Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

Long noncoding RNA LINC00482 silencing sensitizes non-small cell lung cancer cells to cisplatin by downregulating CLASRP via E2F1.

Long noncoding RNA LINC00482 (LINC00482) is dysregulated in non-small cell lung cancer cells (NSCLC). Herein, this research examined the actions and specific mechanisms of LINC00482 in cisplatin (DDP) resistance in NSCLC. LINC00482 expression was assessed using RT-qPCR in clinical NSCLC tissues and cell lines. Knockdown and ectopic expression assays were conducted in A549 and HCC44 cells, followed by determination of cell proliferation with CCK-8 and clone formation assays, apoptosis with flow cytometry, and DDP sensitivity. The association between LINC00482, E2F1, and CLASRP was evaluated with dual-luciferase reporter, ChIP, and RIP assays. The role of LINC00482 in NSCLC was confirmed in nude mice. NSCLC tissues and cells had upregulated LINC00482 expression. LINC00482 was mainly localized in the cell nucleus, and LINC00482 recruited E2F1 to enhance CLASRP expression in NSCLC cells. LINC00482 knockdown enhanced the DDP sensitivity and apoptosis of NSCLC cells while reducing cell proliferation, which was negated by overexpressing CLASRP. LINC00482 knockdown restricted tumor growth and enhanced DDP sensitivity in NSCLC in vivo. LINC00482 silencing downregulated CLASRP through E2F1 to facilitate the sensitivity to DDP in NSCLC.

A systematic review and meta-analysis of risk factors for reoperation after degenerative lumbar spondylolisthesis surgery.

BACKGROUND: Considering the high reoperation rate in degenerative lumbar spondylolisthesis (DLS) patients undergoing lumbar surgeries and controversial results on the risk factors for the reoperation, we performed a systematic review and meta-analysis to explore the reoperation rate and risk factors for the reoperation in DLS patients undergoing lumbar surgeries. METHODS: Literature search was conducted from inception to October 28, 2022 in Pubmed, Embase, Cochrane Library, and Web of Science. Odds ratio (OR) was used as the effect index for the categorical data, and effect size was expressed as 95% confidence interval (CI). Heterogeneity test was performed for each outcome effect size, and subgroup analysis was performed based on study design, patients, surgery types, follow-up time, and quality of studies to explore the source of heterogeneity. Results of all outcomes were examined by sensitivity analysis. Publication bias was assessed using Begg test, and adjusted using trim-and-fill analysis. RESULTS: A total of 39 cohort studies (27 retrospective cohort studies and 12 prospective cohort studies) were finally included in this systematic review and meta-analysis. The overall results showed a 10% (95%CI: 8%-12%) of reoperation rate in DLS patients undergoing lumbar surgeries. In surgery types subgroup, the reoperation rate was 11% (95%CI: 9%-13%) for decompression, 10% (95%CI: 7%-12%) for fusion, and 9% (95%CI: 5%-13%) for decompression and fusion. An increased risk of reoperation was found in patients with obesity (OR = 1.91, 95%CI: 1.04-3.51), diabetes (OR = 2.01, 95%CI: 1.43-2.82), and smoking (OR = 1.51, 95%CI: 1.23-1.84). CONCLUSIONS: We found a 10% of reoperation rate in DLS patients after lumbar surgeries. Obesity, diabetes, and smoking were risk factors for the reoperation.

Combination of the platelet-to-lymphocyte ratio and fibrinogen may predict 5-year overall survival of patient in non-small cell lung cancer treated with surgery.

