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âConsiderable attention has been directed towards cyclodextrins (CDs) in the creation of co-assembled CPL-active materials, owing to their intrinsic chiral host cavities and synergistic host-guest interactions. However, achieving reversed CPL emission regulation with single-handedness CDs moiety poses a significant challenge. In this study, we have devised a series of γ-CD-based host-guest complexes comprising dual pyrene imidazolium derivatives with multiple linkers, which exhibit reversed circularly polarized emission. We have uncovered that the transformation of excimer stacking within γ-CD/pyrene complexes contributes to the inverted CPL emissions originating from a single-handed chiral host. This research elucidates the phenomenom of (+)- and (-)-circularly polarized excimer emission (CPEE) within γ-CD, arising from right- and left-handed stacking conformations, respectively.
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This study evaluated the structural characteristics, processing properties, and antioxidant properties of hydrolysates prepared from donkey milk (DM) whey protein using different proteases (Alcalase, Neutrase, papain, and Flavourzyme). The results showed that enzymatic hydrolysis significantly increased hydrolysate solubility and reduced average particle size compared to those of DM whey protein. Neutrase and Flavourzyme hydrolysates exhibited higher degrees of hydrolysis (DH), along with elevated emulsification properties and surface hydrophobicity. The choice of protease influenced secondary and tertiary protein structures and amino acid composition. Enzymatic hydrolysis led to decreased molecular weight of DM whey proteins. Moreover, all hydrolysates exhibited higher fluorescence intensity at λmax compared to DM whey protein, implying distinct properties due to the varied impacts of the four proteases on DM whey protein structure. The preparation of hydrolysates from DM whey proteins using proteases contributes to the development of integrated-value DM products.
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Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.
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Neoplasias Esofágicas , Aprendizado de Máquina , Análise Espectral Raman , Máquina de Vetores de Suporte , Análise Espectral Raman/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Humanos , Análise Discriminante , Análise de Componente Principal , AlgoritmosRESUMO
BACKGROUND: Accumulation studies found that tumor-associated macrophages (TAMs) are a predominant cell in tumor microenvironment (TME), which function essentially during tumor progression. By releasing bioactive molecules, including circRNA, small extracellular vesicles (sEV) modulate immune cell functions in the TME, thereby affecting non-small cell lung cancer (NSCLC) progression. Nevertheless, biology functions and molecular mechanisms of M2 macrophage-derived sEV circRNAs in NSCLC are unclear. METHODS: Cellular experiments were conducted to verify the M2 macrophage-derived sEV (M2-EV) roles in NSCLC. Differential circRNA expression in M0 and M2-EV was validated by RNA sequencing. circFTO expression in NSCLC patients and cells was investigated via real-time PCR and FISH. The biological mechanism of circFTO in NSCLC was validated by experiments. Our team isolated sEV from M2 macrophages (M2Ms) and found that M2-EV treatment promoted NSCLC CP, migration, and glycolysis. RESULTS: High-throughput sequencing found that circFTO was highly enriched in M2-EV. FISH and RT-qPCR confirmed that circFTO expression incremented in NSCLC tissues and cell lines. Clinical studies confirmed that high circFTO expression correlated negatively with NSCLC patient survival. Luciferase reporter analysis confirmed that miR-148a-3p and PDK4 were downstream targets of circFTO. circFTO knockdown inhibited NSCLC cell growth and metastasis in in vivo experiments. Downregulating miR-148a-3p or overexpressing PDK4 restored the malignancy of NSCLC, including proliferation, migration, and aerobic glycolysis after circFTO silencing. CONCLUSION: The study found that circFTO from M2-EV promoted NSCLC cell progression and glycolysis through miR-148a-3p/PDK4 axis. circFTO is a promising prognostic and diagnostic NSCLC biomarker and has the potential to be a candidate NSCLC therapy target.
