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1.
Drug Discov Today ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33524602

RESUMO

Scars affect millions of patients worldwide, yet their treatment efficacy and options clinically remain limited. In recent years, increased understanding of scar formation pathways leading to developments in nanotechnology have opened many opportunities for scar detection, prevention, and treatment due to the nanoscale features and therapeutic delivery capabilities of such technologies. Led by nanoparticles (NPs) and nanofibers, these novel strategies can aid in reducing scar contracture, improving wound-healing efficacy, and advancing progress towards scarless wound healing.

2.
Nano Lett ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591201

RESUMO

Small extracellular vesicles (sEVs) are increasingly recognized as noninvasive diagnostic markers for many diseases. Hence, it is highly desirable to isolate sEVs rapidly for downstream molecular analyses. However, conventional methods for sEV isolation (such as ultracentrifugation and immune-based isolation) are time-consuming and expensive and require large sample volumes. Herein, we developed artificial magnetic colloid antibodies (MCAs) via surface imprinting technology for rapid isolation and analysis of sEVs. This approach enabled the rapid, purification-free, and low-cost isolation of sEVs based on size and shape recognition. The MCAs presented a higher capture yield in 20 min with more than 3-fold enrichment of sEVs compared with the ultracentrifugation method in 4 h. Moreover, the MCAs also proposed a reusability benefiting from the high stability of the organosilica recognition layer. By combining with volumetric bar-chart chip technology, this work provides a sensitive, rapid, and easy-to-use sEV detection platform for point-of-care (POC) diagnostics.

3.
Aging (Albany NY) ; 13(3): 3866-3885, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33461166

RESUMO

Long non-coding RNAs (lncRNA) play a vital role in colorectal cancer (CRC) progression. To investigate the role of long intergenic non-coding RNA LINC00485 in CRC, we performed in vitro functional experiments. LoVo tumor-bearing and liver metastasis mice were used as in vivo models. We found that LINC00485 expression was significantly lower in CRC tissues and cancer cells than in paired normal samples and human normal colonic epithelial cells. Lower expression of LINC00485 predicted poor prognosis in CRC patients. LINC00485 knockdown promoted the proliferation, migration, and invasion of FHC cells, while LINC00485 overexpression weakened these abilities of LoVo cells. MicroRNA miR-581 was the downstream target of LINC00485, which was downregulated in CRC samples and cancer cells compared to normal tissues and normal colonic epithelial cells. MiR-581 overexpression induced proliferation, migration, and invasion of FHC cells, while miR-581 antagomir treatment produced opposite results. MiR-581 directly targeted the 3'UTR of EDEM1 and inhibited its expression and induction of epithelial-mesenchymal transition of CRC. In mouse models, LINC00485 knockdown or down-regulation of miR-581 significantly repressed CRC cell growth and prevented CRC liver metastasis. Overall, LINC00485 suppressed CRC tumorigenesis and progression by targeting the miR-581/EDEM1 axis. LINC00485 may be a potential therapeutic target for CRC.

4.
Biosci Rep ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33289788

RESUMO

MicroRNA-196a (miR-196a) was previously reported to be upregulated in cancers, and it has the diagnostic and prognostic values in cancers. Whereas, the conclusion was still unclear according to the published data. To assess such roles of miR-196a in cancers, this study was conducted based on published data and online cancer related databases. To identify the relevant published data, we searched articles in databases and then the relevant data was extracted to evaluate the correlation between miR-196a expression and diagnosis, prognosis for cancer patients. The pooled results showed that miR-196a was a valuable diagnostic biomarker in cancer (AUC=0.87, 95%CI: 0.84-0.90; sensitivity=0.73, 95%CI:0.64-0.81; specificity=0.90, 95%CI:0.81-0.95), which was consistent with the data from databases (breast cancer: miR-196a-3p: AUC=0.77, 95%CI: 0.74-0.79; miR-196a-5p: AUC=0.71, 95%CI: 0.66-0.75; pancreatic cancer: miR-196a-3p: AUC=0.80, 95%CI: 0.73-0.87; miR-196a-5p: AUC=0.61, 95%CI:0.51-0.71). In addition, the pooled result revealed that elevated miR-196a expression in tissues (HR=2.54, 95%CI: 1.79-3.61, PHeterogeneity =0.000, I2=75.8%) or serum/plasma (HR=4.06, 95%CI: 2.67-6.18, PHeterogeneity =0.668, I2=0%) was an unfavorable survival biomarker, which was consistent with the data from databases (adrenocortical carcinoma: HR=5.70; esophageal carcinoma: HR=1.93; brain lower grade glioma: HR=2.91; GSE40267: HR=2.47, 95%CI: 1.2-5.07; TCGA: HR=1.82, 95%CI: 1.21-2.74; GSE19783: HR=4.24, 95%CI:1-18.06). In short, our results demonstrated that miR-196a in tumor tissue or serum/plasma could be used as a prognostic and diagnostic values for cancers.

