Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
1.
DNA Cell Biol ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32456459

RESUMO

Tumor necrosis factor-alpha (TNFα) is an inflammatory cytokine that regulates inflammation and tumor progression in non-small cell lung cancer (NSCLC). The higher levels of TNF α are known to induce expression of several genes such as TNFα-induced protein 2 (TNFAIP2) with a largely unknown role in NSCLC. We provide the preliminary evidence for the role of TNFAIP2 in NSCLC progression and its epigenetic regulation mediated by microRNA, miR-145-5p. The expression of TNFAIP2 was confirmed using quantitative real-time PCR, immunohistochemistry, and Western blot in NSCLC tissue and paired adjacent normal tissue. All in vitro assays were undertaken in A549 and H23 cells and chemoresistance assays were undertaken in A549/Cisplatin (DDP) and H23/DDP cell types. TNFAIP2 silencing was undertaken using lipofectamine transfection of specific siRNA. Cells were co-transfected with miR-145-5p, and TNFAIP2-3' untranslated region (UTR) or TNFAIP2 with mutated 3'UTR using the luciferase vector pGL. Cell viability, transwell migration, and invasion were assessed. The role of caspase 3 proteins in cell viability was ascertained using Western blot. The tumor tissues (and cisplatin-resistant cell lines A549/DDP and H23/DDP) expressed significantly higher levels of TNAIP2 mRNA and protein. Silencing of TNFAIP2 resulted in reduced cell viability, reduced invasion, and migration in vitro. Silencing of TNFAIP2 in A549/DDP and H23/DDP had higher expression of TNFAIP2, reduced cell viability, and increased induction of caspase 3. MiR-145-5p binds to the 3'UTR of TNFAIP2. Overexpression of MiR-145-5p reduced expression of TNFAIP2, decreased cell viability, reduced cell migration and invasion, and significantly reduced expression of caspase 3 protein. TNFAIP2 mediates tumorigenesis in NSCLC through, not completely known pathways. miR-145-5p negatively regulates TNFAIP2 expression. miR-145-5p-mediated therapies may be explored in NSCLC.

2.
BMC Cardiovasc Disord ; 20(1): 177, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299373

RESUMO

After the publication of the original article [1], we were notified that one of the corresponding author's name and her related institution were wrongly spelled.

3.
Sci Rep ; 10(1): 5324, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32210275

RESUMO

Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer progression, including FOXO4, MDM2, N-Myc, and PTEN. The multi-substrate nature of USP7, combined with the modest potency and selectivity of early generation USP7 inhibitors, has presented a challenge in defining predictors of response to USP7 and potential patient populations that would benefit most from USP7-targeted drugs. Here, we describe the structure-guided development of XL177A, which irreversibly inhibits USP7 with sub-nM potency and selectivity across the human proteome. Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of ~500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells. Together, these findings suggest TP53 mutational status as a biomarker for response to USP7 inhibition. We find that Ewing sarcoma and malignant rhabdoid tumor (MRT), two pediatric cancers that are sensitive to other p53-dependent cytotoxic drugs, also display increased sensitivity to XL177A.

4.
Talanta ; 211: 120660, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32070626

RESUMO

An electrochemiluminescence and photothermal immunosensor based on a dual-modality integrated probe was proposed for sensitive and reliable detection of lipolysis stimulated lipoprotein receptor (LSR), a new biomarker of ovarian cancer. Black phosphorous quantum dots (BPQDs) possess fascinating electrochemical property and unique photothermal effect, which could not only enhance ECL signal of N-(4-aminobutyl)-N-ethylisoluminol (ABEI) through accelerating dissolved O2 evolution but also realize temperature signal output by converting laser energy into heat. Furthermore, NiFe2O4 nanotubes (NiFe2O4 NTs) have large specific surface area and favorable adsorption ability, which could increase the immobilized amount of ABEI and BPQDs, further strengthening ECL and temperature signal. As a result, a dual-mode immunosensor was constructed and realized ECL and temperature dual signal to detect LSR, making the results more reliable. This work provided a new thought for the development of sensitive and accurate sensors and was expected to employ for determination of other biomarkers.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32101408