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Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologia , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Microambiente TumoralRESUMO
Background: The early surgical intervention for pulmonary ground-glass nodules (GGNs) has become increasingly important, but accurate identification of these nodules during thoracoscopic surgery poses challenges due to the need for sublobar resections and reliance on visual and tactile perception alone. The prognosis of the procedure is closely tied to the use of precise positioning technology. Thus, it is crucial to develop an accurate positioning technology that can improve patient prognosis. Methods: Clinical data from the cardiothoracic department of a tertiary hospital in Shanghai were collected and analyzed between January 2020 and December 2021. The patients were categorized into 2 groups: an indocyanine green (ICG) group and a hook-wire group. Outcome measures including success rate, complications, procedure time, localization-related pain, and interval time were assessed. Adverse events and reactions were reported and compared between the 2 groups. Results: A total of 62 patients (17 males and 45 females, aged 50.5±13.2 years) were in the ICG group, while 66 patients (23 males and 43 females, aged 48.4±12.9 years) were localized in the hook-wire group. The success rate was comparable between the 2 groups. However, the ICG group showed significant advantages over the hook-wire group in terms of procedure time (22.6±4.4 vs. 24.1±4.9 min; P=0.012), localization-related pain (P<0.001), and interval time [median and interquartile range (IQR): 3 (0.7, 104.9) vs. 1.2 (0.5, 3.3) h; P<0.001]. In the ICG group, there were 11 cases of pneumothorax, 4 cases of hemothorax, and 2 cases of ICG diffusion. In the hook-wire group, there were 24 cases of pneumothorax, 25 cases of hemothorax, and 2 cases of dislodgement. The ICG group had fewer complications, including pneumothorax (P=0.018) and hemothorax (P=0.007), compared to the hook-wire group. Conclusions: Computed tomography (CT)-guided intrapulmonary injection of ICG for preoperative localization of peripheral pulmonary GGNs is a practical and safe technique. It offers advantages in terms of reduced procedure time, localization-related pain, and interval time compared to the hook-wire method. Moreover, the ICG technique results in fewer complications, making it a valuable preoperative localization technique worthy of popularization.
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AIMS: DEAD-box helicase 1 (DDX1) has oncogenic properties in several human cancers. However, the clinical significance and biological role of DDX1 in non-small cell lung cancer (NSCLC) remain elusive. Here, we examined the chemotherapeutic relevance of DDX1 in NSCLC. MAIN METHODS: We used the UALCAN database, Western blot analysis, and immunohistochemical and RT-qPCR assays to assess DDX1 expression in NSCLC cell lines (H1650 and A549) and patient tissues. The role of DDX1 in the chemosensitivity of NSCLC cells and the underlying mechanisms were determined using colony formation, CCK-8, flow cytometry, wound healing, Transwell, tumor sphere formation, and immunostaining assays, together with a xenograft tumor model in nude mice. KEY FINDINGS: Our study revealed that DDX1 was overexpressed in NSCLC cell lines and tissues. We further found that depleting DDX1 increased the sensitivity of NSCLC cells to the chemotherapy drug cisplatin, increased cell apoptosis, and inhibited cell migration and invasion. Co-immunoprecipitation assays revealed that DDX1 bound to ADAR1, and increased ADAR1 protein expression. Furthermore, we found that ADAR1 mediated cancer-promoting effects, independent of deaminase activity, by binding to RAC3 mRNA. Our findings not only show that DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis but also highlight the importance of ADARs as essential RNA-binding proteins for cell homeostasis, as well as cancer progression. SIGNIFICANCE: Our results suggest that DDX1 plays an important role in the development and progression of human NSCLC and that DDX1 may serve as a therapeutic target in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Animais , Humanos , Camundongos , Adenosina Desaminase/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisplatino/farmacologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismoRESUMO
Background: Currently, the anti-Nuss operation is widely used as standard surgery for pectus carinatum, but the installation and removal of the Nuss steel bars can be difficult, time-consuming and traumatic. To further simplify the procedure, we designed a new steel bar to facilitate minimally invasive surgical correction of pectus carinatum. Methods: From January 2018 to July 2021, 112 patients underwent minimally invasive repair of pectus carinatum (MIRPC) with the new steel bar in our centre. Two generations of bars were designed during our study period, and symmetric and asymmetric deformities were treated. After 2 years of follow-up, the bar and stabilizers were removed. The effects and complications of minimally invasive repair using the new bar to correct pectus carinatum were reviewed. Results: The mean patient age was 14.46 years. The mean operation duration was 67.74 minutes. The mean hospital length of stay was 3.64 days. The Haller index of the patients improved from 1.96 preoperatively to 2.78 postoperatively. The complications included pneumothorax, pleural effusion, wound infections, nickel allergy, screw loosening, wire breakdown, bar fraction and overcorrection leading to excavatum. Seventy-two patients (64.3%) underwent bar removal, with 63 patients (87.5%) achieving excellent or good results. The deformity recurred in 2 patients (2.8%) during follow-up. Conclusions: MIRPC with our newly designed steel bar can achieve good results and is effective in repairing both symmetric and asymmetric carinatum deformities.
