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1.
Lung Cancer ; 150: 36-43, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33059150

RESUMO

OBJECTIVES: There is still some dispute regarding the performance of limited mediastinal lymphadenectomy (LML) even for lung adenocarcinoma ≤ 2 cm. We aimed to recognize the potential candidates who can benefit from LML based on the percentage of histological components (PHC). METHODS: We analyzed 1160 surgical patients with invasive lung adenocarcinoma ≤ 2 cm from seven institutions between January 2012 and December 2015. All histological subtypes were listed in 5% increments by pathological slices. To test the accuracy of frozen section in judging PHC, frozen section slides from 140 cases were reviewed by three pathologists. RESULTS: There were 882 patients with systematic mediastinal lymphadenectomy (SML) and 278 with LML. Multivariable analysis indicated that, the total percentage of micropapillary and solid components (PHCMIP+S) > 5 % was the independent predictor of N2 metastasis (P < 0.001). Overall, recurrence-free survival (RFS) and overall survival (OS) favored SML compared with LML, but the subgroup analysis revealed LML and SML had similar prognosis in the group of PHCMIP+S ≤ 5 %. Moreover, multivariable Cox analysis showed LML (vs. SML) was independently associated with worse prognosis for patients with PHCMIP+S > 5 % (RFS, HR = 2.143, P < 0.001; OS, HR=1.963, P < 0.001), but not for those with PHCMIP+S ≤ 5 % (RFS, P = 0.398; OS, P = 0.298). The sensitivity and specificity of frozen section to intraoperatively identify PHCMIP+S ≤ 5 % were 97.6 % and 84.2 %, respectively. CONCLUSIONS: PHCMIP+S showed the predictive value for N2 metastasis and procedure-specific outcome (LML vs. SML). It may serve as a feasible indicator for identifying proper candidates of LML by using intraoperative frozen section.

2.
Commun Biol ; 3(1): 514, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948821

RESUMO

We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

3.
Endocr Relat Cancer ; 27(10): 583-589, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32856615

RESUMO

Studies have shown that pheochromocytoma (PHEO) is associated with glucose intolerance and decreased insulin sensitivity. In adipocytes, pyruvate dehydrogenase kinase 4 (PDK4) is involved in glucose uptake. However, very little is known about the role of PDK4 in the insulin signaling pathway in the adipose tissue of PHEO patients. We analyzed the expression of adipokines, oxidative stress-related genes, PDK4, phosphorylated AMPK (pAMPK) and phosphorylated IRS1 (pIRS1) in the periadrenal adipose tissue (peri-A) of patients with PHEO and non-functioning adrenal adenoma (NFA). We also investigated the effects of epinephrine on PDK4, pAMPK and pIRS1 in human stromal vascular fraction (SVF) cells, mouse 3T3-L1 preadipocytes and brown preadipocytes. PHEO patients had higher mRNA levels of PGC1α, C/EBPα, C/EBPß, COXII and AP2 and lower mRNA levels of PPARγ in their peri-A than NFA patients. Decreased pAMPK and increased PDK4 and pIRS1 were observed in the peri-A of PHEO patients. PHEO patients also had significantly higher NOX4 protein expression and lower Nrf2 and HO-1 protein expression in their peri-A than NFA patients. In vitro, epinephrine treatment upregulated PDK4 expression, inhibited AMPK phosphorylation and enhanced IRS1 phosphorylation. The knockdown of PDK4 by siRNA upregulated pAMPK and downregulated pIRS1. In conclusion, PDK4 may play an essential role in hypercatecholamine-induced insulin resistance in the periadrenal adipose tissues of PHEO patients.

