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1.
Plast Reconstr Surg ; 144(4): 847-853, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31568289

RESUMO

BACKGROUND: Abdominoplasty is a safe, efficacious body contouring procedure commonly performed on patients after massive weight loss or pregnancy, or because of general aging. However, complication rates and patient satisfaction levels remain largely unexplored for the overweight and obese patient population. The purpose of this study was twofold: to determine the complication rate and to gauge the psychological impact of abdominoplasty in the overweight or obese patient. METHODS: A retrospective review was conducted of consecutive overweight and obese patients undergoing abdominoplasty or panniculectomy over a 12-year period from January of 2004 to December of 2016. Patient medical records were reviewed to identify patient demographics and comorbidities, operative details, and postoperative course. A patient survey was used to assess satisfaction, personal experience with complications, and the recovery process. RESULTS: Forty-six total patients underwent abdominoplasty or panniculectomy during the 12-year period and met the criterion of body mass index greater than or equal to 25 kg/m. The average patient body mass index was 32.0 kg/m, with the majority of the patients categorized as overweight. The average abdominal resection weight was 4834.9 g. Major complications, defined as complications requiring return to the operating room, occurred in four patients (8.7 percent). Minor complications, defined as complications that could be handled in an office setting, occurred in 18 patients (39.1 percent). Thirty-six patients (78.3 percent) responded to the survey. The overwhelming majority of patients who responded to the survey [n = 35 (97.2 percent)] stated that they were satisfied with the final outcome and would choose to have the procedure again. CONCLUSION: Abdominoplasty and panniculectomy in overweight and obese patients are associated with an elevated complication rate, yet patient satisfaction is overwhelmingly high, suggesting the viability of body contouring procedures in this patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31573846

RESUMO

Interleukin-8 (IL-8,also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in db/db mice. The db/m and db/db mice were injected with G31P or equivalent normal saline for six weeks. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated AKT level. The expressions of several genes encoding proteins involved in de novo lipogenesis (DNL) were decreased in G31P-treated db/db mice. Meanwhile, immune cells infiltration and cytokines release were attenuated in db/db mice with G31P treatment. G31P also improved the ratio of pro-inflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates inflammation-associated metabolic disorders via inhibition of CXCR1 and CXCR2 pathways. These data suggest the selective inhibition of CXC chemokines may have therapeutic effect on inflammation and its related metabolic syndrome.

3.
Neuroepidemiology ; : 1-13, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574510

RESUMO

BACKGROUND AND AIMS: The impact of statin on dementia risk reduction has been a subject of debate over the last decade, but the evidence remains inconclusive. Therefore, we performed a meta-analysis of relevant observational studies to quantify the magnitude of the association between statin therapy and the risk of dementia. METHODS: We systematically searched for relevant studies published from January 2000 to March 2018 using EMBASE, Google, Google Scholar, PubMed, Scopus, and Web of Science. Two authors performed study selection, data abstraction, and risk of bias assessment. We then extracted data from the selected studies and performed meta-analysis of observational studies using a random-effects model. Subgroup and sensitivity analyses were also conducted. RESULTS: A total of 30 observational studies, including 9,162,509 participants (84,101 dementia patients), met the eligibility criteria. Patients with statin had a lower all-caused dementia risk than those without statin (risk ratio [RR] 0.83, 95% CI 0.79-0.87, I2 = 57.73%). The overall pooled reduction of Alzheimer disease in patients with statin use was RR 0.69 (95% CI 0.60-0.80, p < 0.0001), and the overall pooled RR of statin use and vascular dementia risk was RR 0.93 (95% CI 0.74-1.16, p = 0.54). CONCLUSION: This study suggests that the use of statin is significantly associated with a decreased risk of dementia. Future studies measuring such outcomes would provide useful information to patients, clinicians, and policymakers. Until further evidence is established, clinicians need to make sure that statin use should remain restricted to the treatment of cardiovascular disease.

