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1.
Am J Hypertens ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618887

RESUMO

BACKGROUND: Previous studies have shown that hydrogen (H2) can antagonize the fibrosis of various organs. We investigated whether hydrogen-rich saline (HRS) can attenuate myocardial fibrosis in spontaneously hypertensive rats (SHR) and clarified the mechanisms involved. METHODS: We examined the effect of HRS and pirfenidone (PFD) on myocardial fibrosis in SHR. Systolic blood pressure, left ventricular mass index (LVMI) and heart weight index (HWI) were measured, Masson trichrome staining was performed. We assessed the role of superoxide dismutase (SOD), malondialdehyde (MDA), Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, and tissue inhibitors of metalloproteinases (TIMPs) in myocardium. We detected the concentrations of procollagen type-I C-terminal propeptide (PICP), procollagen type-III N-terminal propeptide (PIIINP), and angiotensin II (AngII) in rat serum. Furthermore, the relative protein levels of the TGFß/Smad pathway were tested. RESULTS: We discovered that HRS decreases LVMI (P<0.05) and HWI(P<0.05) in vivo. Compared to model group, HRS decreases the level of collagen volume fraction(P<0.0001), collagen I(P<0.001), and collagen III(P<0.001) in myocardium, and Ang II(P<0.05), PICP(P<0.001), and PIIINP(P<0.05) in serum. In addition, HRS down-regulates the expression of MDA(P<0.01), α-SMA(P<0.05), and TIMPs(P<0.05), and increased SOD(P<0.05). Furthermore, HRS down-regulated the expression levels of TGF-ß1(P<0.0001), Smad3(P<0.0001), and Smad2/3(P<0.001), but had no effect on Smad7 expression(P>0.05). PFD had similar effect compared with HRS and control group. CONCLUSIONS: HRS reduced oxidative stress and improved myocardial collagen content, which may be related to inhibition of the TGF-ß signaling pathway.This suggests that HRS is an effective therapeutic strategy for myocardial fibrosis.

2.
Blood ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34614146

RESUMO

Observational studies and standalone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of FL patients in the pre- and post-rituximab era to identify clinical factors predicting POD24. Logistic regression models evaluated the association between clinical factors and POD24. Cox regression evaluated the association between POD24 as a time-dependent factor and subsequent overall survival (OS). A landmark analysis evaluated the association of POD24 on OS for the subset of patients who were alive at 24 months post trial registration. Patients without progression at 24 months at baseline had favorable performance status (PS), limited stage (I/II) disease, low FLIPI risk score, normal baseline hemoglobin, and normal baseline beta 2 microglobulin (B2M). In a multivariable logistic regression model, male gender (odds ratio (OR) = 1.30), PS >= 2 (OR = 1.63), B2M (>= 3mg/L) (OR = 1.43), and high FLIPI risk score (3 - 5) (OR = 3.14) were associated with increased risk of progression before 24 months. In the time-dependent Cox model and the 24 month landmark analysis, POD24 was associated with poor subsequent OS (hazard ratio (HR) = 4.85 and HR = 3.06, respectively). This is the largest pooled analysis using clinical trials data validating POD24 as a robust indicator of poor FL survival and identified clinical predictors of early death and progression that can aid in building comprehensive prognostic models incorporating clinical and molecular predictors of POD24.

3.
Mol Biotechnol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554391

RESUMO

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. The purpose of this study was to investigate the potential functional role of long non-coding RNA TUG1 in high glucose (HG)-stimulated human retinal microvascular endothelial cells (hRMECs). The results demonstrated that following 72 h of HG stimulation, enhanced proliferation, migration, and tube formation process were observed in hRMECs. Moreover, HG treatment markedly increased TUG1 expression in hRMECs, and knockdown of TUG1 notably restrained the aberrant phenotypes of hRMECs induced by HG. Mechanistically, TUG1 may serve as a competing endogenous RNA (ceRNA) for miR-145, thereby blocking the repression on VEGF-A in hRMECs. Rescue experiments further indicated that inhibition of miR-145 abolished the beneficial role of TUG1 knockdown in HG-treated hRMECs. Our data suggested that knockdown of TUG1 protects hRMECs against HG stimulation partly by regulating miR-145/VEGF-A axis.