RESUMO

Thermoelectric (TE) materials have attracted extensive interest because of their ability to achieve direct heat-to-electricity conversion. They provide an appealing renewable energy source in a variety of applications by harvesting waste heat. The record-breaking figure of merit reported for single crystal SnSe has stimulated related research on its polycrystalline counterpart. Boosting the TE conversion efficiency requires increases in the power factor and decreases in thermal conductivity. It is still a big challenge, however, to optimize these parameters independently because of their complex interrelationships. Herein, we propose an innovative approach to decouple electrical and thermal transport by incorporating carbon fiber (CF) into polycrystalline SnSe. We show that the incorporation of highly conductive CF can successfully enhance the electrical conductivity, while greatly reducing the thermal conductivity of polycrystalline SnSe. As a result, a high TE figure-of-merit (zT) of 1.3 at 823 K is obtained in p-type SnSe/CF composite polycrystalline materials. Furthermore, SnSe samples incorporated with CFs exhibit superior mechanical properties, which are favorable for device fabrication applications. Our results indicate that the dispersion of CF can be a good way to greatly improve both TE and mechanical performance.

6.
J Diabetes Res ; 2020: 2532171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090117

RESUMO

Objective: The purpose of this study was to assess the effects of glucose fluctuation targeted intervention on neurologic function, independent living skills, and quality of life in type 2 diabetes patients following the first episode of cerebral infarction (CI). Methods: This was a randomized control trial. Following confirmed cerebral infarction, 75 patients with type 2 diabetes were randomized into 2 groups: control group (n = 37) with usual care, focused on hemoglobin A1c (HbA1c) control, targeting A1c < 7%, and intervention group (n = 37) with usual care, focused on hemoglobin A1c (HbA1c) control, targeting A1c < 7%, and intervention group (. Results: After 6 months, data from 63 patients were analyzed (30 in the control group, 33 in the intervention group). There was no difference (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (P > 0.05) in the reduction of A1c between the 2 groups, but the reductions of LAGE (. Conclusion: Glucose fluctuation targeted intervention can improve nerve function for patients with T2DM following the first CI episode. This trial is registered with NCT03932084.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32078545

RESUMO

Temporal cues embedded in videos provide important clues for person Re-Identification (ReID). To efficiently exploit temporal cues with a compact neural network, this work proposes a novel 3D convolution layer called Multi-scale 3D (M3D) convolution layer. The M3D layer is easy to implement and could be inserted into traditional 2D convolution networks to learn multi-scale temporal cues by end-to-end training. According to its inserted location, the M3D layer has two variants, i.e., local M3D layer and global M3D layer, respectively. The local M3D layer is inserted between 2D convolution layers to learn spatial-temporal cues among adjacent 2D feature maps. The global M3D layer is computed on adjacent frame feature vectors to learn their global temporal relations. The local and global M3D layers hence learn complementary temporal cues. Their combination introduces a fraction of parameters to traditional 2D CNN, but leads to the strong multi-scale temporal feature learning capability. The learned temporal feature is fused with a spatial feature to compose the final spatial-temporal representation for video person ReID. Evaluations on four widely used video person ReID datasets, i.e., MARS, DukeMTMC-VideoReID, PRID2011, and iLIDS-VID demonstrate the substantial advantages of our method over the state-of-the art. For example, it achieves rank1 accuracy of 88.63% on MARS without re-ranking. Our method also achieves a reasonable trade-off between ReID accuracy and model size, e.g., it saves about 40% parameters of I3D CNN.

8.
Zhongguo Zhen Jiu ; 40(1): 54-7, 2020 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-31930900

RESUMO

The value of the "touching-bone" acupuncture technique in clinical application was explained through the investigation on the origin of the theory of the "touching-bone" acupuncture technique, the analysis on the characteristics of acupoint selection, the introduction of clinical characteristics and the discussion on the mechanism of acupuncture in treatment. The "touching-bone" acupuncture technique refers to deep needling method, originated from the short needling and shu needling of the ancient needling methodslisted in the Internal Classic. The target points are the reaction sites on meridian near to bone and the attachments of soft tissues on bone. During the needle insertion, the needle tip is thrust deeply to the bone or the needle body is closely attached to the bone so as to stimulate periosteum specifically. This needling technique contributes to the satisfactory effect on spasmodic, deep-located and intractable pain disorder, motor system diseases, mental diseases and cerebral diseases, etc. Hence, this acupuncture technique deserves to be promoted in clinical application and explored in research.