4.
Medicine (Baltimore) ; 98(39): e17124, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574812

RESUMO

INTRODUCTION: Spasticity is the most common complication after stroke, which is the main obstacle in the recovery of motor function. Spasticity seriously affects the quality of life and brings a heavy burden to families and society. Acupuncture is an effective method for stroke. However, whether acupuncture is effective for poststroke spasticity is still unknown. The purpose of this systematic review (SR) is to evaluate the effectiveness and safety of acupuncture for poststroke spasticity. METHODS AND ANALYSIS: We will search the following databases from inception to July 2019: China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang Data, the Chinese Science and Technology Periodical Database (VIP), PubMed, Embase, The Cochrane Library, and Web of Science. All relevant randomized controlled trials (RCTs) utilizing acupuncture for poststroke spasticity will be included. The primary outcome is the modified Ashworth scale. Secondary outcomes include composite spasticity scale, clinic spasticity index, electromyographic activity, Hoffmann reflex activity, or other spasticity-related outcomes. Study selection, data extraction, and quality assessment will be performed independently by 2 reviewers. Assessment of risk of bias and data synthesis will be conducted using Review Manager V5.3 software. ETHICS AND DISSEMINATION: The ethical approval is not required since SR is based on published studies. The results of this SR will be published in a peer-reviewed scientific journal according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. PROSPERO REGISTRATION NUMBER: CRD42019129779.

5.
Environ Technol ; : 1-31, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566478

RESUMO

Based on batch experiments, we investigate the adsorption characteristics of Pb(II), Cd(II) and Cu(II) on multi-walled carbon nanotube-hydroxyapatite (MWCNT-HAP) composites in detail and explore the effects of the solid-to-liquid ratio, pH, the ionic strength, reaction time and temperature on adsorption. The results show that the adsorption on MWCNT-HAP follows Pb(II)>Cu(II)>Cd(II). With an increasing solid-to-liquid ratio, the adsorption quantity of Pb(II), Cd(II) and Cu(II) on MWCNT-HAP decreases, whereas the removal efficiency increases. The optimal pH for adsorption is 4.0~6.0. The effect of the ionic strength on the adsorption of Cd(II) is pronounced, whereas that on the adsorption of Pb(II) and Cu(II) is small. In the single-component system and ternary-component system, the adsorption processes for Pb(II), Cd(II) and Cu(II) on MWCNT-HAP have fast kinetics, and the pseudo-second-order kinetics model can well describe the adsorption kinetics of the three heavy metals. The adsorption of Pb(II), Cd(II) and Cu(II) on MWCNT-HAP is spontaneous and endothermic, and the Langmuir model can well simulate the isothermal adsorption of Pb(II) and Cu(II), whereas the Langmuir and Freundlich models can be used to describe the isothermal adsorption of Cd(II).

6.
Sci Rep ; 9(1): 14052, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575877

RESUMO

Titanium (Ti) is the widely used implant material in clinic, however, failures still frequently occur due to its bioinertness and poor antibacterial property. To improve the biological and antibacterial properties of Ti implants, micro-nanostructured hydroxyapatite (HA) coating was prepared on Ti surface by micro-arc oxidation (MAO), and then the antibacterial agent of chitosan (CS) was loaded on the HA surface through dip-coating method. The results showed that the obtained HA/CS composite coating accelerated the formation of apatite layer in SBF solution, enhanced cell adhesion, spreading and proliferation, and it also inhibited the bacterial growth, showing improved biological and antibacterial properties. Although, with the increased CS amount, the coverage of HA coating would be enlarged, resulting in depressed biological property, however, the antibacterial property of the composite coating was enhanced, and the cytotoxicity about CS was not detected in this work. In conclusion, the HA/CS coating has promising application in orthopedics, dentistry and other biomedical devices.

7.
Curr Eye Res ; : 1-7, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31576759

RESUMO

Purpose: The disruption of retinal pigment epithelium (RPE) barrier may perform a crucial role in the pathogenesis of diabetic retinopathy (DR). AMPK exerts several salutary effects on photoreceptors and the RPE function and improves retina abnormalities. The current study aimed to determine whether sodium tanshinone IIA silate (STS) has an inhibitory effect on ARPE-19 cell monolayer permeability under high glucose conditions, and establish the underlying mechanism. Methods: We used a model of high glucose (25 mmol glucose, HG) condition mimicking diabetes in ARPE-19 cells, to assess the protective effects of STS. The barrier function of RPE cells were measured by Transepithelial Electrical Resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran permeability. The interaction of NF-κB p65 and p300 were tested using immunoblotting and immunoprecipitation and immunofluorescence assay. Protein levels were assayed using Western blot. Results: We found STS promoted the phosphorylation of AMP-activated protein kinase (AMPK) at T172 in RPE cells, and STS treatment thus inhibited ARPE-19 cell monolayer permeability under HG condition, similar to the permeability under normal glucose (5.5 mmol glucose, NG). Moreover, we found that STS obviously prevented the colocalization of NF-κB and p300, and significantly inhibited their binding, subsequent decreased ARPE-19 cell monolayer permeability. Notably, Compound C (CC), a specific inhibitor of AMPK, blocked STS-mediated inhibition of ARPE-19 cell monolayer permeability. Conclusions: STS inhibited HG-induced RPE permeability possibly through the reduction of NF-κB activation via the AMPK/p300 pathway. The protective effects of STS were attained through the suppression of p300-mediated NF-κB acetylation and STS might be utilized for treatment of DR, in terms of preventing inflammation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31577407