4.
J Virol ; 94(21)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796065

RESUMO

The humoral immune response against porcine reproductive and respiratory syndrome virus (PRRSV) infection is characterized by a rapid induction of nonneutralizing antibodies (non-NAbs) against nonstructural proteins (NSPs). Here, we systematically investigated the potential mechanism for the induction of PRRSV NSP-specific non-NAbs. Our data suggested that PRRSV NSP-specific antibodies appeared within 10 days after PRRSV infection in vivo In the in vitro model, functional upregulation of swine leukocyte antigen (SLA)-DR was observed in bone marrow-derived dendritic cells (BMDCs) and porcine alveolar macrophages (PAMs), whereas remarkable inhibition at the mRNA level was observed after infection by both PRRSV-1 and PRRSV-2 isolates. Notably, the inconsistency in SLA-DR expression between the mRNA and protein levels resulted from deubiquitination of SLA-DR via the ovarian tumor (OTU) domain of PRRSV NSP2, which inhibited ubiquitin-mediated degradation. Moreover, mass spectrometry-based immunopeptidome analysis identified immunopeptides originating from multiple PRRSV NSPs within SLA-DR of PRRSV-infected BMDCs. Meanwhile, these PRRSV NSP-derived immunopeptides could be specifically recognized by serum from PRRSV-infected piglets. Notably, certain NSP-derived immunopeptides characterized in vitro could be identified from PAMs or hilar lymph nodes from PRRSV-infected piglets. More importantly, an in vitro neutralizing assay indicated that serum antibodies against NSP immunopeptides were unable to neutralize PRRSV in vitro Conversely, certain structural protein (SP)-derived immunopeptides were identified and could be recognize by pig hyperimmune serum against PRRSV, which further indicates that the NSP-derived antibody response is nonprotective in vivo In conclusion, our data suggested that PRRSV infection interferes with major histocompatibility complex class II (MHC-II) molecule-mediated antigen presentation in antigen-presenting cells (APCs) via promoting SLA-DR expression to present immunopeptides from PRRSV NSPs, which contributes to the induction of non-NAbs in vivo IMPORTANCE PRRSV has haunted the swine industry for over 30 years since its emergence. Besides the limited efficacy of PRRSV modified live vaccines (MLVs) against heterogeneous PRRSV isolates, rapid induction of nonneutralizing antibodies (non-NAbs) against PRRSV NSPs after MLV immunization or wild-strain infection is one of the reasons why development of an effective vaccine has been hampered. By using in vitro-generated BMDCs as models to understand the antigen presentation process of PRRSV, we obtained data indicating that PRRSV infection of BMDCs promotes functional SLA-DR upregulation to present PRRSV NSP-derived immunopeptides for evoking a non-NAb response in vivo Our work not only uncovered a novel mechanism for interference in host antigen presentation by PRRSV but also revealed a novel insight for understanding the rapid production of nonneutralizing antibodies against PRRSV NSPs, which may have benefit for developing an effective vaccine against PRRSV in the future.

5.
Int J Infect Dis ; 99: 77-83, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32738487

RESUMO

BACKGROUND: Droplet digital PCR (ddPCR) is a technology that has higher sensitivity than real-time PCR for the identification of trace DNA. However, the use of ddPCR for the detection of Mycobacterium tuberculosis DNA in pathological samples has not been fully studied. METHODS: A total of 65 formalin-fixed and paraffin-embedded (FFPE) specimens were included in this study. Twenty samples with definite results for tuberculosis (TB) were used to establish the ddPCR system for TB detection. ddPCR was then conducted to detect TB DNA in the 45 patients who were classified as 'possible TB' (real-time PCR results in the gray area, Ziehl-Neelsen staining-negative, and hematoxylin and eosin staining showing morphology suspicious for TB). The clinical treatment and disease outcomes were followed to assess the accuracy of ddPCR in the detection of TB DNA. RESULTS: Among the 45 possible TB samples, 26 were ddPCR-positive, 12 were ddPCR-negative, and seven were in the gray area. ddPCR improved the positive rate of 57.8% (26/45) for the samples that were in the gray area by real-time PCR. Moreover, several patients received anti-TB therapy, and the effective ratio of therapy for the ddPCR-positive, ddPCR-negative, and ddPCR-gray area cases was 61.9% (13/21), 50.0% (2/4), and 33.3% (1/3), respectively. CONCLUSIONS: ddPCR is more sensitive for detecting mild TB via FFPE samples than real-time PCR. The ddPCR method is of additional value in the diagnosis of TB from pathological samples.