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Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The role of circRNA in esophageal squamous cell carcinoma (ESCC) is largely unclear. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. Then the differentially expressed circRNA between ESCC and adjacent normal tissues were investigated using Rt-qPCR. The role of circ-ARAP2 expression on tumor progression were detected in both in vivo and in vitro. Luciferase reporter assays were used to identify the relationships among circ-ARAP2, microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). The result of the expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in both ESCC tissues and cell lines. Downregulation circ-ARAP2 suppressed ESCC proliferation, tumor growth and metastasis in both in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 restored ESCC cell proliferation and invasion ability after silencing circ-ARAP2. The study also found that circ-ARAP2 influenced the endothelial-mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Proteína Forkhead Box M1/genética , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Circular/genéticaRESUMO
Nonvolatile compounds usually have a high molecular weight and exhibit a high boiling point, which poses great challenges to the ionization method of MS. Ambient ionization sources can efficiently analyze the nonvolatile compounds without complex pretreatment, but they generally require special media such as heating devices, laser optical devices, or corona needles. Acoustic nebulization assisted photoionization (ANPI) is a potential method for the analysis of nonvolatile compounds that uses nebulization as a prerequisite for photoionization and introduces many advantages of PI, including excellent ionization efficiency, a high yield of molecular ions, and simplified spectrum interpretation. However, the ANPI source can be limited in on-site applications by the complexity of the analytical devices and the high cost of the nebulization chip. To address this issue, in this paper, we explored cheap and commercially piezoelectric materials used in a mist sprayer and fabricated a nebulization swab assisted photoionization (NSAP) as an ambient ionization source. Some useful results are presented: numerical simulation was introduced successfully for optimizing the aerosol distribution in the NSAP source; nonvolatile muscle relaxants, drugs of abuse, antibiotics, phthalates, and cholesterol were detected mostly as their protonated molecular ions while some special acetone/water cluster ions were detected. In addition, the LOD for most of the target analytes ranged from 10.0 to 50.0 pg with RSD ≤ 9%. Finally, this method is implemented for Chinese baijiu spiked with phthalates. The experimental data shows the capability of a NSAP source in high sensitivity and on-site analysis of the nonvolatile compounds.
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Acetona , Acústica , Cromatografia Gasosa-Espectrometria de Massas , Íons , Espectrometria de Massas/métodosRESUMO
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, which is a severer threaten to human health because of its extremely high morbidity and mortality. In this study, the role of Notchless homolog 1 (NLE1) in the development of NSCLC was investigated and the underlying mechanism was explored. The outcomes showed that NLE1 expression is significantly higher in tumor tissues than normal tissues, and is correlated with the pathological stage. The regulation of NSCLC development by NLE1 was also visualized by the in vitro and in vivo loss-of-function studies, which indicated the inhibition of cell growth and migration, as well as enhancement of cell apoptosis on condition of NLE1 knockdown. As for the mechanism, it was demonstrated that NLE1 may execute its tumor-regulating function through activating E2F1-mediated transcription of CDK1, and PI3K/Akt signaling pathway was also supposed as a downstream of NLE1 in the regulation of NSCLC. Both CDK1 overexpression and treatment of Akt pathway activator could reverse the NLE1 knockdown induced NSCLC inhibition to some extent. In conclusion, this study identified NLE1 as a novel tumor promotor in the development and progression of NSCLC, which may be a potential therapeutic target in the treatment of NSCLC.
