESUMO

RNA viruses are highly successful pathogens and are the causative agents for many important diseases. To fully understand the replication of these viruses it is necessary to address the roles of both positive-strand RNA ((+)RNA) and negative-strand RNA ((-)RNA), and their interplay with viral and host proteins. Here we used branched DNA (bDNA) fluorescence in situ hybridization (FISH) to stain both the abundant (+)RNA and the far less abundant (-)RNA in both hepatitis C virus (HCV)- and Zika virus-infected cells, and combined these analyses with visualization of viral proteins through confocal imaging. We were able to phenotypically examine HCV-infected cells in the presence of uninfected cells and revealed the effect of direct-acting antivirals on HCV (+)RNA, (-)RNA, and protein, within hours of commencing treatment. Herein, we demonstrate that bDNA FISH is a powerful tool for the study of RNA viruses that can provide insights into drug efficacy and mechanism of action.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1360-1366, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607284

RESUMO

OBJECTIVE: To summarize the clinical characteristics of patients with acute myeloid leukemia-type M2 (AML-M2) and analyze the factors affecting the prognosis. METHODS: One hundred eighty-eight AML-M2 patients were retrospectively analyzed for the following parameters including peripheral blood, immune phenotypes, fusion genes and cytogenetics to explore their significance for the overall survival (OS) and progression-free survival (PFS). The prognostic factors were also analyzed. RESULTS: Among 188 patients with AML-M2, the chromosomal abnormality with t (8;21), normal chromosome and other abnormalities accounted for 37% (70/188), 41% (77/188) and 22% (41/188), respectively. For the immunopheno typing of M2 patients, the hematopoietic progenitor cell differentiation antigen CD117 (96.1%) were mainly expressed, CD34 (81.6%) and HLA-DR (55.9%), and myeloid-associated antigen of CD13 (90.5%) and CD33 (89.4%) were also highly expressed. There were lymphoid-associated antigens expressed in some patients, among which the positive expression rate of CD19 was highest (29.6%), and the next was CD7 (28.5%). The most common accompanied mutations was FLT3 mutation (30.2%). The univariate analysis showed that the patients at age<50 years old, without extramedullary infiltration, with positive expression of CD19, NPM-1 (-), CEBPA double mutation(+), and HSCT were significant superior in OS and PFS (P<0.05); the multivariate analysis showed that the patient at age<50 years old, without extramedullary infiltration, with positive expression of CD19 and CEBPA double mutation (+) were significant superior in OS and PFS (P<0.05). The analysis indicated that the Karytypes affected only OS (P<0.05), while the NPM-1 gene mutation positive affected only PFS (P<0.05). The univarate analysis of factors affecting the survival in 70 AML-M2 patients with t (8;21) abnormatity showed that the C-KIT gene mutation was a poor factor for OS and PFS. CONCLUSION: The clinical characteristics are different between M2 patients with different karyotype, and prognostic analysis shows that the karytypes have an impact on overall survival; age, extramedullary infiltration, CD19 expression and CEBPA double mutation are also the main factors impacting the prognosis of patients.


Assuntos
Leucemia Mieloide Aguda , Antígenos HLA-DR , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos
13.
AAPS PharmSciTech ; 20(8): 309, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520191

RESUMO

A synthetic, dispersible magnesium aminoclay (MgAC) was synthesized in the present study. Besides, structural and spectroscopic detections were conducted to investigate the MgAC nanoclay. With a poor aqueous solubility, methotrexate (MTX) has been applied as a valid antitumor agent in recent years. In our research, an unobtrusive sol-gel process was carried out to manufacture the MgAC-MTX nanohybrids through entrapment of MTX over MgAC in situ. The final product was capable of desquamating and thus dispersed in water, equably. In comparison with rough MTX, the MgAC-MTX nanocomposite with a preferable treatment efficacy against MCF-7 cells was mainly attributed to the preeminent enhanced aqueous solubility, controlled release and the increased cellular uptake capacity. Moreover, with excellent anticancer function and hypotoxicity as vindicated in vivo, the MgAC-MTX nanohybrid was supposed to own the potency in the application of malignant tumors cure as a valid nanomedicine. It turned out that, by virtue of its high bioavailability, the MgAC-MTX nanohybrids with high bioavailability is deserving of further study for the treatment of cancers.