Assuntos
Terapia por Acupuntura , Meridianos , Agulhas
9.
Metab Brain Dis ; 35(3): 473-482, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31997266

RESUMO

Spinal cord injury (SCI) is the major cause of the spinal damage affecting motor and sensory function. Thus, the present study was conducted to investigate the effect of D-pinitol (PN) on spinal cord injury in rats. The PN showed to recover motor function near to normal via modulating oxidative stress, inflammatory response and cellular apoptosis in SCI rats. PN also causes modulation of Bcl2 family proteins and reduces the level of NF-ĸB and LOX-1 in dose dependent manner. The PN causes reduction of NLRP3, TNF-α and iNOS, with increase in caspase-1 together with modulation of MAPK mediators. It has been suggested that, D-pinitol exert protective action against SCI via inhibition of apoptosis, inflammation and oxidative stress, via modulating Bcl-2 genes and MAPK pathway.

10.
Anal Chem ; 92(5): 3923-3931, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-31944669

RESUMO

Interactions between glycosphingolipids (GSLs) on the surfaces of cells and glycan-binding proteins (GBPs) mediate a wide variety of essential and pathological processes. Despite the biological importance of these interactions, the GSL ligands of most GBPs remain to be identified and the mechanisms controlling recognition of GSLs are incompletely understood. Recently, it was suggested that, when present together with high affinity ligands, low affinity GSL ligands can contribute significantly to the binding of GBPs with multiple binding sites through a process called heteromultivalent binding. Here, with goal of directly establishing the existence of heteromultivalent GSL interactions and elucidating the mechanism underlying their formation, we investigated cholera toxin B subunit homopentamer (CTB5) binding to ganglioside mixtures in model membranes (nanodiscs) using native mass spectrometry (MS) and competitive ligand binding. Electrospray ionization (ESI)-MS analysis revealed that the presence of the high affinity ligand GM1 (at substoichiometric amounts relative to binding sites) in the nanodisc promotes GD1b binding to CTB5; no GD1b binding was detected in the absence of GM1. No direct ESI-MS evidence of CTB5 binding to the other five gangliosides tested, alone or present together with GM1 in the nanodiscs, was observed. Affinity measurements, carried out using the proxy ligand ESI-MS binding assay, confirmed that GD1b binding to CTB5 is dramatically enhanced (>1000-times higher affinity compared to the GD1b oligosaccharide affinity) when present with GM1. NDs containing GM1 and GM2, GD1a, or GT1b also exhibited enhanced CTB5 binding, however, the effect was smaller. The results of molecular dynamics simulations performed on ganglioside-containing nanodiscs suggest that the participation of low affinity ligands in heteromultivalent binding with GM1 may be regulated by the positions of the internal Gal-linked Neu5Ac residues of the gangliosides relative to the membrane surface.

11.
J Diabetes ; 12(1): 25-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31141300

RESUMO

BACKGROUND: It is clear that aerobic training (AT) can delay pancreatic exhaustion and slow the progression from prediabetes to type 2 diabetes (T2D), but there is little information regarding the effects of resistance training (RT) in people with prediabetes. This study compared the effectiveness of RT and AT in improving metabolic control and protecting ß-cell function in people with prediabetes. METHODS: Chinese subjects (n = 248) with prediabetes were randomized to three groups: AT (n = 83), RT (n = 82) and control (n = 83). Subjects in the RT group performed 13 different resistance exercises per session using an elastic string. Those in the AT group performed aerobic exercises at 60%-70% of maximum heart rate. In both cases, exercises were performed three times per week for a period of 6 months. The primary outcome was improvement in metabolic control. Longitudinal changes between groups were tested using repeated-measures analysis of variance. RESULTS: Of the initial 248 participants, 217 finished the study, but all participants were included in the intention-to-treat analyses. There were no significant differences in demographic characteristics among the RT, AT, and control groups (P > 0.05). Changes in HbA1c were not significantly greater in RT than AT cohort (P = 0.059), but the decrease in HbA1c in both exercise groups was higher than in the control group (P < 0.05). CONCLUSIONS: In subjects with prediabetes, RT appears to improve metabolic control and preserve ß-cell function comparable to AT.