4.
Biochem J ; 478(19): 3539-3553, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524407

RESUMO

Calpain proteolysis contributes to the pathogenesis of heart failure but the calpain isoforms responsible and their substrate specificities have not been rigorously defined. One substrate, Junctophilin-2 (JP2), is essential for maintaining junctional cardiac dyads and excitation-contraction coupling. We previously demonstrated that mouse JP2 is cleaved by calpain-1 (CAPN1) between Arginine 565 (R565) and Threonine 566 (T566). Recently, calpain-2 (CAPN2) was reported to cleave JP2 at a novel site between Glycine 482 (G482) and Threonine 483 (T483). We aimed to directly compare the contributions of each calpain isoform, their Ca2+ sensitivity, and their cleavage site selection for JP2. We find CAPN1, CAPN2 and their requisite CAPNS1 regulatory subunit are induced by pressure overload stress that is concurrent with JP2 cleavage. Using in vitro calpain cleavage assays, we demonstrate that CAPN1 and CAPN2 cleave JP2 into similar 75 kD N-terminal (JP2NT) and 25 kD C-terminal fragments (JP2CT) with CAPNS1 co-expression enhancing proteolysis. Deletion mutagenesis shows both CAPN1 and CAPN2 require R565/T566 but not G482/T483. When heterologously expressed, the JP2CT peptide corresponding to R565/T566 cleavage approximates the 25 kD species found during cardiac stress while the C-terminal peptide from potential cleavage at G482/T483 produces a 35 kD product. Similar results were obtained for human JP2. Finally, we show that CAPN1 has higher Ca2+ sensitivity and cleavage efficacy than CAPN2 on JP2 and other cardiac substrates including cTnT, cTnI and ß2-spectrin. We conclude that CAPN2 cleaves JP2 at the same functionally conserved R565/T566 site as CAPN1 but with less efficacy and suggest heart failure may be targeted through specific inhibition of CAPN1.

6.
PLoS Genet ; 17(9): e1009760, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491994

RESUMO

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.

7.
Exp Cell Res ; 407(2): 112826, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34508742

RESUMO

INTS6 (integrator complex subunit 6) has been reported as a tumor suppressor in many cancers. However, the expression and biological function of INTS6 in colorectal cancer (CRC) has not been investigated yet. In this study, we found that INTS6 expression was significantly increased in CRC tissues when compared with normal tissues and was associated with poor prognosis. Downregulation of INTS6 induced G1/S-phase cell cycle arrest, and markedly suppressed the growth of CRC cells and the derived tumors, while overexpression of INTS6 showed opposite effect. Mechanism study revealed that INTS6 increased the levels of phosphorylated AKT (p-AKT) and ERK (p-ERK), and the growth-promoting effect of INTS6 was inhibited by AKT and ERK inhibitors. Besides, INTS6 also affected the expression of two targets of PI3K/AKT and MAPK signaling, c-Myc and CDK2, which contributed to cell cycle alteration. Altogether, the present study has revealed the oncogenic role of INTS6 in CRC, providing a novel therapeutic target for this malignant cancer.

8.
J Cell Mol Med ; 25(19): 9319-9330, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34514705

RESUMO

Long non-coding RNA DLX6 antisense RNA 1 (DLX6-AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6-AS1, microRNA (miR)-193b-3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6-AS1/miR-193b-3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6-AS1, miR-193b-3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6-AS1/miR-193b-3p-related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6-AS1 and HOXA1 were up-regulated, and miR-193b-3p was down-regulated in TC. Depleted DLX6-AS1 or restored miR-193b-3p disturbed cell growth and promoted autophagy. DLX6-AS1 targeted miR-193b-3p and positively regulated HOXA1. miR-193b-3p inhibition mitigated the impaired tumorigenesis induced by down-regulated DLX6-AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6-AS1 depletion hinders TC cell growth and promotes autophagy via up-regulating miR-193b-3p and down-regulating HOXA1.