5.
Ann Palliat Med ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33353349

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to grow worldwide, and systematic reviews (SRs)/meta-analyses (MAs) on COVID-19 can efficiently guide evidence-based clinical practice. However, SRs/MAs with weaknesses can mislead clinical practice and pose harm to patients, and too many useless SRs/MAs could pose confusion and waste sources. A "living" overview of SRs/MAs aims to provide an open, accessible and frequently updated resource summarizing the highest-level evidence of COVID-19, that can help evidence-users to quickly identify trusted evidence to guide the practice. This study aims to systematically give an overview SRs/MAs of COVID-19, assess their quality, and identify the best synthesis of evidence. METHODS: Databases including Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) and WanFang were systematically searched on May 1, 2020 using relevant terms for identify SRs/MAs related to COVID-19. The study selection, data extraction and quality assessment will be performed by independent reviewers, and results will be crosschecked. The authoritative tools (AMSTAR-2, PRISMA and its extensions) will be used to assess the methodological quality and reporting quality of included SRs/MAs, and potential influence factors will be explored. The consistency of conclusions will be compared among reviews and the best evidence will be summarized. In addition, we will conduct exploratory meta-analyses (MAs) of individual studies when applicable. Data will be reported as number with (or) percentage, risk ratio (RR) or odds ratio (OR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) according to the specific results. R3.6.1 and Microsoft Excel 2016 will be used to analyze and manage data. RESULTS: The results of this overview will be submitted to a peer-reviewed journal for publication. DISCUSSION: In this study, we will present for the first time, an overview of SRs/MAs, which provides a comprehensive, dynamic evidence landscape on prevalence, prevention, diagnosis, treatment, and prognosis of COVID-19.

6.
Psychol Health Med ; : 1-12, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33315480

RESUMO

To assess and compare the QoL of the older people dwelling in traditional family versus nursing home/institution. A comprehensive literature search was performed on 10 January 2018 to identify studies that investigated the QoL of older adults dwelling in family versus nursing home settings. Analyses were run using random-effects meta-analyses. A total of six cross-sectional studies with 1623 people were included. The quality of included studies was moderate. Meta-analysis showed that compared with nursing home support, the family support could significantly improve the physical health (6 studies, SMD = 0.50, 95%CI: 0.32-0.68, p < 0.05), mental status (6 studies, SMD = 0.45, 95%CI: 0.26-0.65, p < 0.05), and social relationship (5 studies, SMD = 0.51, 95%CI: 0.19-0.83, p < 0.05). Traditional family support model demonstrated a significant improvement in the physical health, psychological status and social relationships among older adults. The conclusions were driven by cross-sectional studies, Larger, adequately powered RCTs are required to confirm our finding.

7.
Mol Ther Nucleic Acids ; 22: 750-765, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230473

RESUMO

Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancer-related deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both in vitro and in vivo. Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/ß-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC.

8.
Aging (Albany NY) ; 12(21): 21638-21659, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159022

RESUMO

N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of messenger RNAs (mRNAs) and catalyzed by a multicomponent methyltransferase complex (MTC), among which methyltransferase-like 3 (METTL3) and METTL14 are two core molecules. However, METTL3 and METTL14 play opposite regulatory roles in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, we conducted a multi-omics analysis of METTL3 and METTL14 in HCC, including RNA-sequencing, m6ARIP-sequencing, and ribosome-sequencing profiles. We found that the expression and prognostic value of METTL3 and METTL14 are opposite in HCC. Besides, after METTL3 and METTL14 knockdown, most of the dysregulated mRNAs, signaling pathways and biological processes are distinct in HCC, which partly explains the contrary regulatory role of METTL3 and METTL14. Intriguingly, these mRNAs whose stability or translation efficiency are influenced by METTL3 or METTL14 in an m6A dependent manner, jointly regulate multiple signaling pathways and biological processes, which supports the cooperative role of METTL3 and METTL14 in catalyzing m6A modification. In conclusion, our study further clarified the contradictory role of METTL3 and METTL14 in HCC.