12.
Clin Genet ; 97(3): 383-395, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31758797

RESUMO

The COL2A1 gene encodes the alpha-1 chain of type II procollagen. Type II collagen, comprised of three identical alpha-1 chains, is the major component of cartilage. COL2A1 gene variants are the etiologies of genetic diseases, termed type II collagenopathies, with a wide spectrum of clinical presentations. To date, at least 460 distinct COL2A1 mutations, identified in 663 independent probands, and 21 definite disorders have been reported. Nevertheless, a well-defined genotype-phenotype correlation has not been established, and few hot spots of mutation have been reported. In this study, we analyzed data of COL2A1 variants and clinical information of patients obtained from the Leiden Open Variation Database 3.0, as well as the currently available relevant literature. We determined the characteristics of the COL2A1 variants and distributions of the clinical manifestations in patients, and identified four likely genotype-phenotype correlations. Moreover, we classified 21 COL2A1-related disorders into five categories, which may assist clinicians in understanding the essence of these complex phenotypes and prompt genetic screening in clinical practice.

13.
BMC Cardiovasc Disord ; 19(1): 301, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31881945

RESUMO

BACKGROUND: Cardiovascular disease has become a serious public health problem in recent years in China. The aim of the study was to examine sex differences in cardiovascular risk factors and 10-year ischemic cardiovascular disease (ICVD) risk in Chinese patients with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). METHODS: This was a multi-site retrospective case-control study conducted from April-November 2016 using an electronic medical record database, involving 217 PreDM and 900 T2DM patients admitted to endocrinology units in four hospitals in China. CVD risk was estimated using the Chinese 10-year ICVD risk model. The differences in 10-year absolute ICVD risk according to PreDM, T2DM < 1 year, T2DM 1-5 years or T2DM ≥5 years and sex were analyzed using ANOVA. RESULTS: When compared to PreDM females, males with PreDM had significantly higher 10-year ICVD risk In contrast, the opposite pattern of 10-year ICVD risk was observed in T2DM; males had significantly lower 10-year ICVD risk. Moreover, compared to T2DM females, males with T2DM had a lower proportion s with moderate or greater ICVD risk (p < 0.001). When compared to PreDM males, males with T2DM < 1 year, and with T2DM 1-5 years had no difference in 10-year ICVD risk, but had higher ICVD risk with T2DM ≥5 years (p < 0.05). Compared to PreDM females, females with T2DM in all subgroups had higher ICVD risk (p < 0.05). Among those with T2DM, hypertension rates of awareness, treatment and control were 78.60%, 65.38% and 31.10%, respectively; hyperlipidemia rates of awareness, treatment and control were lower (29.15%, 8.30% and 3.47%, respectively). Females with T2DM had higher prevalence, awareness and treatment of hypertension and hyperlipidemia than males with T2DM (p < 0.001). CONCLUSIONS: There is a greater need for cardiovascular risk reduction programs for females with T2DM at diagnosis. Given the low numbers for awareness, treatment and control of hypertension and hyperlipidemia in both males and females, significant resources focused on them must be expended, specifically improving regular assessment of blood pressure and blood lipids. Strengthening the management of chronic diseases through adherence to evidence-based guidelines to enhance clinical treatment may reduce 10-year ICVD in patients with T2DM in China.

14.
Cell Death Dis ; 10(12): 893, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772150

RESUMO

Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.

15.
J Diabetes Res ; 2019: 8469739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737686

RESUMO

Objective: To examine the effects of resistance training relative to aerobic training on abdominal adipose tissue and metabolic variables in adults with prediabetes. Methods: 105 participants with prediabetes were randomized into the resistance training group (RT, n = 35), aerobic training group (AT, n = 35), and control group (CG, n = 35). The participants completed supervised 12-month exercise; the control group followed the primary lifestyle without exercise intervention. The primary outcomes were visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by computed tomography (CT). Secondary outcomes were body composition, lipid profile, and metabolic variables. Results: A total of 93 participants completed the study. There were nonsignificant differences between groups before intervention. After training, VAT decreased significantly in AT and RT compared with CG (P = 0.001 and P = 0.014, respectively). Although no significant difference in SAT was found across groups, SAT decreased significantly over time within each exercise group (all P = 0.001). Increase in muscle mass was greater in RT than that in AT and CG (P = 0.031 and P = 0.045, respectively). Compared with CG, fasting plasma glucose (FPG) decreased significantly in RT and AT (P = 0.003 and P = 0.014, respectively). There was a significant difference in the number of prediabetes who converted to diabetes among AT and RT, as compared with the control group (P = 0.031 and P = 0.011, respectively). No significant differences were observed in lipid, waist-to-hip ratio (WHR), body mass index (BMI), fasting insulin (FI), 2-hour postprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), HOMA-IR, and HOMA-ß across groups. Conclusion: Both aerobic training and resistance training are effective in reducing abdominal adipose tissue and fasting plasma glucose in adults with prediabetes. Importantly, resistance training but not aerobic training is effective in augmenting muscle mass. Trial Registration: The trial is registered with NCT02561377 (date of registration: 24/09/2015).