6.
Small ; : e2000845, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32686359

RESUMO

Fine particulate matter (PM2.5) pollution arouses public health concerns over the world. Increasing epidemiologic evidence suggests that exposure to ambient airborne PM2.5 increases the risk of female infertility. However, relatively few studies have systematically explored the harmful effect of chronic PM2.5 exposure on ovarian function and the underlying mechanisms. In this study, female C57BL/6J mice are exposed to filtered air or urban airborne PM2.5 for 4 months through a whole-body exposure system. It is found that PM2.5 exposure significantly caused the alteration of estrus cycles, reproductivity, hormone levels, and ovarian reserve. The granulosa cell apoptosis via the mitochondria dependent pathway contributes to the follicle atresia. With RNA-sequencing technique, the differentially expressed genes induced by PM2.5 exposure are mainly enriched in ovarian steroidogenesis, reactive oxygen species and oxidative phosphorylation pathways. Furthermore, it is found that increased PM2.5 profoundly exacerbated ovarian oxidative stress and inflammation in mice through the NF-κB/IL-6 signaling pathway. Notably, dietary polydatin (PD) supplement has protective effect in mice against PM2.5-induced ovarian dysfunction.These striking findings demonstrate that PM2.5 and/or air pollution is a critical factor for ovarian dysfunction through mitochondria-dependent and NF-κB/IL-6-mediated pathway, and PD may serve as a pharmaceutic candidate for air pollution-associated ovarian dysfunction.

7.
Sci Adv ; 6(21): eaaz6717, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32671214

RESUMO

The functional relevance and mechanistic basis of the effects of the pyroptosis executioner Gasdermin D (GSDMD) on colitis remain unclear. In this study, we observed that GSDMD protein was activated during intestinal inflammation in a model of chemically induced colitis. GSDMD deficiency exacerbated experimental colitis independent of changes in the microbiota and without affecting the production of antimicrobial peptides. GSDMD deficiency in macrophages, but not epithelial cells, was sufficient to drive this exacerbated experimental colitis. We further demonstrate that GSDMD functions in macrophages as a negative regulator to control cyclic GMP-AMP synthase (cGAS)-dependent inflammation, thereby protecting against colitis. Moreover, the administration of cGAS inhibitor can rescue the colitogenic phenotype in GSDMD-deficient mice. Collectively, these findings provide the first demonstration of GSDMD's role in controlling colitis and a detailed delineation of the underlying mechanism.

8.
Biochim Biophys Acta Mol Cell Res ; 1867(10): 118795, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32668274

RESUMO

Stress granules (SGs) are membraneless organelles formed in the cytoplasm by liquid-liquid phase separation (LLPS) of translationally-stalled mRNA and RNA-binding proteins during stress response. Understanding the mechanisms governing SG assembly requires imaging SG formation in real time. Although numerous SG proteins have been identified, the kinetics of their recruitment during SG assembly has not been well established. Here we used live cell imaging and super-resolution imaging to visualize SG assembly in human cells. We found that IGF2BP proteins formed microscopically visible clusters in living cells almost instantaneously after osmotic stress, followed by fusion of clusters and the recruitment of G3BP1 and TIA1. Rapid clustering of IGF2BP1 was reduced in cells pretreated with emetine that stabilizes polysomes on mRNA. The KH3/4 di-domain and an intrinsically disordered region (IDR) of IGF2BP1 were found to mediate its clustering. Super-resolution imaging confirmed the formation of IGF2BP clusters associated with mRNA at 40 s after osmotic stress. In mature SGs, multiple clusters of poly(A) mRNA were found to associate with the periphery and the interior of a dense granule formed by IGF2BP1. Taken together, our findings revealed a novel, multi-stage LLPS process during osmotic stress, in which rapid clustering of IGF2BP proteins initiates SG assembly.