14.
Neurotoxicology ; 75: 221-232, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31562916

RESUMO

This study aimed to explore effects and mechanisms of 004 (IMM-H004), a novel coumarin derivative, in OKA (okadaic acid)-induced AD (Alzheimer's disease)-like model. In vitro, MTT, LDH, and Annexin V/FITC flow cytometry assay were used to test cell survival. In vivo, OKA microinjection was conducted to simulate AD-like neuropathology. Morris water maze and Nissl staining were used to detect spatial memory function and neuronal damage respectively. Western blot and immunohistochemistry were used to study the mechanisms of 004 in Tau pathology. The results showed that 004 reduced cell death and increased survival in PC12 cells, and decreased neuronal injury in the hippocampus in rats. 004 improved learning and memory functions in OKA-treated rats. The mechanistic studies indicated that 004 inhibited phosphorylation of Tau protein by down-regulating the activity of protein kinases CDK5 and GSK3ß and increasing PP2A activity. Overall, 004 improved spatial memory impairments and neuron cells injury induced by OKA; on the other hand, 004 inhibited Tau hyperphosphorylation by regulating CDK5, GSK3ß and PP2A.

15.
Org Lett ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433660

RESUMO

Total synthesis of (±)-cochlearol A was accomplished, which features a cis 6/6 B/D ring synthesis. A TMSOTf-promoted lactonization of tert-butoxy ketoester produced the desired lactone with quaternary carbon. The cis configuration of the B/E ring is essential for regioselective B/D ring formation. Finally, simple deprotections and transformations gave cochlearol A in 16 steps from known ethyl 4-tert-butoxyacetoacetate.

16.
J Am Heart Assoc ; 8(15): e011146, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31364446

RESUMO

Background Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-ε4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-ε4 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73±7 years, 42% female) underwent echocardiography to determine cardiac output (L/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and ε4 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-ε4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output×APOE-ε4 status interaction and again stratified by ε4 carrier status. Cardiac output×APOE-ε4 status related to naming (ß=0.91, P=0.0009), category fluency (ß=1.2, P=0.01), information processing speed (ß=-5.4, P=0.001), visuospatial skill (ß=0.85, P=0.003), and executive function performances (ß=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-ε4 carriers. Conclusions APOE-ε4 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the ε4 allele. These findings add to increasing evidence that APOE-ε4 carrier status has important implications for associations between vascular and brain health in aging adults.

17.
Acta Biomater ; 99: 350-362, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31449929

RESUMO

Dry eye syndrome is a common eye disease that affects many people worldwide. It is usually treated with eye drops, which has low bioavailability owing to rapid clearance from the ocular surface and leads to poor patient compliance and side effects. For the purpose of improving the therapeutic efficacy, nanostructured lipid carrier (NLC)-loaded dexamethasone (DEX) was prepared and functionalized with (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS). As APBA has a boronic acid group, it can form a high-affinity complex with sialic acids present in the ocular mucin, which contributes to extension of corneal retention time and improvement of drug delivery. Compared with eye drops, Rhodamine B (RhB)-labeled APBA-ChS-NLC could significantly prolong the residence time on the corneal surface. Moreover, the DEX-APBA-ChS-NLC showed no irritation to the rabbit eye as indicated in irritation studies and histological images. The pharmacodynamics study indicated that DEX-APBA-ChS-NLC could relieve symptoms of dry eye disease in rabbits. These results demonstrated that the developed mucoadhesive drug carrier could improve the delivery of drugs and have promising potential to treat anterior eye diseases. STATEMENT OF SIGNIFICANCE: In this research, (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS)-based nanostructured lipid carriers (NLCs) including dexamethasone (DEX) were designed and constructed. APBA-ChS, which is present on the surface of DEX-NLC and contains the boronic acid group, can form complex with sialic acids in the ocular mucin, hence leading to prolonged precorneal retention. This affinity between boronic acid and sialic acids was used to develop a mucoadhesive drug delivery system. The developed mucoadhesive drug carrier demonstrated prolonged retention time and alleviation of dry eye syndrome. APBA-ChS-based NLC may be considered a promising ocular drug delivery system for treating anterior eye diseases.