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OBJECTIVES: Pectus excavatum (PE) can be secondary in patients who underwent sternotomy for cardiac surgery. Retrosternal adhesions increase the complexity and risk of traditional Nuss repair. Thus, we summarized the outcomes of our modified Nuss procedure using a newly designed bar. METHODS: A retrospective analysis was performed on 35 patients who underwent modified PE repair after open heart surgery from January 2011 to July 2019. The surgery was performed using a novel bar with no need for intraoperative reshaping and rotation, assisted by thoracoscopy and subxiphoid incision when necessary. RESULTS: There were 19 males and 16 females with a median age of 5.3 years (interquartile range, 4.1-10.9) at PE repair. All patients underwent the modified procedure uneventfully with no death. The median operating time was 70 min. Twenty-nine (82.9%) patients required subxiphoid incision assistance. There was 1 case (2.8%) with unexpected sternotomy due to intraoperative bleeding. The median length of postoperative hospital stay was 4 days. During the median 3.5 years of follow-up, no bar dislocation was found and 30 (85.7%) patients had their bars removed with no recurrence recorded. After PE repair, the Haller index improved significantly (2.6 ± 0.4 vs 4.9 ± 1.3, P < 0.05) and further decreased till the time of bar removal (2.5 ± 0.4 vs 2.6 ± 0.4, P < 0.05). All patients were satisfied with the cosmetic outcome. CONCLUSIONS: The novel bar can be placed and removed easily with a low rate of adverse events. This modified Nuss procedure seems to be a safe, effective and convenient approach for the management of PE after cardiac surgery.
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Tórax em Funil , Cardiopatias Congênitas , Pré-Escolar , Feminino , Tórax em Funil/complicações , Tórax em Funil/cirurgia , Cardiopatias Congênitas/cirurgia , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Aço , Resultado do TratamentoRESUMO
LncRNAs play an important role in tumorigenesis and progression; however, the function and mechanisms of lncRNAs in esophageal cancer (EC) remain largely unclear. In this study, we screened the differentially expressed lncRNAs in EC by using RNA-seq and one of the most upregulated lncRNAs, lncRNA RP11-465B22.8, was further characterized. LncRNA RP11-465B22.8 was upregulated in EC tissues and high lncRNA RP11-465B22.8 expression was associated with poor survival of EC patients. Ectopic expression of lncRNA RP11-465B22.8 enhanced the proliferation, migration, and invasion of EC cells, whereas knockdown of lncRNA RP11-465B22.8 led to the opposite effects. Mechanistically, lncRNA RP11-465B22.8 sponged miR-765 to increase the expression of KLK4. Moreover, LncRNA RP11-465B22.8 could be delivered from EC cells to macrophages via exosomes and subsequently induced M2 macrophage-induced cell migration and invasion. Our findings revealed a novel lncRNA RP11-465B22.8/miR-765/KLK4 pathway in EC and indicated that lncRNA RP11-465B22.8 might be a potential target for EC therapy.
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BACKGROUND: Shortcoming of traditional Nuss operation on adults is gradually found in the clinical practice. A new kind of introducer-bar complex was introduced. However, there is limited evidence regarding its safety and efficacy. Therefore, a single center, retrospective study was conducted to address this issue. METHODS: Patients with pectus excavatum who underwent surgery between January 2015 and June 2017 were consecutively enrolled in this study. In all, 52 patients underwent the modified procedure using the introducer-bar complex (new procedure group), whereas 48 underwent the traditional anti-Nuss procedure (traditional procedure group). Outcomes analysis of balanced baseline was performed to compare the intraoperative and postoperative short-term outcomes. RESULTS: All patients in the new procedure group had shorter operation duration (51.54 ± 20.32 vs. 79.45 ± 13.88 min, p = 0.017), postoperative hospitalizations (4.77 ± 1.62 vs. 6.86 ± 2.18 days, p = 0.028), plate removal surgery durations (39.30 ± 8.97 vs. 60.30 ± 10.49 min, p < 0.001), and less blood loss during operation (6.25 ± 4.88 vs. 10.90 ± 5.75 ml, p = 0.003) than patients in the traditional procedure group. There was no significant difference in the length of incision, postoperative Haller index, cost, number of steel bars, postoperative surgical outcome and incidence of complications between the two groups. CONCLUSION: Through the main clinical outcome were similar, our results shown that modified procedure may have the shorter operation time, postoperative hospital stay, and operation time for plate removal and less blood loss, which may bring potential clinical benefits to patients.