9.
Genome Biol ; 21(1): 152, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32580738

RESUMO

BACKGROUND: Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on immunotherapy demonstrate the efficacy in reverting the anti-tumoral function of T cells, highlighting the therapeutic potential in targeting certain cell types in TME. However, the functions of other immune cell types remain largely unexplored. RESULTS: We conduct a single-cell RNA-seq analysis of cells isolated from tumor tissue samples of non-small cell lung cancer (NSCLC) patients, and identify subtypes of tumor-infiltrated B cells and their diverse functions in the progression of NSCLC. Flow cytometry and immunohistochemistry experiments on two independent cohorts confirm the co-existence of the two major subtypes of B cells, namely the naïve-like and plasma-like B cells. The naïve-like B cells are decreased in advanced NSCLC, and their lower level is associated with poor prognosis. Co-culture of isolated naïve-like B cells from NSCLC patients with two lung cancer cell lines demonstrate that the naïve-like B cells suppress the growth of lung cancer cells by secreting four factors negatively regulating the cell growth. We also demonstrate that the plasma-like B cells inhibit cancer cell growth in the early stage of NSCLC, but promote cell growth in the advanced stage of NSCLC. The roles of the plasma-like B cell produced immunoglobulins, and their interacting proteins in the progression of NSCLC are further validated by proteomics data. CONCLUSION: Our analysis reveals versatile functions of tumor-infiltrating B cells and their potential clinical implications in NSCLC.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32319283

RESUMO

Photonic detection with narrow spectrum selectivity is very important to eliminate the signal from obtrusive light, which can improve the anti-interference ability of the infrared imaging system. While the self-driving effect inherent to the p-n junction is very attractive in optic-electronic integration, the application of the p-n junction in narrow-band photodetectors is limited by the usual broad absorption range. In this work, a self-powered filterless narrowband near-infrared photodetector based on CuGaTe2/silicon p-n junction was reported. The as-fabricated photodetector exhibited typical narrow-band response which shall be ascribed to the slightly smaller band gap of Si than CuGaTe2 and the restricted photocurrent generation region in the p-n heterojunction by optimizing CuGaTe2 thickness. It is observed that when the thickness of CuGaTe2 film is 143 nm, the device exhibits a response peak centered around 1050 nm with a full-width at half-maximum of ∼118 nm. Further device analysis reveals a specific detectivity of ∼1012 Jones and a responsivity of 114 mA/W under 1064 nm illumination at zero bias. It was also found that an image system based on the narrowband CuGaTe2/Si photodetector showed high noise immunity for its spectral selective characteristics.