RESUMO

In this work, thin-film transistor (TFT) gas sensor based on p-N heterojunction is fabricated by stacking chemical vapor deposition (CVD)-grown tungsten disulfide (WS2) with sputtered indium-gallium-zinc-oxide (IGZO) film. To the best of our knowledge, the present device has the best NO2 gas sensor response comparing to all the gas sensors based on transition metal dichalcogenides (TMDCs) materials. The gas sensing response is investigated under different NO2 concentrations, adopting heterojunction device mode and a transistor mode. High sensing response is obtained of p-N diode in the range of 1-300 ppm with receptivity associated sensitivity values of 230% for 5 ppm and 18170% for 300 ppm. On the transistor mode, the gas sensing response can be modulated by the gate bias, the transistor shows an ultra-high response after exposure to NO2, with sensitivity values of 6820% for 5 ppm and 499400% for 300 ppm. Interestingly, the transistor has a typical ambipolar-behaviour under dry air, while the transistor becomes p-type as the amount of NO2 increases. The assembly of these results demonstrates that the WS2/IGZO device is a promising platform for the NO2 gas detection, and its gas-modulated transistor properties show a potential application in tunable engineering for 2D materials heterojunction-based transistor device.

9.
Medicine (Baltimore) ; 98(40): e17461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577776

RESUMO

Antidiabetic medications are commonly used around the world, but their safety is still unclear. The aim of this study was to investigate whether long-term use of insulin and oral antidiabetic medications is associated with cancer risk.We conducted a well-designed case-control study using 12 years of data from Taiwan's National Health Insurance Research Database and investigated the association between antidiabetic medication use and cancer risk over 20 years. We identified 42,500 patients diagnosed with cancer and calculated each patient's exposure to antidiabetic drugs during the study period. We matched cancer and noncancer subjects matched 1:6 by age, gender, and index date, and used Cox proportional hazard regression and conditional logistic regression, adjusted for potential confounding factors, that is, medications and comorbid diseases that could influence cancer risk during study period.Pioglitazone (adjusted odds ratio [AOR], 1.20; 95% confidence interval [CI], 1.05-1.38); and insulin and its analogs for injection, intermediate or long acting combined with fast acting (AOR, 1.22; 95% CI, 1.05-1.43) were significantly associated with a higher cancer risk. However, metformin (AOR, 1.00; 95% CI, 0.93-1.07), glibenclamide (AOR, 0.98; 95% CI, 0.92-1.05), acarbose (AOR, 1.06; 95% CI, 0.96-1.16), and others do not show evidence of association with cancer risk. Moreover, the risk for specific cancers among antidiabetic users as compared with nonantidiabetic medication users was significantly increased for pancreas cancer (by 45%), liver cancer (by 32%), and lung cancer (by 18%).Antidiabetic drugs do not seem to be associated with an increased cancer risk incidence except for pioglitazone, insulin and its analogs for injection, intermediate or long acting combined with fast acting.

10.
J Am Chem Soc ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577900

RESUMO

Programming and controlling molecular recognition in aqueous solutions is increasingly common, but creating supramolecular sensors that detect analytes in biologically relevant solutions remains a non-trivial task. We report here a parallel synthesis-driven approach to create a family of self-assembling dimeric sensors that we call DimerDyes, and its use for the rapid identification of salt-tolerant sensors for illicit drugs. We developed an efficient method that involves parallel synthesis and screening in crude form without the need to purify each potential sensor. Structurally diverse "hit" DimerDyes were re-synthesized, purified and were each shown to assemble into homodimers in water in the programmed way. DimerDyes provided a "turn-on" fluorescence detection of multiple illicit drugs at low micromolar concentrations in water and in saliva. The combination of multiple agents into a sensor array was successfully able to detect and discriminate between closely related drugs and metabolites in multiple important drug families.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31581096