Background: Non-small cell lung cancer (NSCLC) is a major type of lung cancer with high incidence and mortality. Systemic inflammatory response (SIR) and an imbalance of the coagulation system are both associated with the tumor progression. However, few studies have investigated the prognostic utility of a combination of inflammation and the coagulation system in NSCLC. The combination of platelet-to-lymphocyte ratio (PLR) and fibrinogen (FIB) (PLR-FIB; defined as PLR × FIB) is an indicator reflecting SIR and coagulation concurrently, which have potentiality to predict prognosis of NSCLC. Methods: This retrospective, single-center study included 314 NSCLC patients with surgery. According to a cutoff value for the PLR-FIB, we divided participants into a low-PLR-FIB group and a high-PLR-FIB group. We retrospectively collected the data on 314 patients and used univariate and multivariate analyses to investigate the relationship between the PLR-FIB and survival. Results: Univariate analysis showed that adenosquamous carcinoma (ASC) (P=0.002), high PLR-FIB (P=0.023), and tumor-node-metastasis (TNM) stage III-IV (P<0.001) were associated with a poor outcome. On multivariate analysis, low PLR-FIB [hazard ratio (HR), 0.587; 95% confidence interval (CI): 0.359-0.985; P=0.044], and TNM stage I-II (HR, 0.380; 95% CI: 0.245-0.590; P<0.001) were independent factors of a better prognosis. ASC type was an independent prognostic factor of poor outcome (HR, 5.513; 95% CI: 1.895-16.034; P=0.002). There were no significant differences in patient demographics or clinical characteristics between the two PLR-FIB groups (P>0.05). The 5-year overall survival (OS) rates were 80.8% and 67.9% for the low-PLR-FIB group and high-PLR-FIB group, respectively (P=0.02). Conclusions: Preoperative PLR-FIB was found to be an independent prognostic factor for 5-year overall survival in patients with NSCLC treated with surgery.

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology.

Introduction: Placental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method. Methods: After obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The "ClusterProfiler" R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes. Results: We found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1ß (IL-1ß) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below -5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2. Conclusions: GROA, IL-1ß, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.

Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma.

Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.

Epigallocatechin-3-gallate alleviates galactose-induced aging impairment via gut-brain communication.

The study aimed to determine whether gut-brain communication could be modulated by epigallocatechin-3-gallate (EGCG) in a mouse aging model that was established by daily injection of D-galactose (D-gal) for 10 weeks. Our results showed that EGCG could improve aging-associated changes by increasing the immune organ indexes, brain index, and learning and memory ability in vivo. EGCG-triggered aging prevention was associated with the reduction of lipid peroxidation and elevation of enzymatic and non-enzymatic antioxidant activities in the brain. Concomitantly, treatment of D-gal-induced aging in mice with EGCG significantly reduced corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone, suggesting that EGCG-exerted protection of the aging brain was involved in the inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. Further data concerning intestinal function showed that EGCG could enhance fecal moisture in vitro and reduce the pH value of feces in aging mice when compared to the D-gal group, suggesting that EGCG played beneficial roles in the intestine of aging mice. Moreover, short-chain fatty acids (SCFAs), the mediators of gut-brain communication, were significantly increased in the intestinal contents of aging mice by treatment with EGCG. Therefore, the tea polyphenol EGCG showing anti-aging properties was demonstrated to be implicated in modulating gut-brain communication by attenuating the HPA axis and enhancing the content of SCFAs.

Prediction of Differentially Expressed Genes and a Diagnostic Signature of Preeclampsia via Integrated Bioinformatics Analysis.

Background: Preeclampsia (PE), which has a high incidence rate worldwide, is a potentially dangerous syndrome to pregnant women and newborns. However, the exact mechanism of its pathogenesis is still unclear. In this study, we used bioinformatics analysis to identify hub genes, establish a logistic model, and study immune cell infiltration to clarify the physiopathogenesis of PE. Methods: We downloaded the GSE75010 and GSE10588 datasets from the GEO database and performed weighted gene coexpression network analysis (WGCNA) as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The online search tool for the retrieval of interacting genes and Cytoscape software were used to identify hub genes, which were then used to establish a logistic model. We also analyzed immune cell infiltration. Finally, we verified the expression of the genes included in the predictive model via RT-PCR. Results: A total of 100 and 212 differently expressed genes were identified in the GSE75010 and GSE10588 datasets, respectively, and after overlapping with WGCNA results, 17 genes were identified. KEGG and GO analyses further indicated the involvement of these genes in bioprocesses, such as gonadotropin secretion, immune cell infiltration, and the SMAD and MAPK pathways. Additionally, protein-protein interaction network analysis identified 10 hub genes, six (FLT1, FLNB, FSTL3, INHA, TREM1, and SLCO4A1) of which were used to establish a logistic model for PE. RT-PCR analysis also confirmed that, except FSTL3, these genes were upregulated in PE. Our results also indicated that macrophages played the most important role in immune cell infiltration in PE. Conclusion: This study identified 10 hub genes in PE and used 6 of them to establish a logistic model and also analyzed immune cell infiltration. These findings may enhance the understanding of PE and enable the identification of potential therapeutic targets for PE.

Comparative Transcriptome Analysis of Agrobacterium tumefaciens Reveals the Molecular Basis for the Recalcitrant Genetic Transformation of Camellia sinensis L.

Tea (Camellia sinensis L.), an important economic crop, is recalcitrant to Agrobacterium-mediated transformation (AMT), which has seriously hindered the progress of molecular research on this species. The mechanisms leading to low efficiency of AMT in tea plants, related to the morphology, growth, and gene expression of Agrobacterium tumefaciens during tea-leaf explant infection, were compared to AMT of Nicotiana benthamiana leaves in the present work. Scanning electron microscopy (SEM) images showed that tea leaves induced significant morphological aberrations on bacterial cells and affected pathogen-plant attachment, the initial step of a successful AMT. RNA sequencing and transcriptomic analysis on Agrobacterium at 0, 3 and 4 days after leaf post-inoculation resulted in 762, 1923 and 1656 differentially expressed genes (DEGs) between the tea group and the tobacco group, respectively. The expressions of genes involved in bacterial fundamental metabolic processes, ATP-binding cassette (ABC) transporters, two-component systems (TCSs), secretion systems, and quorum sensing (QS) systems were severely affected in response to the tea-leaf phylloplane. Collectively, these results suggest that compounds in tea leaves, especially gamma-aminobutyrate (GABA) and catechins, interfered with plant-pathogen attachment, essential minerals (iron and potassium) acquisition, and quorum quenching (QQ) induction, which may have been major contributing factors to hinder AMT efficiency of the tea plant.

O-Arm-Navigated, Robot-Assisted Versus Conventional CT Guided Radiofrequency Ablation in Treatment of Osteoid Osteoma: A Retrospective Cohort Study.

Background: Osteoid osteoma is a common benign bone tumor, and clinically there is severe local pain that typically worsens at night. The conventional CT-guided radiofrequency ablation (RFA) was widely used in the treatment of osteoid osteoma (OO), which could result in some radiation-related and imprecise complications due to the overdose of radiation exposure. This study aimed to compare the surgical effect of robot-assisted RFA with O-arm navigation and conventional CT-guided RFA in the treatment of OO. Methods: Sixty-two patients who underwent robot-assisted RFA with O-arm navigation (Robot-RFA, n = 24) or CT-guided RFA (CT-RFA, n = 38) were included in this retrospective cohort study. The mean follow-up time was 23.3 months. The intra-operative data, primary technical success rate, visual analog scale (VAS), and post-operative complications were analyzed. Results: Primary technical success was obtained in 23 patients who had robot-assisted RFA, and 35 patients who had conventional CT-guided RFA. One patient in Robot-RFA group and three patients in CT-RFA group with pain recurrence received repeat-RFA and had a secondary success. Mean operation time and dose of radiation exposure were lower in Robot-RFA group than that in CT-RFA group. The Robot-RFA group took fewer K-wire adjustment times for each patient than the CT-RFA group. There was a statistically significant difference in the mean operation time, dose of radiation exposure, and K-wire adjustment times between the groups (p < 0.05). No complications associated with the procedure were reported in the two groups during the follow-up period. Conclusion: Robot-assisted RFA with O-arm navigation is a safer and more precise strategy in the treatment of osteoid osteoma with less operation time and radiation exposure compared with the conventional CT-guided radiofrequency ablation.

Serum exosomal miR-16-5p functions as a tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in lung adenocarcinoma by regulating PD-L1 expression.

OBJECTIVES: We aimed at investigating whether serum exosomal miR-16-5p could be utilized as an immunotherapy biomarker in lung adenocarcinoma (LUAD) patients administered by programmed cell death ligand-1 (PD-L1) inhibitors, and to evaluate its functions in LUAD progression. METHODS: Sixty LUAD sufferers and 20 healthy controls (HCs) were covered in this work. We applied both IHC and WB to examine PD-L1 level in clinical tissue samples and utilized WB to quantify PD-L1 expression in LUAD cells and LUAD xenograft tissues, respectively. Transmission electron microscopy (TEM), WB, and nanoparticle tracking analysis (NTA) were executed to confirm the exosomes isolated from serum specimens and cell culture media. To quantify of exosomal miR-16-5p level from serum and culture medium of cultured cell, qRT-PCR experiment was utilized. The connection between tissue PD-L1 level and serum exosomal miR-16-5p expression in PD-L1-positive sufferers administered by PD-L1 inhibitors was verified using Spearman correlation coefficient analysis. In addition, the overall survival (OS) and progression-free survival (PFS) rates among PD-L1 inhibitor managed sufferers were acquired through a follow-up visit. Finally, we used a group of assays, including 5-bromo-2'-dexoyuridine (BrdU) and colony formation test, wound healing experiment, flow cytometry, and nude mice xenograft experiment, to explore the functions of circulating exosomal miR-16-5p on LUAD cell proliferation, apoptosis, and migration, as well as tumor development, respectively. RESULTS: PD-L1 expression was positively related to T stage (tumor size stage), and PD-L1 inhibitor treatment reduced the PD-L1 expression and mitigated T stage in PD-L1-positive LUAD sufferers. For PD-L1-positive LUAD sufferers, elevated PD-L1 expression or reduced serum exosomal miR-16-5p level were linked to longer PFS and OS upon PD-L1 inhibitor treatment. The number of exosomes in patient's serum was more than that in the serum of healthy individuals, and PD-L1 inhibitor treatment decreased the number of serum-derived exosomes in PD-L1-positive LUAD sufferers. Exosome-derived miR-16-5p was downregulated in patient's serum and cell culture medium, and this was negatively linked to tumor stage and PD-L1 expression. Meanwhile, PD-L1 inhibitor treatment could increase the serum exosomal miR-16-5p expression, and the expression change of serum exosomal miR-16-5p was diametrically related to PD-L1 after the treatment. Moreover, the overexpression of PD-L1 accelerated tumor growth and decreased the exosomal miR-16-5p content in cell culture media, while exosomal miR-16-5p overexpression in cell culture media inhibited tumor development by decreasing the PD-L1 expression. Exosomal miR-16-5p overexpression in cell culture media also depressed LUAD cell proliferation and migration, and stimulated cell apoptosis, especially in the cells which cultured in the mediums with PD-L1 inhibitor in vitro. CONCLUSIONS: Serum exosomal miR-16-5p may be a latent tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in LUAD by regulating the PD-L1 expression.

Activation of the Hedgehog pathway mediates resistance to epidermal growth factor receptor inhibitors in non-small cell lung cancer.

The current study aimed to investigate the function of the Hedgehog pathway and its association with epithelial-mesenchymal transition (EMT) in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). Lung tumor tissue specimens from EGFR TKI-resistant patients, including those with brain metastases, had hyperactive Hedgehog signaling compared with those from TKI-sensitive patients. SHH stimulation promoted GLI1 activation as well as cell motility in parental PC9 cells while suppressing gefitinib-induced apoptosis in gefitinib-resistant cells. SHH also promoted EMT in parental PC9 cells via E-cadherin suppression and N-cadherin and vimentin upregulation. The knockdown of GLI1 exhibited the opposite effects. Besides, SHH induced, whereas GLI1 knockdown reversed gefitinib resistance in xenograft tumors. The Hedgehog pathway inhibitor GDC-0449 synergized with gefitinib to increase xenograft tumor sensitivity to chemotherapy and extend survival in tumor-bearing animals. These results suggest the Hedgehog pathway mediates EGFR TKI resistance and induces EMT in NSCLC, representing a potential therapeutic target to defeat TKI resistance.

Development and Application of a Fast Gas Chromatographic Method Offer New Insights into l-theanine Production Regulation in Camellia sinensis L.

Tea is the most consumed beverage worldwide, and l-theanine in tea leaves significantly affects their flavor and market quality. We have developed and validated a fast and reliable gas chromatographic method with flame ionization detection (GC-FID) to quantify l-theanine after its extraction from Camellia sinensis (tea plant) and derivatization. The procedure was completed in 40 min, from extraction to chromatographic analysis, with a recovery rate of more than 93% and allowing a high sample throughput. The GC-FID intraday precision was within 0.57-2.28%, while the interday precision ranged from 1.57 to 13.48%. The intraday accuracy ranged from -6.84 to 5.26%, while the interday accuracy ranged from -1.08 to 3.12%. The limit of detection was 2.28 µg/mL, and the limit of quantification was 6.47 µg/mL. The GC-FID method was validated by high-performance liquid chromatography with UV detection (HPLC-UV) and was used to investigate the biosynthesis and regulation of l-theanine in tea plants. We found that plants fed with ethylamine significantly increased l-theanine concentrations in roots, while exogenous supplementation of glutamic acid, carbamide, and glutamine did not significantly affect the l-theanine level in roots. Our results also indicated that roots were not indispensable for the biosynthesis of l-theanine, which was detected in undifferentiated embryonic calluses in concentrations (g/100 g dry weight) as high as in leaves of whole plants (1.67 and 1.57%, respectively) and without any exogenous theanine precursor supplementation.

Concomitant genetic alterations are associated with response to EGFR targeted therapy in patients with lung adenocarcinoma.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered to be more effective than chemotherapy in the treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, in addition to EGFR-sensitive mutations, the genetic factors that affect the prognosis of patients who receive TKI treatment are not yet clear. METHODS: The clinical data of 36 NSCLC patients with EGFR mutation who received TKI treatment were retrospectively analyzed. Liquid re-biopsy with next generation sequencing (NGS) analysis was performed to analyze genetic alterations and potential resistance mechanisms. RESULTS: All of the patients harbored actionable sensitive EGFR mutations by NGS, with the major types being 19del or 21L858R (52.78%, 19/36 and 55.56%, 20/36, respectively). The 3 most frequent accompanying somatic mutations were TP53 (12, 48.4%), KRAS (7, 19.44%) and PIK3CA (3, 8.33%). Concomitant mutations were present in 16 patients (44.44%). The occurrence of co-mutation was found to be significantly related to a history of smoking [87.5% (7 of 8) vs. 32.14% (9 of 28); Pearson chi-square, P=0.005]. Patients who received EGFR-TKIs treatment (P=0.0079) or third-generation EGFR-TKIs only (P=0.0468) had better progression-free survival (PFS). Concomitant mutations were significantly related to lower objective response rates (43.75% vs. 80.0%; P=0.024) and poorer PFS (P<0.001). Patients with concomitant genetic alterations had a worse response after receiving EGFR-TKIs treatment (P=0.0033). CONCLUSIONS: Our research underscores the importance of using multiple molecular profiles. Concomitant genetic alterations were significantly associated with response to EGFR targeted therapy in NSCLC. Therefore, research on multi-drug or sequential therapy to address the covariation that drives drug resistance is urgently needed.

LncRNA ZNF667-AS1 Promotes ABLIM1 Expression by Adsorbing micro RNA-1290 to Suppress Nasopharyngeal Carcinoma Cell Progression.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have been elucidated to play essential roles in cancers, and the recognition of lncRNA expression patterns in nasopharyngeal carcinoma (NPC) may be helpful for indicating novel mechanisms underlying NPC carcinogenesis. Herein, we conducted this study to probe into the function of lncRNA ZNF667-AS1 in NPC progression with the involvement of microRNA-1290 (miR-1290) and actin-binding LIM protein 1 (ABLIM1). MATERIALS AND METHODS: In silico analysis screened differentially expressed genes and miRNAs in NPC and predicted potential mechanisms. ZNF667-AS1 expression was detected in NPC tissues and cells. The gain-and-loss function assays were performed to explore the effects of lncRNA ZNF667-AS1 and miR-1290 in NPC cell biological behaviors. In vivo experiments were further conducted to confirm the in vitro results. RESULTS: In silico analysis predicted that ZNF667-AS1 was diminished in NPC, which may downregulate ABLIM1 through sponging miR-1290. ZNF667-AS1 was poorly expressed in NPC tissues and cells, and overexpression of ZNF667-AS1 inhibited growth of NPC cells. ZNF667-AS1 competitively bound with miR-1290, thereby upregulating ABLIM1. miR-1290 resulted in the promotion of NPC cell progression by suppressing ABLIM1. Overexpression of ZNF667-AS1 or suppression of miR-1290 inhibited tumorigenicity of NPC cells in vivo. CONCLUSION: This study highlights that lncRNA ZNF667-AS1 promotes ABLIM1 expression by sponging miR-1290 to suppress NPC cell progression.

Prospective comparison of indwelling cannulas drain and needle aspiration for symptomatic seroma after mastectomy in breast cancer patients.

AIMS: Postoperative seroma is the most frequent sequelae after mastectomy and axillary surgery with no optimal regimens for seroma resolution recommended in routine clinical. Indwelling cannulas with needle and catheter have been widely used in long-term medication therapies, but evidence of indwelling cannulas in seroma management after mastectomy is lacking. The purpose of this study is to evaluate the feasibility of indwelling cannulas in seroma management after mastectomy. METHODS: Patients who underwent modified radical mastectomy (MRM) and developed symptomatic seroma after removal of the drains between August 2017 and December 2018, were randomized into two groups either indwelling cannulas drain of seroma (Group A) or needle aspiration of seroma (Group B). We prospectively compared the number of visits for seroma, the time from removal of the drain to the final seroma resolution and the cost between the methods. RESULTS: A total of 860 patients underwent MRM between August 2017 and December 2018, among which 86 patients who developed symptomatic seroma after removal of the drains, were randomized into two groups either Group A or Group B. The number of visits for seroma in Group A was 2.35 ± 0.69 times, which was less than those in Group B (4.86 ± 1.06 times). Similarly, the time of drain removal to final seroma resolution in Group A was 4.65 ± 0.78 days, which was shorter than 7.09 ± 1.54 in Group B. In Group A, the total mean cost per patient (25.81 ± 7.71 RMB) was less than the total mean cost per patient (49.30 ± 9.85 RMB) in Group B. Cost savings were noted with using indwelling cannulas in seroma management. CONCLUSION: It is feasible to drain indwelling cannulas drain for postmastectomy seroma, with less visits for patients, rapid seroma resolution and less cost. Indwelling cannulas can be an efficient, cost effective solution to treat symptomatic seroma after breast surgery.

Concurrent versus sequential whole brain radiotherapy and TKI in EGFR-mutated NSCLC patients with brain metastasis: A single institution retrospective analysis.

To examine the outcomes of concurrent versus sequential whole-brain radiotherapy (WBRT) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation.Retrospectively 105 patients with NSCLC, brain metastasis, and EGFR mutation (Affiliated Hospital of Guangdong Medical University, 01/2011 to 12/2014) were grouped as: EGFR-TKIs alone (n = 39, group A), EGFR-TKIs + concurrent radiotherapy (n = 34, group B), and radiotherapy followed by EGFR-TKIs (n = 32, group C).The intracranial objective response rates of groups A, B, and C were 66.7%, 85.3%, and 75%, respectively (P < .05). The median intracranial progression-free survival of groups A, B, and C were 6.8, 12.4, and 9.1 months, respectively (P < .05). The median extracranial progression-free survival of groups A, B, and C were 7.8, 9.4, and 8.3 months, respectively (P > .05).EGFR-TKIs and WBRT by simultaneous application improved the short- and long-term benefits to patients with NSCLC brain metastasis carrying EGFR mutation compared to concurrent application or EGFR-TKIs alone without additional adverse events.

miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1.

BACKGROUND: Non-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance. METHODS: To identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3'-untranslated region (3'-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay. RESULTS: Compared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3'-UTR of FZD1. CONCLUSION: The amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.

LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression.

Large tumor suppressor 2 (LATS2) plays significant roles in tumorigenesis and cancer progression. This study was aimed to analyze the correlation between LATS2 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). LATS2 expression was examined in 73 NSCLC clinical specimens and 22 normal lung tissues using immunohistochemistry. Low levels of LATS2 protein were inversely associated with the T classification (P=0.001), N classification (P=0.005) and clinical stage (P=0.001) in NSCLC patients. Patients with lower LATS2 expression had a significantly shorter overall survival than patients with high LATS2 expression. Multivariate analysis suggested that low expression of LATS2 was an independent prognostic indicator (P=0.002) for the survival of patients with NSCLC. Furthermore, overexpression of LATS2 resulted in mobility inhibition in NSCLC cell lines A549 and H1299, and reduced protein level of matrix metalloproteinase-2 (MMP-2) and MMP-9. On the contrary, LATS2 siRNA treatment enhanced cell mobility and increased MMP-2 and MMP-9 protein expression level. In conclusion, low expression of LATS2 is a potential unfavorable prognostic factor and promoted cell invasion and migration in NSCLC.