11.
Cancer Cytopathol ; 128(8): 545-552, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32286726

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) is an important marker for targeted therapy in patients with advanced non-small cell lung cancer (NSCLC). The samples obtained with minimally invasive biopsy techniques are usually small, and this limits their application in tissue subtyping or molecular profiling. The supernatants obtained after centrifugation of fine-needle aspiration (FNA) samples are typically discarded. However, these fractions might contain cell-free DNA that could be tested for EGFR mutations by genotyping methods that are normally used for plasma analysis. METHODS: In this study, 214 patients with known or suspected NSCLC who underwent FNA were enrolled. The workflow of the supernatants before molecular detection was as follows. The discarded FNA samples (15 mL) were stored in CytoLyt, a cleaning, fixation solution, and 10 mL of each sample was placed in a preservation solution for separation by low-speed centrifugation. The primary supernatants (8 mL) were then separated by high-speed centrifugation to obtain secondary supernatants. DNA was extracted from the supernatants with QIAamp circulating nucleic acid kits (Qiagen) and circulating DNA kits (AmoyDx), and EGFR mutations were assessed with Super-ARMS EGFR detection kits (AmoyDx). The DNA was then extracted from corresponding cell pellets with tissue DNA kits (AmoyDx), and the EGFR status was analyzed with the amplification refractory mutation system and next-generation sequencing methods. RESULTS: All 214 samples yielded an adequate amount of cell-free DNA for EGFR detection. The use of different DNA commercial extraction kits and the DNA contents of tumor cells did not affect the yield of DNA from the supernatants. The external controlled cycle threshold value of the EGFR test was affected by the concentration of the DNA in the supernatants (P < .05). However, the difference in the concentrations of the DNA in the supernatants did not affect the EGFR mutation status. The EGFR-positive rate was 57.5% (123 of 214) in both the supernatants and the pellets from the 214 FNA samples. The concordance between EGFR variants in the supernatants and the corresponding pellets was 97.2%. EGFR mutations were also detected in 3 pellets but not in their corresponding supernatants and in 3 supernatants but not in their corresponding pellets. The supernatants of FNA biopsy samples might represent a new source for gaining information regarding the molecular characteristics of patients for targeted therapy. CONCLUSIONS: Discarded supernatants provided an adequate amount of cell-free DNA for EGFR detection, and this means that the pellets can be reserved for additional morphological and molecular analyses or to avoid repeat biopsies. Analyzing the EGFR status in cell supernatants and pellets might improve detection sensitivity and confer benefits to patients.

12.
Proc Natl Acad Sci U S A ; 117(17): 9173-9179, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32303653

RESUMO

We present a platform for parallel production of standalone, untethered electronic sensors that are truly microscopic, i.e., smaller than the resolution of the naked eye. This platform heterogeneously integrates silicon electronics and inorganic microlight emitting diodes (LEDs) into a 100-µm-scale package that is powered by and communicates with light. The devices are fabricated, packaged, and released in parallel using photolithographic techniques, resulting in ∼10,000 individual sensors per square inch. To illustrate their use, we show proof-of-concept measurements recording voltage, temperature, pressure, and conductivity in a variety of environments.


Assuntos
Eletrônica/instrumentação , Desenho de Equipamento/métodos , Condutividade Elétrica , Fontes de Energia Elétrica , Dispositivos Ópticos/tendências , Silício/química
13.
Genome Biol ; 21(1): 55, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127018

RESUMO

BACKGROUND: While the physical and chemical properties of airborne particulate matter (PM) have been extensively studied, their associated microbiome remains largely unexplored. Here, we performed a longitudinal metagenomic survey of 106 samples of airborne PM2.5 and PM10 in Beijing over a period of 6 months in 2012 and 2013, including those from several historically severe smog events. RESULTS: We observed that the microbiome composition and functional potential were conserved between PM2.5 and PM10, although considerable temporal variations existed. Among the airborne microorganisms, Propionibacterium acnes, Escherichia coli, Acinetobacter lwoffii, Lactobacillus amylovorus, and Lactobacillus reuteri dominated, along with several viral species. We further identified an extensive repertoire of genes involved in antibiotic resistance and detoxification, including transporters, transpeptidases, and thioredoxins. Sample stratification based on Air Quality Index (AQI) demonstrated that many microbial species, including those associated with human, dog, and mouse feces, exhibit AQI-dependent incidence dynamics. The phylogenetic and functional diversity of air microbiome is comparable to those of soil and water environments, as its composition likely derives from a wide variety of sources. CONCLUSIONS: Airborne particulate matter accommodates rich and dynamic microbial communities, including a range of microbial elements that are associated with potential health consequences.

14.
Genomics Proteomics Bioinformatics ; 18(1): 41-51, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32135311

RESUMO

Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

15.
J Clin Monit Comput ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189165

RESUMO

We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.