9.
Pharmgenomics Pers Med ; 13: 563-570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154659

RESUMO

Background: Paraoxonases (PONs) are a family of orphan enzymes with multiple functions, including anti-inflammatory, antioxidative, antiatherogenic activities. Studies have suggested that genetic variations in PON1 and PON2 are associated with ischemic stroke (IS) risk; however, the conclusion remains unclear in the Chinese population. Methods: To investigate the susceptibility of genetic variations in PON1 and PON2 to risk of IS and its subtypes, this case-control study was carried out on a Chinese population comprising 300 IS patients and 300 healthy controls. Genotypes of six genetic variations in PON1 and PON2 were identified with an improved multiplex ligase detection-reaction technique. Results: PON1 rs662 was associated with increased risk of IS (CT vs. TT - ORadjusted 1.79, 95% CI 1.08-2.97; p=0.025). Stratified analysis for patients by sex revealed that the significant association of PON1 rs662 with IS risk was maintained in the male cohort (CT vs. TT - ORadjusted 2.59, 95% CI 1.29-5.21 [p=0.009]; CT/CC vs. TT - ORadjusted 2.03, 95% CI 1.05-3.93 [p=0.036]), but not in the female cohort. Analysis according to IS subtype revealed that PON1 rs662 genetic variation was an increased risk in the subcohort of patients with large-artery atherosclerosis (CT/CC vs. TT - ORadjusted 2.31, 95% CI 1.09-4.91; p=0.029), but not in patients with other types of IS. Conclusion: This study suggested that PON1 rs662 presented a potential risk of IS, especially for males, and this association was more obvious for large-artery atherosclerosis.

10.
Pathol Res Pract ; 217: 153268, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33246290

RESUMO

BACKGROUND: A growing number of studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of tumors. In this study, we explored the function and molecular mechanism of lncRNA SPINT1-AS1 in breast cancer progression. METHODS: A total of 30 patients and 25 healthy controls were enrolled to detect the expression of SPINT1-AS1 in the serum by RT-qPCR. CCK-8 assay, clone formation assay, EdU assay, Transwell assay, Flow cytometry for apoptosis assay and wound healing assays were used to explore the effects of SPINT1-AS1 on the proliferation and migration of breast cancer cells. Bioinformatics analysis were used to enrich the downstream target genes and related pathways of miRNAs interacting with SPINT1-AS1, construct a competitive endogenous RNA (ceRNA) network diagram. RESULTS: SPINT1-AS1 is up-regulated in the serum of breast cancer patients and breast cancer cell lines. The proliferation and migration ability of breast cancer cells were decreased significantly after SPINT1-AS1 knockdown, and it may inhibit its expression by sponging miR-let-7a/b/i-5p, thereby promoting breast cancer progression. CONCLUSIONS: SPINT1-AS1 can promote the proliferation and migration of breast cancer cells by regulating miR-let-7a/b/i-5p, suggesting that it may be an important regulator of breast cancer progression.

11.
Biomater Sci ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078786

RESUMO

Bacteria and cancer cells share a unique symbiotic relationship in the process of cancer development and treatment. It has been shown that certain bacteria can mediate cancer and thrive inside cancerous tissues. Moreover, during cancer treatment, microbial infections have been shown to impair the therapeutic efficacy and lead to serious complications. In the past decades, the application of antibiotics has achieved great success in fighting numerous bacteria but the administration route, low localization effects and related drug resistance limit the further utilization of antibiotics. Recently, advances in nanotechnology have made a significant impact in the medical field, which enhance the drug solubility and can target lesion sites, and some nanomaterials can even be applied as the therapeutic agent itself. In this review, we introduce anti-bacterial nanosystems for cancer therapy in the aspects of spontaneous and triggered anti-bacterial action, and our notions, as well as proposed research directions for the further development of this field, are discussed.