9.
J Natl Cancer Inst ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505880

RESUMO

BACKGROUND: Disease-free survival with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence, in patients who received adjuvant FOLFOX. Hence, re-evaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. METHODS: Individual patient data from nine randomized studies conducted between 1998 and 2009 were included; three trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (R2WLS) and Copula bivariate (R2Copula) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. RESULTS: Data from a total of 18,396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (pT1-3 & pN1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high/deficient mismatch repair tumors. Trial level correlation between 3-year DFS and 5-year OS remained strong (R2 =0.82, 95% CI = 0.67 to 0.98; R2 =0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. CONCLUSION: Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34465082

RESUMO

Accurate detection, quantitation, and differentiation of polycyclic aromatic hydrocarbons (PAHs) and their isomers in diverse samples is elusive for paper spray ionization mass spectrometry (PSI-MS). To address these issues, herein, for the first time, we propose to fabricate a novel, flexible, and stable paper substrate based on covalent organic frameworks (COFs) via an in situ method under room temperature in air. After embedding gold nanoparticles (AuNPs), this paper substrate (COFs-paper) could further serve as a multifunctional plasmonic matrix (AuNPs-COFs-paper) for dual-wavelength laser-assisted PSI-MS detection of PAHs and feasible paper surface-enhanced Raman scattering (pSERS)-aided isomer discrimination. Taking advantage of the synergistic effect between the AuNPs and COFs present on the novel AuNP-embedded COFs-paper substrate, a satisfied LOD of 0.50 ng/µL for phenanthrene was realized, which improved almost 300 times compared with the naked-paper matrix, and the regression coefficient R2 was up to 0.999. Real sample corn oil-containing PAHs can be efficiently detected and identified using this technique. The established platform has promising potential for on-site chemical analysis with portable PSI-MS and pSERS instruments.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1019-1027, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362477

RESUMO

OBJECTIVE: To detect the expression of different transcripts of lactamase ß(LACTB) gene in leukemic cell lines. METHODS: NCBI website and DNAstar software were used to detect the Bioinformatics analysis of LACTB. The expression of different transcripts of LACTB gene in leukemic cell lines (THP-1, HL60, K562, U937, Jurkat and Raji) was detected by reverse transcription PCR (RT-PCR), DNA and clone sequencing; the expression of different transcripts of LACTB gene in leukemic cell lines was detected by Quantitative Real-time PCR. RESULTS: There were a variety of splicing isomers in LACTB, and it could produce a variety of protein isomers with conserved N-terminal and different C-terminal, moreover, there were many splice isoforms of LACTB in leukemia cell lines, and there were different expression patterns in different cell lines, including XR1, V1, V2 and V3. The expression of total LACTB showed high in HL60 cells, while low in Raji cells, and the difference was statistically significant (P<0.05). The V1 was high expression in U937 cells but low in Raji cells, and the difference was statistically significant (P<0.05). V2 was high expression in HL60 cells but lowly in Raji cells, and the difference was statistically significant (P<0.05). The expression of V3 was low in THP-1 cells, which was significantly different as compared with that in normal bone marrow (P<0.05). CONCLUSION: The reaserch found that there are many splice isomers of LACTB in leukemic cell lines, and there are different expression patterns in different cell lines.


Assuntos
Processamento Alternativo , Leucemia , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , beta-Lactamases/genética , Células HL-60 , Humanos , Leucemia/genética , Splicing de RNA , Células U937
12.
J Natl Cancer Inst ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405233

RESUMO

BACKGROUND: Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing. METHODS: Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided. RESULTS: Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers. CONCLUSION: Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.

13.
Front Immunol ; 12: 674871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290700

RESUMO

Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial-immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial-immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea.