RESUMO

In this study, we design a hardware accelerator for a widely used sequence alignment algorithm, the basic local alignment search tool for proteins (BLASTP). The architecture of the proposed accelerator consists of five stages: a new systolic-array-based one-hit finding stage, a novel RAM-REG-based two-hit finding stage, a refined ungapped extension stage, a faster gapped extension stage, and a highly efficient parallel sorter. The system is implemented on an Altera Stratix V FPGA with a processing speed of more than 500 giga cell updates per second (GCUPS). It can receive a query sequence, compare it with the sequences in the database, and generate a list sorted in descending order of the similarity scores between the query sequence and the subject sequences. Moreover, it is capable of processing both query and subject protein sequences comprising as many as 8192 amino acid residues in a single pass. Using data from the National Center for Biotechnology Information (NCBI) database, we show that a speed-up of more than 3X can be achieved with our hardware compared to the runtime required by BLASTP software on an 8-thread Intel Xeon CPU with 144 GB DRAM.

12.
Chem Pharm Bull (Tokyo) ; 67(10): 1072-1075, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582627

RESUMO

Shikonin, a natural naphthoquinone, has attracted much attention due to its various biological activities. Two shikonin glucosides, shikonin-1',8-di-O-ß-D-glucopyranoside (1) and shikonin-1'-O-ß-D-glucopyranoside (2), were biosynthesized through in vitro enzymatic glycosylation and their structures were elucidated using spectroscopic techniques. The water-solubility and stability of compounds 1 and 2 were significantly higher than those of the parent compound. Furthermore, compound 2 showed moderate cytotoxicity against six cancer cell lines, with IC50 values ranging from 36.10 to 67.47 µM. This research indicated that in vitro enzymatic glycosylation of shikonin is an effective strategy to improve it water solubility and chemical stability.

13.
Cell Death Dis ; 10(10): 744, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582720

RESUMO

We investigated the mechanism underlying the effect of a combination treatment of 125I radioactive seed implantation and lobaplatin (LBP) in hepatocellular carcinoma. The effects of administration of HCC cells and subcutaneous tumor model of mice with different doses of 125I or a sensitizing concentration of LBP alone, or in combination, on cellular apoptosis and proliferation were analyzed and it was confirmed that LBP promotes 125I-induced apoptosis and inhibition of proliferation of HCC. Furthermore, isobaric tag for relative and absolute quantification labeling analyses suggested that 125I promoted the apoptosis and inhibition of proliferation of HCC cells by upregulating the expression of PERK-eIF2α-ATF4-CHOP pathway, a well-known apoptosis-related pathway. Moreover, LBP was found to boost the 125I-induced upregulation of this pathway and increase the apoptosis. Our data indicate that LBP promotes the apoptotic and anti-proliferative effects of 125I and provide a firm foundation for better clinical application of this combination therapy.

14.
Medicine (Baltimore) ; 98(38): e17176, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567957

RESUMO

BACKGROUND: The aim of this study was to investigate the use of pretreatment platelet-to-lymphocyte ratio (PLR) as a prognostic marker in patients with nasopharyngeal carcinoma (NPC). METHODS: A literature search was conducted using online databases such as MEDLINE, EMBASE, Cochrane Library, and WangFang. Overall survival (OS), progression-free survival (PFS), and clinicopathological features were generated and compared. RESULTS: Ten studies that included 3388 patients were analyzed in this meta-analysis. Among them, 8 studies with 3033 patients with NPC investigated the prognostic role of PLR for OS and showed that elevated PLR was associated with poor OS (HR: 1.77, 95% CI: 1.46-2.15, P < .001). Five studies that included 1156 patients investigated the role of PLR in predicting PFS, and showed that high PLR was associated with poor PFS (HR: 1.65, 95% CI: 1.26-2.17, P < .001). Moreover, high PLR correlated with the N stage (N2-3 vs N0-1; OR: 1.55, 95% CI: 1.02-2.34, P = .04). CONCLUSION: Our study suggested that high PLR is associated with worse prognosis in patients with NPC. Pretreatment PLR could serve as a simple, promising indicator for prognostic evaluation in patients with NPC.