12.
Ecotoxicol Environ Saf ; 208: 111438, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33039873

RESUMO

Roles of environmental factors in transmission of COVID-19 have been highlighted. In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. Fifteen sites were sampled from the quarantine room, distributing in the functional areas such as bedroom, bathroom and living room. All environmental surface samples were collected with sterile polyester-tipped applicator pre-moistened in viral transport medium and tested for SARS-CoV-2. Overall, 34.1% of samples were detected positively for SARS-CoV-2. The positive rates of Patient A, B and C, were 46.2%, 0% and 61.5%, respectively. SARS-CoV-2 was detected positively in bedroom and bathroom, with the positive rate of 50.0% and 46.7%, respectively. In contrast, living room had no positive sample detected. Environmental contamination of SARS-CoV-2 distributes widely during the incubation period of COVID-19, and the positive rates of SARS-CoV-2 on environmental surfaces are relatively high in bathroom and bedroom.

13.
BMC Geriatr ; 20(1): 338, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907557

RESUMO

BACKGROUND: This study aims to analyse the current demand by senior citizens in Lanzhou, China for a combination of medical and elderly care services and to identify the factors influencing their needs. METHODS: 7500 participants aged 60 or above living in Lanzhou, China, were recruited, a unified questionnaire concerning elderly people's demand for a service combining medical and elderly care has been adopted to survey these subjects. The status quo of the demand of the service combining medical and elderly care and its influencing factors were analysed with the single-factor Chi-square test and multi-factor binomial logistic regression method. RESULTS: 3772 of 7320 older people have the demand for the service combining medical and elderly care, accounting for 53.15% of survey respondents. Many factors are in play, including gender, marital status, degree of education, occupation before retirement, number of children, monthly income, health self-assessment status, endowment insurance type, medical insurance type, current nursing arrangements, old-age demands, self-care ability and the knowledge of combining medical and elderly care and the willingness to pay for the combination of medical and elderly care have statistical significance (P < 0.05) with the elderly's needs, different ages, living styles and the prevalence of chronic diseases, have no statistical significance (P > 0.05) with the elderly's care needs in Lanzhou. The number of children, type of medical insurance and willingness to pay for the combination of medical treatment and nursing care are major influencing factors among the complex factors influencing the elderly's demand for the proposed service. CONCLUSIONS: The low knowledge rate and demand rate, the number of children, the type of medical insurance, and the willingness to pay for the medical-nursing combination service for the elderly in Lanzhou have a great impact on the elderly's demand rate for combining medical and elderly care. Meanwhile, relevant government departments should focus more on the promotion of the endowment model of combining medical and elderly care and provide integrated medical care services by integrating multiple resources, and improving social security.

14.
Front Pharmacol ; 11: 1186, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848789

RESUMO

Background: Several clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta­analysis with trial sequential analysis (TSA). Methods: We searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed. Results: Nine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02, P = 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52, P = 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57, P = 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13, P = 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32, P = 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94, P = 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08, P = 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06, P = 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84, P = 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required. Conclusions: Limited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32671029

RESUMO

Cardiovascular stenting is an effective method for treating cardiovascular diseases (CVDs), yet thrombosis and restenosis are the two major clinical complications that often lead to device failure. Nitric oxide (NO) has been proposed as a promising small molecule in improving the clinical performance of cardiovascular stents thanks to its anti-thrombosis and anti-restenosis ability, but its short half-life limits the full use of NO. To produce NO at lesion site with sufficient amount, NO-producing coatings (including NO-releasing and NO-generating coatings) are fashioned. Its releasing strategy is achieved by introducing exogenous NO storage materials like NO donors, while the generating strategy utilizes the in vivo substances such as S-nitrosothiols (RSNOs) to generate NO flux. NO-producing stents are particularly promising in future clinical use due to their ability to store NO resources or to generate large NO flux in a controlled and efficient manner. In this review, we first introduce NO-releasing and -generating coatings for prevention of thrombosis and restenosis. We then discuss the advantages and drawbacks on releasing and generating aspects, where possible further developments are suggested.