14.
Ann Surg ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34225302

RESUMO

OBJECTIVE: Compare oncological long-term and short-term outcomes between patients with distal cT2N0 rectal cancer treated with chemoradiotherapy and local excision (CRT+LE) and patients treated with total mesorectal excision (TME). SUMMARY BACKGROUND DATA: Previous studies showed that CRT+LE is equivalent to TME in local tumor control and survival for T2N0 rectal cancer. METHODS: Seventy-nine patients with cT2N0 rectal adenocarcinoma treated with CRT+LE in the ACOSOG Z6041 trial were compared to cohort of 79 patients with pT2N0 tumors treated with upfront TME in the Dutch TME trial. Survival, short-term outcomes, and health-related quality of life (HRQOL) were compared between groups. RESULTS: Three patients (4%) in the CRT+LE group required abdominoperineal resection, compared with 31 (40%) in the TME group. Forty TME patients (51%) required a permanent stoma. CRT-related toxicity occurred in 43% of the CRT+LE patients; however, TME patients had a higher rate of complications requiring reoperation (1 vs. 9%; p = 0.03). Five-year disease-free survival (88.2% [CI, 77.7-93.9%] vs. 88.3% [CI, 78.7-93.7%]; p = 0.88) and overall survival (90.3% [CI, 80.8-95.3%] vs. 88.4% [CI, 78.9-93.8%]; p = 0.82) were similar in the two groups. Compared to baseline, overall HRQOL decreased in the CRT+LE group and improved in the TME group. In both groups, patients with sphincter preservation had worse HRQOL scores 1 year after surgery. CONCLUSIONS: In patients who underwent CRT+LE, oncological outcomes were similar to those of patients who underwent TME, with fewer complications requiring reoperation but significant CRT toxicity. Although overall HRQOL decreased in the CRT+LE group and improved in TME patients, when considering anorectal function, results were worse in both groups.

15.
Sci Rep ; 11(1): 11960, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099822

RESUMO

Superhydrophobic sponges have considerable potential for oil/water separation. Most of the methods used for superhydrophobic modification of sponges require toxic or harmful solvents, which have the drawbacks of hazardous to environment, expensive, and complex to utilize. Moreover, the hydrophobic layer on the surface of sponge is often easily destroyed. In this paper, a highly efficient superhydrophobic sponge with excellent reusability was developed by using a facile, simple and environmentally friendly dopamine biomimetic bonding method. Different types of sponges, such as melamine, polyethylene or polyurethane sponge wastes, were used as raw materials to prepare superhydrophobic sponges, which possess the advantages of inexpensive and abundant. The effects of different dopamine polymerization time and different hydrophobic agent dosage on the hydrophobicity and oil absorption capacity of melamine sponges were optimized. The study results showed that the water contact angle of the superhydrophobic sponge could reach 153° with excellent organic solvent absorption capacity of 165.9 g/g. Furthermore, the superhydrophobic sponge retained approximately 92.1% of its initial absorption capacity after 35 reutilization cycles. More importantly, the dopamine biomimetic bonding superhydrophobic modification method can be used for different types of sponges. Therefore, a universally applicable, facile, simple and environmentally friendly superhydrophobic modification method for sponges was developed.

16.
J Natl Cancer Inst ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061178

RESUMO

BACKGROUND: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. METHODS: PTS data of 9,277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemo, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs. chemotherapy alone). All statistical tests were 2-sided. RESULTS: Compared to right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 v 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67-0.76, P<.001) and PFS (median = 8.6 v 7.5 months; HRadj = 0.80, 95% CI = 0.75-0.84, P<.001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction<.001): left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53-0.66; PFS HRadj =0.68, 95% CI = 0.61-0.75), but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75-0.97, P = .01; PFS HRadj = 0.77, 95% CI = 0.67-0.88, P<.001), but not for right-sidedness. CONCLUSIONS: The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.