Assuntos
Contagem de Linfócitos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Contagem de Plaquetas , Plaquetas , Humanos , Linfócitos , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Análise de Sobrevida
16.
Water Res ; 167: 115137, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31585386

RESUMO

Two submerged anaerobic membrane bioreactors (AnMBRs) with and without powdered activated carbon (PAC) were studied to revisit the effect of PAC on membrane fouling performance by long-term operation when treating synthetic sewage. The results showed that PAC remained efficient for membrane fouling control after long-term operation (over 140 d), and it reduced the fouling rate at a hydraulic retention time of 8 h from 3.12 to 0.89 kPa/d. PAC mainly mitigated the membrane fouling by restraining the formation of a cake layer while generating a gel layer on the membrane surface, which was attributed to the PAC-induced microbial community change in mixed liquor and the membrane surface. Microbial community analysis indicated the genera Pseudomonas (26.5%) and Methanothrix (79.21%) were the predominant bacteria and archaea, respectively, in the gel layer, and this result is completely different from the presence of a high abundance of Levilinea (7.1%), Aminivibrio (4.9%) and Methanothrix (90.04%) in the cake layer on the membrane surface without PAC. The significant difference in the predominant microbes in the membrane surface layer was attributed to the reduced enrichment of Levilinea and Methanothrix with PAC addition.

17.
Ecotoxicol Environ Saf ; 185: 109720, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585392

RESUMO

INTRODUCTION: Selenium plays important roles in antagonizing the toxicity of methylmercury. The underlying mechanism for the antagonism between Se and MeHg is still not fully understood. OBJECTIVE: The role of gut flora against the toxicity of environmental contaminants is receiving more and more attention. The objective of this study was to investigate the role of Se against MeHg-poisoning in the modulation of gut flora and the decomposition of MeHg. METHODS: MeHg-poisoned rats were treated with sodium selenite every other day for 90 days. Fecal samples were collected on Day 8, 30, 60 and 90. Gut flora in feces was determined using 16S rRNA gene profiling, and the concentrations of Se and total mercury (THg) were measured by ICP-MS, and the concentration of MeHg was measured by CVAFS. RESULTS: Gut flora at both the ranks of phylum and genus in the MeHg-poisoned rats after Se treatment was modulated towards that in the control group, suggesting the restoration of the profile of gut flora. Increased THg was found in fecal samples after Se treatment on day 30. The percentage of MeHg (of total mercury) in the MeHg-poisoned group was in the range of 81-105% while it was 65-84% in the Se treatment group on different days, suggesting the increased decomposition of MeHg in MeHg-poisoned rats after Se treatment. CONCLUSIONS: This study suggests that MeHg poisoning damaged the abundance of gut flora and decreased their capacity for the decomposition of MeHg. After Se treatment, the abundance of gut flora was partially restored and the decomposition and excretion of MeHg was enhanced. These findings suggest that the modulation of gut flora may be one way to promote the health status in MeHg-poisoned rats and possibly in human beings.

18.
Nat Commun ; 10(1): 4574, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594929

RESUMO

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor.

19.
J Cell Physiol ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595984

RESUMO

Osteosarcoma (OS) is the most common bone tumor that occurs predominantly in children and teenagers. Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt/ß-catenin signaling pathway is frequently observed in OS. We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt-related transcription factor 2 via the AKT/GSK-3ß/ß-catenin signaling pathway in OS. However, the precise role of T cell factors/lymphoid enhancer-binding factor (TCFs/LEF) family members, which are the major binding complex of ß-catenin, in OS is poorly understood. In the present study, we first demonstrated that TCF-1 is overexpressed in OS compared with other bone tumors. Knockdown of TCF-1 significantly induced cell cycle arrest, severe DNA damage, and subsequent caspase-3-dependent apoptosis. Interestingly, coexpression of HSP90 and TCF-1 was observed in OS, and mechanistically, we demonstrated that TCF-1 expression is regulated by HSP90 either through a ß-catenin-dependent mechanism or a direct degradation of the proteasome. We also found that overexpression of TCF-1 partially abolishes the apoptosis induced by HSP90 inhibition. Furthermore, we provided evidence that p53, but not miR-34a, plays a crucial role in the HSP90-regulated TCF-1 expression and subsequent apoptosis. Given the diverse combination regimens of HSP90 inhibition with some other treatments, we propose that the p53 status and the expression level of TCF-1 should be taken into consideration to enhance the therapeutic efficacy of HSP90 inhibition.

20.
Aging (Albany NY) ; 112019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596731

RESUMO

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-α-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFκB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.

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