16.
Mol Cancer ; 19(1): 106, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552762

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide, and its main cause of death is distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, is involved in tumor progression via regulating RNA function. The goal of the study is to uncover the biological function and molecular mechanism of METTL14 in CRC. METHODS: Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were employed to detect METTL14 and SOX4 in CRC cell lines and tissues. The biological functions of METTL14 were demonstrated using in vitro and in vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic RNA sequencing (RNA-Seq), m6A-RNA immunoprecipitation sequencing (MeRIP-Seq), RNA immunoprecipitation and luciferase reporter assays were used to explore the mechanism of METTL14 action. RESULTS: METTL14 expression was significantly downregulated in CRC and decreased METTL14 was associated with poor overall survival (OS). Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation of histone H3 lysine 4 tri-methylation(H3K4me3) in the promoter of METTL14 inhibited METTL14 transcription. Functionally, we verified that METTL14 inhibited CRC cells migration, invasion and metastasis through in vitro and in vivo assays, respectively. Furthermore, we identified SRY-related high-mobility-group box 4(SOX4) as a target of METTL14-mediated m6A modification. Knockdown of METTL14 markedly abolished SOX4 mRNA m6A modification and elevated SOX4 mRNA expression. We also revealed that METTL14-mediated SOX4 mRNA degradation relied on the YTHDF2-dependent pathway. Lastly, we demonstrated that METTL14 might inhibit CRC malignant process partly through SOX4-mediated EMT process and PI3K/Akt signals. CONCLUSIONS: Decreased METTL14 facilitates tumor metastasis in CRC, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for CRC.

17.
Medicine (Baltimore) ; 99(20): e20079, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443317

RESUMO

INTRODUCTION: China is facing more and more enormous challenges including aging, the increase of social security costs and health care cost, decrease of labors, and how to keep elders' capacity to function well and live independently. Healthy aging has become an extremely challenging issue. Frailty, a geriatric syndrome resulted from the declines of multiple physiological systems, characterized by malnutrition, exercise intolerance, dependence, longer bed rest, lower gaits peed, weakness, weight loss, anorexia, hip fracture, risk of falling, delirium, dementia, and keep indoors, has become one of the biggest challenges in facilitating healthy aging. Because the research of frailty just had started in recent years in China, the evidence regarding the prevalence of frailty among the Chinese population is scarce and just limited in certain area. METHOD: We will systematically search 7 electronic database including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, MEDLINE, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) to identify studies that provide or potential available of data regarding to prevalence of frailty. Risk of bias of individual study will be assessed using 8-iterm critical appraisal criteria for prevalence or incidence studies. Data will be analyzed using STATA V.12.0 software. CONCLUSIONS: Our systematic review and meta-analysis will firstly pool the results from available studies to provide a comprehensive evidence for the prevalence of frailty. The results of this study will be submitted to a peer-reviewed journal for publication.


Assuntos
Fragilidade/epidemiologia , Metanálise como Assunto , Revisões Sistemáticas como Assunto , China/epidemiologia , Humanos , Prevalência
18.
Drug Discov Today ; 25(9): 1772, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32268202

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

19.
IUBMB Life ; 72(7): 1393-1403, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32107843

RESUMO

Metastasis is responsible for 90% of colorectal cancer (CRC)-related deaths. In the present study, we identified a novel key regulator of CRC metastasis, leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3), which was significantly decreased in CRC tissues and cell lines. Downregulation of LRIG3 was attributed to copy number loss and promoter hypermethylation. Low LRIG3 expression was positively correlated with metastatic clinical features and shorter survival time. Functional experiments showed that knockout of LRIG3 markedly enhanced CRC cell migration and invasion ability, whereas reintroduction of LRIG3 exerted the opposite effects. Regarding the mechanism, LRIG3 could facilitate the binding of DUSP6 to ERK1/2, resulting in the dephosphorylation of ERK1/2 and subsequently downregulation of slug, an epithelial-to-mesenchymal transition trigger, thereby constraining CRC cell motility. Importantly, LRIG3 expression was strongly negatively correlated with slug or p-ERK1/2 expression in CRC tissues. Collectively, our data suggest that LRIG3 is a novel suppressor of CRC metastasis, reactivation of LRIG3 may be a promising therapeutic approach for metastatic CRC patients.

20.
J Cancer ; 11(3): 630-637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31942186

RESUMO

Background: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM). Materials and methods: Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models. Results: After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni- and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients. Conclusions: Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.

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