17.
Curr Med Sci ; 41(3): 597-609, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34169426

RESUMO

We performed a bioinformatics analysis with validation by multiple databases, aiming to evaluate the diagnostic and prognostic value of Kelch-like ECH-associated protein 1 (Keap1) mRNA for lung cancer, and to explore possible mechanisms. Diagnostic performance of Keap1 mRNA was determined by receiver operating characteristic (ROC) curve analysis. Prognostic implication of Keap1 mRNA was estimated by Kaplan-Meier survival analysis. Co-expressed genes with both Keap1 and Nfe2L2 were identified by LinkedOmics. Mechanisms of Keap1-Nfe2L2-co-expressed genes underlying the pathogenesis of lung cancer were explored by function enrichment and pathway analysis. The ROC curve analysis determined a good diagnostic performance of Keap1 mRNA for lung squamous cell carcinoma (LUSC), with an area under the ROC curve (AUC) of 0.833, sensitivity of 72.7%, and specificity of 90.6% (P<0.001). Multivariate Cox regression recognized high Keap1 mRNA to be an independent risk factor of mortality for overall lung cancer [hazard ratio (HR): 11.034, P=0.044], but an independent antagonistic factor for lung adenocarcinoma (LUAD) (HR: 0.404, P<0.001). Validation by UALCAN and GEPIA supported Oncomine findings regarding the diagnostic value of Keap1 mRNA for LUSC, but denied its prognostic value. After screening, we identified 17 co-expressed genes with both Keap1 and Nfe2L2 for LUAD, and 22 for LUSC, mainly enriched in signaling pathway of oxidative stress-induced gene expression via Nrf2. In conclusion, Keap1 mRNA has a good diagnostic performance, but controversial prognostic efficacy for LUSC. The pathogenesis of lung cancer is associated with Keap1-Nfe2L2-co-expressed genes by signaling pathway of oxidative stress-induced gene expression via Nrf2.

18.
Chem Commun (Camb) ; 57(58): 7152-7155, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34184013

RESUMO

Glass micropipettes are easy to fabricate, have excellent flexibility and stable properties. HKUST-1 and MIL-68(In) are in situ grown in the tip of a micropipette to construct porous nanochannels. After absorbing H2S, the MIL-68(In)-based nanochannel shows effective metal ion responsiveness for Hg2+-detection.


Assuntos
Sulfeto de Hidrogênio/análise , Estruturas Metalorgânicas/química , Adsorção , Vidro/química , Sulfeto de Hidrogênio/isolamento & purificação , Nanoestruturas/química , Porosidade
19.
PLoS Comput Biol ; 17(5): e1008962, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33956788

RESUMO

In the past few years, a wealth of sample-specific network construction methods and structural network control methods has been proposed to identify sample-specific driver nodes for supporting the Sample-Specific network Control (SSC) analysis of biological networked systems. However, there is no comprehensive evaluation for these state-of-the-art methods. Here, we conducted a performance assessment for 16 SSC analysis workflows by using the combination of 4 sample-specific network reconstruction methods and 4 representative structural control methods. This study includes simulation evaluation of representative biological networks, personalized driver genes prioritization on multiple cancer bulk expression datasets with matched patient samples from TCGA, and cell marker genes and key time point identification related to cell differentiation on single-cell RNA-seq datasets. By widely comparing analysis of existing SSC analysis workflows, we provided the following recommendations and banchmarking workflows. (i) The performance of a network control method is strongly dependent on the up-stream sample-specific network method, and Cell-Specific Network construction (CSN) method and Single-Sample Network (SSN) method are the preferred sample-specific network construction methods. (ii) After constructing the sample-specific networks, the undirected network-based control methods are more effective than the directed network-based control methods. In addition, these data and evaluation pipeline are freely available on https://github.com/WilfongGuo/Benchmark_control.


Assuntos
Análise de Célula Única/métodos , Algoritmos , Biologia Computacional/métodos , Redes Reguladoras de Genes , Humanos , RNA-Seq/métodos
20.
Eur J Cancer ; 150: 214-223, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33934058

RESUMO

AIM: report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. METHODS: In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). RESULTS: Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). CONCLUSIONS: Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

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