16.
J Diabetes Res ; 2020: 9084567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090125

RESUMO

Background: The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). Methods: In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate. Results: The expressions of UCP-1, PGC-1α, ATGL, and CD36 in BAT of DM mice were all downregulated, which could be upregulated by exendin-4 treatment with significant effects on ATGL and CD36. BAT-excision exacerbated high blood glucose (BG) with no significant effect on the serum lipid level. Exendin-4 significantly lowered the level of serum triglycerides (TG) and low-density lipoprotein- (LDL-) c, 24 h urine albumin, and 8-OH-dG; improved renal fibrosis and lipid accumulation; and activated renal AMP-activated protein kinase (AMPK) in diabetic mice regardless of BAT excision. In vitro, there was no significant effect of exendin-4 on brown or white adipogenesis. However, exendin-4 could improve lipid accumulation and myofibroblast-like phenotype transition of mesangial cells induced by oleate via activating the AMPK pathway. Conclusions: Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation.

17.
Diagn Pathol ; 15(1): 9, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005253

RESUMO

BACKGROUND: Non-surgical cytological specimens are adequate not only for accurate histological subtyping but also for molecular profiling. A modified amplification refractory mutation system polymerase chain reaction (ARMS PCR), known as SuperARMS PCR, was improved by optimizing the primers designation, which provides a higher sensitivity and specificity approach for free plasma DNA detection. It is unclear whether SuperARMS PCR detects epidermal growth factor receptor (EGFR) mutations in cytology samples. The aim of this study was to compare the EGFR mutations detected by ARMS PCR and SuperARMS PCR in cytology samples derived from advanced non-small cell lung cancer (NSCLC) patients. METHODS: From March 2016 to March 2018, a total of 234 cytological samples were obtained from primary or metastatic lesions of NSCLC, including 144 fine-needle aspirations (FNAs), 36 endobroncheal ultrasonography (EBUS) FNAs, 36 transbronchial needle aspirations (TBNAs) and 18 pleural effusion (PLEs). EGFR mutations were simultaneously detected using an ADx-ARMS EGFR kit (Amoy Diagnostics CO., ltd., Xiamen, China) and an ADx-SuperARMS EGFR kit (Amoy Diagnostics CO., ltd., Xiamen, China). Digital droplet PCR (ddPCR) and next-generation sequencing (NGS) were further used to verify the EGFR mutant inconsistent samples. RESULTS: All of the 234 patients with advanced or recurrent NSCLC were diagnosed and assessed by two cytopathologists, and their EGFR mutation statuses were successfully detected by ARMS and SuperARMS. Importantly, the SuperARMS and ARMS methods showed a highly concordant result of 94.0% (220/234) (95%CI: 85.0, 95.0%). The positive rate of the SuperARMS was higher than the ARMS in the cytology samples for EGFR detection (46.2% vs. 40.2%). The specific EGFR mutation sites in 16 samples (6.8%) were not completely consistent between the SuperARMS and ARMS. A total of 14 patients showed EGFR mutations when detected by SuperARMS, but by ARMS there were EGFR wild-type. Two patients were detected as having one more EGFR mutation site by SuperARMS than by ARMS. ddPCR and NGS were used to further confirm the EGFR mutations in these inconsistent samples. Eight samples had the same mutation results as the SuperARMS, and 6 samples were not verified because the remaining DNA was insufficient. A total of 78 EGFR mutation patients received Tyrosine Kinase Inhibitor (TKI) treatment. The overall objective response rate (ORR) was 88.5% (69/78) for EGFR TKI treatment. CONCLUSION: SuperARMS showed a high sensitivity and specificity for EGFR detection and thus, is expected to become a routine test in the clinic to be used as a widely available, easy-to-operate and sensitive method for EGFR mutation detection in liquid-based cytology samples.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Citodiagnóstico , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
BMC Cardiovasc Disord ; 20(1): 53, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013892