16.
Biosens Bioelectron ; 145: 111719, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563066

RESUMO

Simultaneous detection of free and complexed prostate-specific antigen (f-PSA and c-PSA) is critical to the prostate cancer (PCa) diagnostic accuracy for clinical samples with PSA values in the diagnostic gray zone between 4 and 10 ng mL-1. Herein, red and green magnetic-quantum dot nanobeads (MQBs) with superior magnetic property and high luminescence were fabricated via polyethyleneimine-mediated electrostatic adsorption of numerous quantum dots onto superparamagnetic Fe3O4 magnetic cores, and were conjugated with f-PSA antibody and c-PSA antibody, respectively, as versatile fluorescent probes in test strip for immune recognition, magnetic enrichment, and simultaneous detection of f-PSA and c-PSA analytes in complex biological matrix with t-PSA antibody on the test line. A low-cost and portable smartphone readout device with an application was also developed for the imaging of dual-color test strips and data processing. This assay can simultaneously detect f-PSA and c-PSA with the limits of detection of 0.009 ng mL-1 and 0.087 ng mL-1, respectively. Clinical serum samples of PCa and benign prostatic hyperplasia patients were evaluated to confirm the clinical feasibility. The results suggest that the proposed dual-color MQBs-based fluorescent lateral flow immunoassay is a promising point-of-care diagnostics technique for the accurate diagnosis of PCa even in resource-limited settings.

17.
Arterioscler Thromb Vasc Biol ; 39(10): 1986-1995, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31462090

RESUMO

OBJECTIVE: Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice. Approach and Results: We adapted our protocol for biliary cholesterol secretion with published methods for measuring transintestinal cholesterol elimination. Bile was diverted and biliary lipid secretion maintained by infusion of bile acid. The proximal small bowel was perfused with bile acid micelles. In high-fat, high-cholesterol-fed mice, the presence of a CETP transgene increased biliary cholesterol secretion at the expense of transintestinal cholesterol elimination. The increase in biliary cholesterol secretion was not associated with increases in hepatic SR-BI (scavenger receptor BI) or ABCG5 (ATP-binding cassette G5) ABCG8. The decline in intestinal cholesterol secretion was associated with an increase in intestinal Niemann-Pick disease, type C1, gene-like 1 mRNA. Finally, we followed the delivery of HDL (high-density lipoprotein) or LDL (low-density lipoprotein) cholesteryl esters (CE) from plasma to bile and intestinal perfusates. HDL-CE favored the biliary pathway. Following high-fat feeding, the presence of CETP directed HDL-CE away from the bile and towards the intestine. The presence of CETP increased LDL-CE delivery to bile, whereas the appearance of LDL-CE in intestinal perfusate was near the lower limit of detection. CONCLUSIONS: Biliary and intestinal cholesterol secretion can be simultaneously measured in mice and used as a model to examine factors that alter cholesterol elimination. Plasma factors, such as CETP, alter the route of cholesterol elimination from the body. Intestinal and biliary cholesterol secretion rates are independent of transhepatic or transintestinal delivery of HDL-CE, whereas LDL-CE was eliminated almost exclusively in the hepatobiliary pathway.

