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Cisplatin (DDP) remains the backbone of chemotherapy for non-small cell lung cancer (NSCLC), yet its clinical efficacy is limited by DDP resistance. learn more We aim to investigate the role of the SET and MYND domain-containing protein 3 (SMYD3) in DDP resistance of NSCLC.

Expression pattern of SMYD3 was determined in NSCLC tissues using qRT-PCR, which also validated its correlation with NSCLC clinicopathological stages. Impacts of SMYD3 on DDP resistance were evaluated by knocking down SMYD3 in DDP-resistant cells and overexpressing it in DDP-sensitive cells, and assessed for several phenotypes IC

by MTT, long-term proliferation by colony formation, apoptosis and cell-cycle distribution by flow cytometry. The interaction between Ankyrin Repeat and KH Domain Containing 1 (ANKHD1) and SMYD3 was examined by co-immunoprecipitation and immunofluorescence. The transcriptional regulation of SMYD3 on cyclin-dependent kinase 2 (CDK2) promoter regions was confirmed using chromatin-immunoprecipitation. The in vivo experiments using DDP-resistant cells with altered SMYD3 and ANKHD1 expression were further performed to verify the SMYD3/ANKHD1 axis.

Highly expressed SMYD3 was observed in NSCLC tissues or cells, acted as a sensitive indicator for NSCLC, correlated with higher TNM stages or resistant to DDP treatment, and shorter overall survival. The promotion of SMYD3 on DDP resistance requires co-regulator, ANKHD1. CDK2 was identified as a downstream effector. In vivo, SMYD3 knockdown inhibited the growth of DDP-resistant NSCLC cells, which was abolished by ANKHD1 overexpression.

SMYD3 confers NSCLC cells chemoresistance to DDP in an ANKHD1-dependent manner, providing novel therapeutic targets to overcome DDP resistance in NSCLC .

SMYD3 confers NSCLC cells chemoresistance to DDP in an ANKHD1-dependent manner, providing novel therapeutic targets to overcome DDP resistance in NSCLC .The biomarker significance of IL-35, chemokines (CXCL9 and CXCL10) and human beta-defensins (hBD2 and hBD3) was determined in pulmonary tuberculosis (TB) of 105 Iraqi patients; 37 had active disease, 41 had multi-drug resistant (MDR) PTB and 27 had a relapse of TB. A control sample of 79 healthy persons was also included. Serum levels of markers were assessed using enzyme-linked immunosorbent assay kits. Kruskal-Wallis test together with Dunn-Bonferroni post hoc test revealed significance differences between patients and controls in levels of IL-35, CXCL9, CXCL10 and hBD3, while hBD2 showed no significant difference. Receiver operating characteristic analysis demonstrated that CXCL10 and hBD3 were the most significant markers in predicting TB, particularly active disease. Logistic regression analysis proposed the susceptibility role of CXCL10 in TB. Gender- and age-dependent variations were also observed. Spearman's rank correlation analysis showed different correlations between markers in each group of patients and controls. In conclusion, CXCL10 was up-regulated in serum of TB patients, while hBD3 showed down-regulated level. Both serum proteins are possible candidate biomarkers for evaluation of TB progression, particularly in active disease.

With the help of quantitative computed tomography (QCT), it is possible to identify smoking-associated airway remodeling. However, there is currently little information on whether QCT-based airway metrics are sensitive to early airway wall remodeling in subclinical phases of smoking-associated airway disease. This study aimed to evaluate a predictive model that normalized airway parameters and investigate structural airway alterations in smokers with normal-looking CT using the normalization scheme.

In this retrospective analysis, 222 non-smokers (male 97, female 125) and 69 smokers (male 66, female 3) from January 2014 to December 2016 were included, and airway parameters were quantitatively analyzed. To control inter-subject variability, multiple linear regressions of tracheal wall thickness (WT), diameter (D), and luminal area (LA) were performed, adjusted for age, sex, and height. Using this normalization scheme, airway parameters with matched generation were compared between smokers and non-smokers.

Using the normalization scheme, it was possible to assess generation-based structural alterations of the airways in subclinical smokers. Smokers showed diffuse luminal narrowing of airways for most generations (P < 0.05, except 3rd generation), no change in wall thickness of the proximal bronchi (1st-3rd generation), and a thinning of distal airways (P <0.05, ≥4th generation).

QCT assessment for subclinical smokers can help identify minimal structural changes in airways induced by smoking.

QCT assessment for subclinical smokers can help identify minimal structural changes in airways induced by smoking.

This study aimed to identify preoperative MR imaging features for predicting early recurrence after curative resection of solitary hepatocellular carcinoma (HCC) without microvascular invasion (MVI).

124 patients with MVI-negative HCC who underwent preoperative dynamic contrast-enhanced 1.5-T MR imaging before surgical resection were included. Liver Imaging Reporting and Data System (LI-RADS v2018) imaging features and three non-LI-RADS MR imaging features for predicting early recurrence (intrahepatic recurrence<2 years) were identified by univariable and multivariable analyses. A nomogram was constructed for individualized risk estimation, and its predictive accuracy and discriminative ability were identified by concordance index (C-index) and calibration curve.

In multivariable analysis, tumor size (p = 0.045), nonsmooth tumor margin (p = 0.013), and presence of mosaic architecture (p = 0.035) were independent significant variables associated with early recurrence. These were all incorporated to establish the nomogram. The C-index of the nomogram was 0.743 (95 % CI 0.697-0.788).

At dynamic contrast-enhanced MR imaging, tumor size, nonsmooth tumor margin, and presence of mosaic architecture may be helpful to predict early recurrence of solitary HCC without MVI after curative resection.

At dynamic contrast-enhanced MR imaging, tumor size, nonsmooth tumor margin, and presence of mosaic architecture may be helpful to predict early recurrence of solitary HCC without MVI after curative resection.