RESUMO

BACKGROUND: The optimal duration of oral anticoagulant therapy for patients with venous thromboembolism (VTE) remains highly uncertain in clinical practice. It is essential to accurately assess the effect of anticoagulant therapy in reducing recurrent VTE against the risk of inducing major bleeding. METHODS: Randomized controlled trials were identified by searching PubMed, Web of Science, Embase, and the Cochrane library, reporting rates of recurrent VTE and major bleeding in patients taking Vitamin K Antagonists (VKA) with VTE and comparing different durations. RESULTS: Eleven RCTs with 3109 participants utilizing varied durations were included in the meta-analysis. Longer VKA therapy was associated with significantly lower rates of VTE recurrence compared with shorter duration of VKA therapy (OR 0.75, 95%CI 0.57-0.99), with significant difference noted in major bleeding risk (OR 2.31, 95%CI 1.17-4.56). During anticoagulation duration, patients treated by 6-month VKA had higher risk of major bleeding compared with 3-month VKA regimen (OR 33.45, 95%CI 2.00-559.67). CONCLUSIONS: Regimen longer than 6 months did not show statistical elevation of major bleeding risk. VKA treatment strongly reduces the risk of recurrent VTE during anticoagulation therapy. The absolute risk of recurrent VTE declines over time while the risk for major bleeding after 6 months' treatment did not demonstrate a continuous significant increase with extended duration of VKA therapy.


Assuntos
Anticoagulantes/administração & dosagem , Tromboembolia Venosa/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Esquema de Medicação , Hemorragia/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Adulto Jovem
19.
Elife ; 92020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999253

RESUMO

1300 nm three-photon calcium imaging has emerged as a useful technique to allow calcium imaging in deep brain regions. Application to large-scale neural activity imaging entails a careful balance between recording fidelity and perturbation to the sample. We calculated and experimentally verified the excitation pulse energy to achieve the minimum photon count required for the detection of calcium transients in GCaMP6s-expressing neurons for 920 nm two-photon and 1320 nm three-photon excitation. By considering the combined effects of in-focus signal attenuation and out-of-focus background generation, we quantified the cross-over depth beyond which three-photon microscopy outpeforms two-photon microscopy in recording fidelity. Brain tissue heating by continuous three-photon imaging was simulated with Monte Carlo method and experimentally validated with immunohistochemistry. Increased immunoreactivity was observed with 150 mW excitation power at 1 and 1.2 mm imaging depths. Our analysis presents a translatable model for the optimization of three-photon calcium imaging based on experimentally tractable parameters.

20.
Antiviral Res ; 175: 104716, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31981575

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is the most economically important infectious disease affecting the global swine industry, especially since vaccination has had limited impact on PRRSV prevention and control. In this study, the monoclonal antibody PR5nf1 (Mab-PR5nf1, IgM isotype) was shown to react with heterogeneous PRRSV isolates belonging to both PRRSV-1 and PRRSV-2 species. Pepsin digestion of Mab-PR5nf1 did not affect Mab binding to virions, as F(ab)2 fragments demonstrated the same reactivity as undigested Mab. Upon further investigation, Mab-PR5nf1 could neutralize all tested PRRSV isolates of both PRRSV-1 and PRRSV-2, suggesting it was a broadly neutralizing Mab against PRRSV. Interestingly, Mab-PR5nf1 appeared to recognize a specific virus epitope that required post-translational modification within the host cellular Golgi apparatus. Deglycosylation of PRRSV virions with PNGase F abolished Mab binding, suggesting that a novel Mab-binding epitope may exist that confers cross-protection against isolates of both PRRSV species. Additionally, immunization of mice with a cocktail of inactivated PRRSV virus and Mab-PR5nf1 enhanced cell-mediated immunity, as determined by IFN-γ ELIspot. In conclusion, this is the first report describing a novel Mab that recognizes a conserved epitope common to both PRRSV-1 and PRRSV-2 and provides valuable insights to guide future PRRSV vaccine development.

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