18.
Curr Alzheimer Res ; 16(6): 473-482, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456514

RESUMO

BACKGROUND: Neuroinflammation has important effects on cognitive functions in the pathophysiological process of Alzheimer's Disease (AD). In the current report, we determined the effects of microRNA-155 (miR-155) on the levels of IL-1ß, IL-6 and TNF-α, and their respective receptors in the hippocampus using a rat model of AD. METHODS: Real-time RT-PCR, ELISA and western blot analysis were used to examine the miR-155, PICs and PIC receptors. The Morris water maze and spatial working memory tests were used to assess cognitive functions. RESULTS: miR-155 was increased in the hippocampus of AD rats, accompanied by amplification of IL-1ß, IL-6 and TNF-α. Intracerebroventricular infusion of miR-155 inhibitor, but not its scramble attenuated the increases of IL-1ß, IL-6 and TNF-α and upregulation of their receptors. MiR-155 inhibitor also attenuated upregulation of apoptotic Caspase-3 in the hippocampus of AD rats. Notably, inhibition of miR- 155 or PIC receptors largely recovered the impaired learning performance in AD rat. CONCLUSION: We showed the critical role of miR-155 in regulating the memory impairment in AD rats likely via engagement of neuroinflammatory mechanisms, suggesting that miR-155 and its signaling molecules may present prospects in preventing and/or improving the development of the impaired cognitive functions in AD.

19.
Cancer Biomark ; 26(2): 183-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403943

RESUMO

BACKGROUND: miR-539 functions as a tumor suppressor in many types of cancer. However, the role of miR-539 in gastric cancer remains unclear. The aim of this study is to investigate the clinical significance and functional role of miR-539 in gastric cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-539 in gastric cancer patients tissues and cells. We analyzed the association between miR-539 expression levels and clinicopathological features, as well as overall survival information with Kaplan-Meier survival curves and Cox regression analysis. The functional role of miR-935 on the proliferation, migration, and invasion was also investigated by using miR-539 mimic or miR-539 inhibitor through CCK-8 assay, Transwell migration and invasion assays. The relationship between miR-539 and RUNX2 was verified by a dual luciferase assay. RESULTS: The expression of miR-539 was decreased in gastric cancer tissues and cell lines. Downregulation of miR-539 was closely associated with differentiation, lymph node metastasis, TNM stage, and poor survival outcome of gastric cancer patients. Furthermore, overexpression of miR-539 inhibited cell proliferation, migration, and invasion of gastric cancer cells. In addition, RUNX2 was a direct target of miR-539. CONCLUSION: Taken together, miR-539 may serve as a tumor suppressor for inhibiting cell proliferation, migration, and invasion by targeting RUNX2. Reduced expression of miR-539 is an independent prognostic factor in gastric cancer and may be a potential prognostic biomarker and miR-539/RUNX2 axis may serve as a potential therapeutic target for the treatment of gastric cancer.

20.
Life Sci ; 234: 116735, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394124

RESUMO

AIMS: The present study was to investigate the protective effects of Zn supplementation in OTA-induced apoptosis of Madin-Darby canine kidney (MDCK) epithelial cells and explore the potential mechanisms. Aiming to provides a new insight into the treatment strategy of OTA-induced nephrotoxicity by nutritional regulation. MAIN METHODS: Initially, through MTT and LDH assay revealed that Zn supplementation significantly suppressed OTA-induced cytotoxicity in MDCK cells. Then, the production of reactive oxygen species (ROS) was detected by using a DCFH-DA assay. Annexin V-FITC/PI, Hoechst 33258 staining and Flow cytometry were used to detect the apoptosis. The expressions of apoptosis-related molecules were determined by RT-PCR, Western blotting. Interestingly, OTA treatment slightly increased the levels of Metallothionein-1 (MT-1) and Metallothionein-2 (MT-2) by using RT-PCR, Western blotting assay; while Zn supplementation further improved the increase of MT-1 and MT-2 induced by OTA. However, the inhibitive effects of Zn supplementation were significantly blocked after double knockdown of MT-1 and MT-2 by using Small Interfering RNA (siRNA) Transfection method. KEY FINDINGS: Our study provides supportive data for the potential roles of Zn in reducing OTA-induced oxidative stress and apoptosis in MDCK cells. SIGNIFICANCE: Zn is one of the key structural components of many proteins, which plays an important role in several physiological processes such as cell survival and apoptosis. This metal is expected to contribute to the conservative and adjuvant treatment of kidney disease and should therefore be investigated further.


Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Metalotioneína/genética , Ocratoxinas/toxicidade , Substâncias Protetoras/farmacologia , Zinco/farmacologia , Animais , Citoproteção/efeitos dos fármacos , Cães , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Madin Darby de Rim Canino , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
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