18.
Pathol Res Pract ; 215(10): 152591, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445716

RESUMO

The role of transforming growth factor beta (TGF-ß) in lung cancer is well known. TGF-ß-mediated cellular proliferation and angiogenesis through similar to mothers against decapentaplegic homolog 2 (Smad2) protein has also been well elucidated. Smad2 is a predicted target for a microRNAs, namely miR-433. microRNAs are a significant class of non-coding RNAs which play an important role in epigenetic regulation. Here, we show that miR-433 directly binds to Smad2, which is shown to be upregulated in non-small cell lung carcinomas (NSCLC). miR-433 expression is downregulated in NSCLC tissues and cells. Overexpression of miR-433 is associated with decreased expression of proteins - namely Cyclin D1, MMP-2/TIMP-2, and MMP-9, and consequently reduced cell proliferation and invasion phenotypes. Complementation of miR-433 leads to rescue of these disrupted phenotypes. miR-433 mediates its action via Smad2 and Id-1. miR-433 may be a candidate worth further exploration for its prognostic and therapeutic potential in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais/fisiologia , Proteína Smad2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Proteína Smad2/genética
19.
Curr Top Med Chem ; 19(16): 1399-1417, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31284862

RESUMO

The pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor (PAC1R, ADCYAP1R1) is a member of the vasoactive intestinal peptide (VIP)/secretin/glucagon family of G protein-coupled receptors (GPCRs). PAC1R has been shown to play crucial roles in the central and peripheral nervous systems. The activation of PAC1R initiates diverse downstream signal transduction pathways, including adenylyl cyclase, phospholipase C, MEK/ERK, and Akt pathways that regulate a number of physiological systems to maintain functional homeostasis. Accordingly, at times of tissue injury or insult, PACAP/PAC1R activation of these pathways can be trophic to blunt or delay apoptotic events and enhance cell survival. Enhancing PAC1R signaling under these conditions has the potential to mitigate cellular damages associated with cerebrovascular trauma (including stroke), neurodegeneration (such as Parkinson's and Alzheimer's disease), or peripheral organ insults. Conversely, maladaptive PACAP/PAC1R signaling has been implicated in a number of disorders, including stressrelated psychopathologies (i.e., depression, posttraumatic stress disorder, and related abnormalities), chronic pain and migraine, and metabolic diseases; abrogating PAC1R signaling under these pathological conditions represent opportunities for therapeutic intervention. Given the diverse PAC1R-mediated biological activities, the receptor has emerged as a relevant pharmaceutical target. In this review, we first describe the current knowledge regarding the molecular structure, dynamics, and function of PAC1R. Then, we discuss the roles of PACAP and PAC1R in the activation of a variety of signaling cascades related to the physiology and diseases of the nervous system. Lastly, we examine current drug design and development of peptides and small molecules targeting PAC1R based on a number of structure- activity relationship studies and key pharmacophore elements. At present, the rational design of PAC1R-selective peptide or small-molecule therapeutics is largely hindered by the lack of structural information regarding PAC1R activation mechanisms, the PACAP-PAC1R interface, and the core segments involved in receptor activation. Understanding the molecular basis governing the PACAP interactions with its different cognate receptors will undoubtedly provide a basis for the development and/or refinement of receptor-selective therapeutics.


Assuntos
Doenças Metabólicas/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Peptídeos/farmacologia , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Humanos , Doenças Metabólicas/metabolismo , Modelos Moleculares , Estrutura Molecular , Doenças do Sistema Nervoso/metabolismo , Peptídeos/síntese química , Peptídeos/química , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/química , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química
20.
Artigo em Inglês | MEDLINE | ID: mdl-31331878

RESUMO

The large pose variations and misalignment errors exhibited by person images significantly increase the difficulty of person Re-Identification (ReID). Existing works commonly apply extra operations like pose estimation, part segmentation, etc., to alleviate those issues and improve the robustness of pedestrian representations. While boosting the ReID accuracy, those operations introduce considerable computational overheads and make the deep models complex and hard to tune. To chase a more efficient solution, we propose a Part-Guided Representation (PGR) composed of Pose Invariant Feature (PIF) and Local Descriptive Feature (LDF), respectively. We call PGR "Part-Guided" because it is trained and supervised by local part cues. Specifically, PIF approximates a pose invariant representation inferred by pose estimation and pose normalization. LDF focuses on discriminative body parts by approximating a representation learned with body region segmentation. In this way, extra pose extraction is only introduced during the training stage to supervise the learning of PGR, but is not required during the testing stage for feature extraction. Extensive comparisons with recent works on five widely used datasets demonstrate the competitive accuracy and efficiency of PGR.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA