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1.
Carbohydr Polym ; 231: 115652, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888820

RESUMO

Hyaluronan (HA) have been widely used as the ideal biomaterials. It is important to understand their degradation and distribution for better optimization. From a new aspect of using radiotracers, we designed the HA-tyramine-bisphosphonate derivative for dual-labelling with two radionuclides (99mTc and 131I) simultaneously for in vitro and in vivo tracking. This dual-radiolabelled HA derivative can still be non-covalently crosslinked by hydroxyapatites to form injectable gel. The excellent properties of the gel, such as robust, biodegradable, and self-healing capacity were maintained. We firstly proved the possibility to distinguish different radionuclides in the degraded gel using the high-resolution gamma-ray spectrometry. The radiolabelled gel showed lower toxicity than pure hydroxyapatites against various cell lines, while the in vivo results proved that the 99mTc/131I-labelling of the gel was safe and stable enough for imaging and quantitatively tracking. The present method can also be applied for the development of dual-radiolabelled gels from other polysaccharides.

2.
Nat Commun ; 11(1): 35, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911623

RESUMO

The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. Here we show that TGF-ß signaling programs the development of ILC2s from their progenitors. Specifically, the deficiency of TGF-ß receptor II in bone marrow progenitors results in inefficient development of ILC2s, but not ILC1s or ILC3s. Mechanistically, TGF-ß signaling is required for the generation and maintenance of ILC2 progenitors (ILC2p). In addition, TGF-ß upregulates the expression of the IL-33 receptor gene Il1rl1 (encoding IL-1 receptor-like 1, also known as ST2) in ILC2p and common helper-like innate lymphoid progenitors (CHILP), at least partially through the MEK-dependent pathway. These findings identify a function of TGF-ß in the development of ILC2s from their progenitors.

3.
Chem Commun (Camb) ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31912820

RESUMO

A novel ratiometric surface-enhanced Raman scattering (SERS) biosensor was constructed based on stimuli-responsive DNA functionalized metal organic frameworks (MOFs) for detection of adenosine triphosphate (ATP). As a result, the detection range of ATP was 1 nM to 200 nM with a detection limit of 0.4 nM. The ratiometric SERS biosensor strategy offers a lower detection limit and exhibits a more enhanced performance than the typical SERS detection based on single signal response, which may have potential for detection of other biomolecules or metal ions.

4.
J Immunol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915260

RESUMO

IL-1R-associated kinases (IRAK) are important regulators in the TLR/IL-1R pathways, but their function appears inconsistent between Drosophila, bony fishes, and vertebrates. This causes a difficulty to understand the IRAK functions. As a step to reveal the evolution of IRAKs, in this study, we performed comparative and functional analysis of IRAKs by exploiting the amphioxus, a pivotal taxon connecting invertebrates and vertebrates. Sequence and phylogenetic analysis indicated three major IRAK lineages: IRAK1/2/3 is a vertebrate-specific lineage, IRAK4 is an ancient lineage conserved between invertebrate and vertebrates, and Pelle is another ancient lineage that is preserved in protostomes and invertebrate deuterostomes but lost in vertebrate deuterostomes. Pelle is closer neither to IRAK4 nor to IRAK1/2/3, hence suggesting no clear functional analogs to IRAK1/2/3 in nonvertebrates. Functional analysis showed that both amphioxus IRAK4 and Pelle could suppress NF-κB activation induced by MyD88 and TRAF6, which are unlike mammalian and Drosophila IRAKs, but, surprisingly, similar to bony fish IRAK4. Also unlike Drosophila IRAKs, no interaction was detected between amphioxus IRAK4 and Pelle, although both of them were shown capable of binding MyD88. These findings, together with previous reports, show that unlike other signal transducers in the TLR/IL-1R pathways, such as MyD88 and TRAF6, the functions of IRAKs are highly variable during evolution and very specialized in different major animal taxa. Indeed, we suggest that the functional variability of IRAKs might confer plasticity to the signal transduction of the TLR/IL-1R pathways, which in return helps the species to evolve against the pathogens.

5.
Micromachines (Basel) ; 10(12)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835484

RESUMO

Wearable sensing technologies have been developed rapidly in the last decades for physiological and biomechanical signal monitoring. Much attention has been paid to functions of wearable applications, but comfort parameters have been overlooked. This research presents a developed fabric temperature sensor by adopting fiber Bragg grating (FBG) sensors and processing via a textile platform. This FBG-based quasi-distributed sensing system demonstrated a sensitivity of 10.61 ± 0.08 pm/°C with high stability in various temperature environments. No obvious wavelength shift occurred under the curvatures varying from 0 to 50.48 m-1 and in different integration methods with textiles. The temperature distribution monitored by the developed textile sensor in a complex environment with multiple heat sources was deduced using MATLAB to present a real-time dynamic temperature distribution in the wearing environment. This novel fabric temperature sensor shows high sensitivity, stability, and usability with comfort textile properties that are of great potential in wearable applications.

6.
Onco Targets Ther ; 12: 9827-9848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819482

RESUMO

Introduction: MIR22HG has a reported involvement in the tumorigenesis of a variety of cancers, including hepatocellular carcinoma (HCC). However, the exact molecular mechanism of MIR22HG in HCC has not been clarified. Methods: In the present study, we integrated data from in-house RT-qPCR, RNA-sequencing, microarray, and literature studies to conduct a comprehensive evaluation of the clinico-pathological and prognostic significance of MIR22HG in an extremely large group of HCC samples. We also explored the potential mechanism of MIR22HG in HCC by analyzing the alteration profiles of MIR22HG in HCC to predict transcription factors (TFs) that may interact with MIR22HG and to annotate the biological functions of genes co-expressed with MIR22HG. MIR22HG expression was also compared in HCC nude mice xenografts before and after a treatment with nitidine chloride. Results: We found that MIR22HG was downregulated in HCC and that this downregulation correlated with the malignant phenotype of HCC. Comprehensive analysis of the prognostic impact of MIR22HG in HCC revealed a beneficial effect of MIR22HG on the survival outcome of HCC patients. Seven cases of MIR22HG deep deletion occurred in 360 of the cancer genome atlas (TCGA) provisional HCC samples. A total of 22 MIR22HG-TF-mRNA triplets in HCC were predicted by the lncRNAmap. Co-expressed genes of MIR22HG, identified by weighted correlation network analysis (WGCNA), mainly participated in the pathways involving osteoclast differentiation, chemokine signaling pathways, and hematopoietic cell lineage. In vivo experiments demonstrated that nitidine chloride could stimulate MIR22HG expression in HCC xenografts. Conclusion: In summary, MIR22HG may play a tumor-suppressive role in HCC by coordinating with predicted TFs and co-expressed genes, such as NLRP3, CSF1R, SIGLEC10, and ZEB2, or by being controlled by nitidine chloride.

7.
Fish Shellfish Immunol ; 97: 540-553, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31881329

RESUMO

This study investigated the effects of dietary curcumin on growth performance, non-specific immunity, antioxidant capacity and related genes expression of NF-κB and Nrf2 signaling pathways in grass carp (Ctenopharyngodon idella). A total of 525 juvenile grass carps with mean initial body weight of (5.30 ± 0.10) g were randomly distributed into five groups with three replicates each, fed five diets containing graded levels of curcumin (0, 196.11, 393.67, 591.46 and 788.52 mg/kg diet) for 60 days. After feeding trial, fifteen fish per tank were challenged with Aeromonas hydrophila and the mortalities were recorded for 7 days. The results showed that optimal dietary curcumin (393.67 mg/kg diet) improved the weight gain (WG) and specific growth rate (SGR) of juvenile grass carp, reduced feed conversion ratio (FCR) and the mortalities after challenge (P < 0.05). Moreover, optimal dietary curcumin increased the activities of lysozyme (LYZ) and acid phosphatase (ACP), and complement 3 (C3) and C4 levels, decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum of grass carp after injection with A. hydrophila (P < 0.05). Meanwhile, optimal dietary curcumin up-regulated the mRNA levels of LYZ, C3 and antimicrobial peptides [hepcidin, liver-expressed antimicrobial peptide-2 (LEAP-2), ß-defensin], and anti-inflammatory cytokines of interleukin-10 (IL-10) and transforming growth factor ß1 (TGF-ß1), and inhibitor of κBα (IκBα), whereas down-regulated pro-inflammatory cytokines of tumor necrosis factor-α (TNF-α), IL-1ß, IL-6 and IL-8, and nuclear factor kappa B p65 (NF-κB p65), IκB kinases (IKKα, IKKß and IKKγ) mRNA levels in the liver and blood of grass carp after injection with A. hydrophila (P < 0.05). In addition, optimal dietary curcumin increased the reduced glutathione (GSH) content and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR), reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the liver of grass carp after injection with A. hydrophila (P < 0.05). Meanwhile, optimal dietary curcumin up-regulated the mRNA levels of these antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2), whereas down-regulated Kelch-like ECH-associated protein (Keap) 1a and Keap 1b mRNA levels (P < 0.05) in the liver and blood of grass carp after injection with A. hydrophila. Thus, optimal dietary curcumin supplementation could promote growth of juvenile grass carp, reduce FCR, and enhance disease resistance, innate immunity and antioxidant capacity of fish, attenuating inflammatory response. However, dietary excessive curcumin had negative effect on fish. Based on second-order regression analysis between dietary curcumin contents and weight gain, the optimum requirement of dietary curcumin in juvenile grass carp was determined to be 438.20 mg/kg diet.

8.
Exp Parasitol ; 209: 107827, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31877276

RESUMO

Perkinsus olseni is a widely distributed protozoan pathogen that infects a wide range of marine mollusks. Prezoosporulation of P. olseni trophozoites is easily observed in Ray's fluid thioglycollate medium, but in nature, trophozoites within host tissue should be able to develop into prezoosporangia without any additional artificial medium after the host dies. How this process might work in field conditions remains poorly understood, however, partly because of the lack of appropriate in vitro assays. In this study, we observed that trophozoites of P. olseni successfully developed into prezoosporangia when mixed with minced tissue of the Manila clam Ruditapes philippinarum and placed in seawater. We were thus able to establish a new method to examine the development of P. olseni to prezoosporangia under artificially simulated natural environmental conditions. Using this method, we found that low temperatures (5 °C, 15 °C) significantly suppressed prezoosporangia development. In addition, we found that prezoosporangia were developed in a wide range of salinities (10-50 practical salinity unit) and that P. olseni requires some nutrition factors from host tissue for prezoosporulation to occur. Because the transmission of P. olseni among a host population highly depends on the developmental process of prezoosporangia, which leads to production of the infective zoospore stage, these results will help further our understanding of the parasite's infection dynamics in nature.

9.
Endocr Relat Cancer ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705798

RESUMO

Sorafenib, a small molecule tyrosine kinase inhibitor with antiangiogenic activity, has been used in liver cancer and kidney cancer treatment. However, clinical trials with sorafenib for breast cancer were stopped in phase Ⅲ due to limited efficacy. The existence of heterogeneous vasculatures involving tumor cells, such as vessel-like structures formed by vasculogenic mimicry and mosaic vessels, and their resistance to antiangiogenic therapy are thought to be a possible reason for failure of sorafenib therapy. Nevertheless, the features and mechanism of vasculogenesis by tumor cells remain unclear. In the present study, we found that breast cancer stem-like cells (BCSLCs, ALDH1+ cells) were involved in vasculogenic mimicry and mosaic vessel formation in triple-negative breast cancer tissues. Further, only ALDH1+ BCSLCs sorted from MDA-MB-231 could exhibit the tube formation and angiogenesis ability. Sorafenib could inhibit vascularization from endothelial cells rather than that from ALDH1+ cells. α-SMA was identified as a key molecule in vascular formation of BCSLCs. Mechanistically, HIF-1α enhanced the mRNA and protein levels of α-SMA by binding to the HRE element in the promoter directly and meanwhile increased the BCSLCs population. Interestingly, pigment epithelium-derived factor (PEDF), an endogenous angiogenesis inhibitor, could inhibit both endothelial cell-derived and tumor cell-derived angiogenesis by down-regulating HIF-1α in breast cancer. Our finding clarified the possible reason for the poor outcome of anti-angiogenesis therapy and PEDF may have the therapeutic potential.

10.
Mol Oncol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670863

RESUMO

Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), a key regulator of DNA double-strand break repair and recombination, is downregulated in HCC tissues and suppresses tumor growth. In clinical HCC samples, low expression of RDM1 correlates with larger tumor size, poor tumor differentiation and unfavorable survival. In vitro and in vivo data demonstrate that knockdown of RDM1 increases HCC cell proliferation, colony formation and cell population at G2/M phase, whereas RDM1 overexpression results in the opposite phenotypes. Mechanistically, RDM1 binds to the tumor suppressor p53 and enhances its protein stability. In the presence of p53, RDM1 suppresses the phosphorylation of Raf and ERK. Overexpression of p53 or treatment with ERK inhibitor significantly abolishes cell proliferation induced by the depletion of RDM1. In addition, overexpression of methyltransferase-like 3 (METTL3) markedly induces N6-methyladenosine (m6 A) modification of RDM1 mRNA and represses its expression. Taken together, our study indicates that RDM1 functions as a tumor suppressor and may be a potential prognostic and therapeutic factor for HCC.

11.
J Cell Mol Med ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769590

RESUMO

High-mobility group box 1 (HMGB1) shows pro-inflammatory activity in various inflammatory diseases and has been found up-regulated in chronic obstructive pulmonary disease (COPD). Lung macrophages play an important role in airway inflammation and lung destruction in COPD, yet whether HMGB1 is involved in cigarette smoke (CS)-induced lung macrophage dysfunction is unknown. We sought to evaluate the intracellular localization and release of HMGB1 in lung macrophages from COPD patients and CS-exposed mice, and to investigate the role of HMGB1 in regulating autophagy in CS extract (CSE)-treated lung macrophages (MH-S cells). Our results showed that HMGB1 was highly expressed in lung tissues and sera of COPD patients and CS-exposed mice, along with predominantly cytoplasmic exporting from nuclei in lung macrophages. In vitro experiments revealed that CSE promoted the expression, nucleocytoplasmic translocation and release of HMGB1 partly via the nicotinic acetylcholine receptor (nAChR). Blockade of HMGB1 with chicken anti-HMGB1 polyclonal antibody (anti-HMGB1) or glycyrrhizin (Gly) attenuated the increase of LC3B-II and Beclin1, migration and p65 phosphorylation, suggesting the involvement of HMGB1 in autophagy, migration and NF-κB activation of lung macrophages. Hydroxychloroquine (CQ), an autophagy inhibitor, enhanced the increase of LC3B-II but not Beclin1 in CSE or rHMGB1-treated MH-S cells, and inhibition of autophagy by CQ and 3-methyladenine (3-MA) abrogated the migration and p65 phosphorylation of CSE-treated cells. These results indicate that CS-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages, providing novel evidence for HMGB1 as a potential target of intervention in COPD.

12.
Genes (Basel) ; 10(12)2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31771247

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition of the liver encompassing a range of pathologies including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Research into this disease is imperative due to its rapid growth in prevalence, economic burden, and current lack of FDA approved therapies. NAFLD involves a highly complex etiology that calls for multi-tissue multi-omics network approaches to uncover the pathogenic genes and processes, diagnostic biomarkers, and potential therapeutic strategies. In this review, we first present a basic overview of disease pathogenesis, risk factors, and remaining knowledge gaps, followed by discussions of the need and concepts of multi-tissue multi-omics approaches, various network methodologies and application examples in NAFLD research. We highlight the findings that have been uncovered thus far including novel biomarkers, genes, and biological pathways involved in different stages of NAFLD, molecular connections between NAFLD and its comorbidities, mechanisms underpinning sex differences, and druggable targets. Lastly, we outline the future directions of implementing network approaches to further improve our understanding of NAFLD in order to guide diagnosis and therapeutics.

13.
J Clin Lab Anal ; : e23129, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774215

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized as glucose intolerance of any degree that begins or first diagnosed during pregnancy. It possesses a higher risk of haemorrhage, which may be caused by the coagulation dysfunction. However, there has been no study focus on how coagulation state changes in the progress of GDM pregnancy. Our study is aimed to assess the association of coagulation function and haemorrhage in GDM. METHODS: A total of 662 subjects (273 from a population-based study and 389 from a prospective cohort study) were selected to measure mean platelet volume (MPV), platelet distribution width (PDW), platelet (PLT), thrombocytocrit (PCT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). All pregnant individuals were divided into normal glucose tolerance (NGT) controls and GDM patients diagnosed between the 24th and 28th weeks of gestation. RESULTS: Compared with NGT controls, GDM females showed shortened PT, shortened APTT, and increased blood FIB levels, while the platelet parameters MPV, PDW, PLT, and PCT remained unchanged in mid-pregnancy. By late pregnancy, the platelet parameters MPV, PDW, and PCT were increased in the GDM group compared with the NGT group, while PT and APTT were unchanged. CONCLUSIONS: The GDM group was hypercoagulable compared with the NGT group rather than hypocoagulable as predicted, but still within the normal range. Therefore, our findings demonstrate that the variation degree of coagulation function is not responsible for extra risk of hemorrhage in GDM, and prevention of hemorrhage should focus on other causes.

14.
J Vet Sci ; 20(6): e68, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31775195

RESUMO

Viral-encoded microRNAs (miRNAs) have vital roles in the regulation of virus replications and host immune responses. The results of previous studies have indicated that miRNA clusters are involved in the replication and virulence of the pseudorabies virus (PRV), which may potentially lead to immune escape or facilitation of PRV replication. This study's previous research revealed that prv-miR-LLT11a was differentially expressed during PRV infection. The present study's results have demonstrated that prv-miR-LLT11a could significantly inhibit PRV replication. It was further determined that SLA-1 was the target gene of prv-miR-LLT11a, and simultaneously, that overexpression of prv-miR-LLT11a could downregulate the mRNA and protein levels of SLA-1 in a dose-independent manner. Furthermore, the present study also observed that prv-miR-LLT11a can downregulate TAP1 expression. Our findings provide a better understanding of the molecular mechanism involved in the effects of prv-miR-LLT11a on SLA-1 and TAP1 as well as its involvement in immune system evasion of PRV.

15.
Curr Drug Metab ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31749422

RESUMO

BACKGROUND: Exosomes are small extracellular vesicles (EVs) (40-100nm) secreted by living cells and mediate the transmission of information between cells. The number and contents of exosomes are associated with diseases such as inflammatory diseases, cancer, metabolic diseases and what we are focusing in this passage. OBJECTIVE: This review focused on the role of exosomes in oocyte development, declined ovarian function, PCOS, uterine diseases, endometrial receptivity and fallopian tube dysfunction in the female. METHODS: We conducted an extensive search for research articles involving relationships between exosomes and female infertility on bibliographic database. RESULTS: It's reported that exosomes can act as a potential therapeutic device to carry cargoes to treat female infertility. However, the pathophysiological mechanism of exosomes in female infertility has not been entirely elucidated. Further researches are needed to explore the etiology and provide evidence for potential clinical treatment. CONCLUSIONS: This review systematically summarized the role exosomes play in female infertility and its potential as drug delivery.

16.
Chem Commun (Camb) ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750461

RESUMO

A triple sequential junction by rationally combining anatase/rutile nanoparticle TiO2 heterophase (Ans/R) and rutile/rutile TiO2 homophase (Rns/R) junctions was fabricated as a proof of concept. Such a continuous charge separation and transfer channel resulted in a remarkable enhancement in the separation of photogenerated carriers and the photocatalytic activity.

17.
Res Microbiol ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31676435

RESUMO

The type VI secretion system (T6SS), a multifunctional protein secretion device, plays very important roles in bacterial killing and/or virulence to eukaryotic cells. Although T6SS genes have been found in many Xanthomonas species, the biological function of T6SSs has not been elucidated in most xanthomonads. In this study, we identified two phylogenetically distinct T6SS clusters, T6SS1 and T6SS2, in a newly sequenced Chinese strain GX01 of Xanthomonas oryzea pv. oryzicola (Xoc) which causes bacterial leaf streak (BLS) of rice (Oryza sativa L.). Mutational assays demonstrated that T6SS1 and T6SS2 are not required for the virulence of Xoc GX01 on rice. Nevertheless, we found that T6SS2, but not T6SS1, played an important role in bacterial killing. Transcription and secretion analysis revealed that hcp2 gene is actively expressed and that Hcp2 protein is secreted via T6SS. Moreover, several candidate T6SS effectors were predicted by bioinformatics analysis that might play a role in the antibacterial activity of Xoc. This is the first report to investigate the type VI secretion system in Xanthomonas oryzae. We speculate that Xoc T6SS2 might play an important role in inter-bacterial competition, allowing this plant pathogen to gain niche advantage by killing other bacteria.

18.
Thorac Cancer ; 10(12): 2236-2242, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31679181

RESUMO

BACKGROUND: Previous studies have documented the therapeutic value of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for early-stage non-small cell lung cancer (NSCLC). However, few studies have focused on patients aged 80 years and older. This retrospective study aimed to evaluate the safety and clinical outcomes of CT-guided percutaneous MWA in patients aged 80 years and older with early-stage peripheral NSCLC. METHODS: A retrospective analysis of 63 patients aged 80 years and older with cT1a-2bN0M0 peripheral NSCLC who underwent CT-guided percutaneous MWA was performed between January 2008 and January 2018 at 11 hospitals in Shandong Province, China. RESULTS: The median follow-up time was 21.0 months. The overall median survival time was 50 months. The cancer-specific median survival time was not reached in five years. The one-, two-, three-, four-, and five-year overall survival rates were 97.1%, 92.6%, 63.4%, 54.4%, and 32.6%, respectively. The one-, two-, and three-year cancer-specific survival (CSS) rates were 97.9%, 97.9%, and 69.4%, respectively. The four- and five-year CSS rates were not achieved. A total of 14 patients (22.2%) had local progression. The one-, two-, three-, four-, and five-year local control rates were 88.8%, 78.8%, 70.3%, 63.9%, and 63.9%, respectively. The mortality rate was 0% within 30 days after the procedure. Major complications included pneumothorax requiring drainage (21.1%), pulmonary infection (4.2%), and pleural effusions requiring drainage (2.8%). CONCLUSIONS: CT-guided percutaneous MWA is a safe and effective modality for treating patients aged 80 years and older with early-stage peripheral NSCLC.

19.
Transl Lung Cancer Res ; 8(5): 636-648, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31737499

RESUMO

Background: Our previous studies have identified a serum-based 4-microRNA (4-miRNA) signature that may help distinguish patients with lung cancer (LC) from non-cancer controls (NCs). Here, we used an extended independent cohort of 398 subjects to further validate the diagnostic ability of this 4-miRNA signature. Methods: Using quantitative reverse transcription polymerase chain reaction (qRT-PCR), expression of the 4-miRNAs was assessed in a total of 398 sera that included 213 LC patients and 185 NCs. A logistic regression model using training-test sets, receiver operating characteristic (ROC) curve analysis and t-test were used to test the impact of varying expression of these miRNAs on its diagnostic accuracy for LC. The cell proliferation and colony formation affected by these miRNAs, as well as gene ontology (GO) analysis of miRNA target genes were performed. Results: The levels of the 4-miRNAs were significantly higher in the serum of patients with LCs as compared to NCs. Using a logistic regression prediction model based on training and test sets analysis, we obtained the area under the curve (AUC) of 0.921 [95% confidence interval (CI), 0.876-0.966] on the test set with specificity 90.6%, sensitivity 77.9%, accuracy 84.1%, positive predictive value (PPV) 89.8% and negative predictive value (NPV) 79.5%. Conclusions: We have verified that this serum 4-miRNA signature could provide a promising noninvasive biomarker for the prediction of LC, particularly in patients with indeterminate lung nodules on screening CT scans.

20.
Clin Chim Acta ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31758933

RESUMO

BACKGROUND: The value of urinary mitochondrial DNA (mtDNA) for assessing kidney injury of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was investigated. METHODS: Thirty-nine kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients were enrolled and analyzed. RESULTS: The average urinary mtDNA of patients was significantly higher than that of normal controls (3372.74 ± 1859.72 vs. 474.90 ± 123.59 copy/nmol creatinine, p < 0.001). The patients who needed dialysis at disease onset had the highest levels of urinary mtDNA (5072.23 ± 1302.87 copy/nmol creatinine). Urinary mtDNA positively correlated with urinary neutrophil gelatinase-associated lipocalin (R = 0.661, P < 0.001) and negatively correlated with estimated glomerular filtration rate (R = -0.515, P = 0.001). The urinary mtDNA level of crescentic class (4703.08 ± 1744.31 copy/nmol creatinine) was higher than that of mixed class (3258.14 ± 1158.99 copy/nmol creatinine) and focal class (2268.15 ± 1897.63 copy/nmol creatinine). Univariate correlation analysis showed urinary mtDNA positively correlated with interstitial neutrophils (R = 0.471, P = 0.048) and glomerular neutrophils (R = 0.673, P = 0.002) in kidney biopsy. Among 13 patients who needed hemodialysis at disease onset, 10 patients who got renal recovery had higher urinary mtDNA than 3 patients who remained dialysis dependent (5455.20 ± 1174.64 vs. 3795.67 ± 893.34 copy/nmol creatinine, p = 0.047). CONCLUSIONS: Urinary mtDNA increases in AAV with kidney injury, and its levels correlate with the severity of kidney injury and neutrophils infiltration in pathology.

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