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Tórax em Funil , Adulto , Tórax em Funil/cirurgia , Humanos , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Long noncoding RNAs (lncRNAs) are known to exert their effects to tumor progression. In this study, the role of the lncRNA GAS5 (growth arrest specific 5) was confirmed in reducing non-small cell lung cancer (NSCLC) cisplatin (DDP) resistance. In NSCLC tissue samples, GAS5 expression decreased significantly. Low GAS5 levels were positively correlated with NSCLC characteristics including TNM, tumor size and lymphatic metastasis. Functionally, GAS5 significantly reduced NSCLC/DDP cell migration, invasion and epithelial-mesenchymal transition (EMT) progression in vitro. In vivo, GAS5 upregulation inhibited remarkably NSCLC/DDP cell tumor growth. Mechanism analysis suggested that GAS5 was a molecular sponge of miR-217, inhibiting the expression of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). In conclusion, this study reveals that the GAS5/miR-217/LHPP pathway reduces NSCLC cisplatin resistance and that LHPP may serve as a potential therapeutic target for NSCLC cisplatin resistance.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pirofosfatase Inorgânica/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Camundongos , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Limited data exist for adults with recurrent pectus excavatum (PE) treated with minimally invasive surgical repair. METHODS: Between July 2008 and December 2020, forty-two adult patients with recurrent PE underwent a modified Nuss procedure with a newly designed bar in our center. A small vertical subxiphoid incision was used to separate severe adhesions when necessary. Multiple steel wires were sutured, and the rib space was narrowed to firmly fix the bar. The primary end point was Haller index change after operation. The secondary end points included length of stay after operation, short-term and long-term complications. RESULTS: The mean patient age was 22.02 ± 3.49 years. The mean Haller index was 4.59 ± 1.09. A subxiphoid incision was performed in 12 patients. Thirty-nine patients had one bar placed, and 3 patients required two bars. Sixteen patients had 3 or more wires fixation, and 4 patients needed to have their intercostal space narrowed. There was no perioperative death, and the mean hospitalization was 5.57 ± 2.47 days. The Haller index reduced to 3.03 ± 0.41 after the operation (t = 11.85, p < 0.001). During the follow-up, there were 3 patients who developed non-infective wound effusion; bar rotations occurred in 3 patients. Twenty patients had the bar removed, post-bar removal Haller index was significantly reduced compared to the preoperative Haller index (2.89 ± 0.37 vs. 4.72 ± 1.05, t = 8.96, p < 0.001). CONCLUSIONS: The modified Nuss procedure with a new titanium alloy bar can achieve good results for adult patients with recurrent PE.
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Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm2) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo. Our data demonstrates that ASS promotes exosome and autophagy components releasing in a time dependent manner, inhibition of exosome release exacerbates ASS induced NSCLC cell apoptosis. Furthermore, we identified that this function was regulated by sirtuin 2 (SIRT2). And, RNA immunoprecipitation (RIP) assay suggested SIRT2 directly bound to the 3'UTR of transcription factor EB (TFEB) and facilitated its mRNA stability. TFEB is a key transcription factor involved in the regulation of many lysosome related genes and plays a critical role in the fusion of autophagosome and lysosome. Altogether, this data revealed that SIRT2 is a mechanical sensitive protein, and it regulates ASS induced cell apoptosis by modulating the release of exosomes and autophagy components, which provides a promising strategy for the treatment of NSCLCs.
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Accumulating studies suggest that circular RNAs (circRNAs) function as key regulators in human cancers. We found that hsa_circ_0001869 participated in non-small cell lung cancer (NSCLC) progression. However, its expression and function during NSCLC remain unknown. The data advised that hsa_circ_0001869 expression was increased in NSCLC cell lines and tissues. High hsa_circ_0001869 expression had negatively correlation with the NSCLC patients prognosis. Bioinformatics and luciferase report analyses confirmed that miR-638 and FOSL2 were hsa_circ_0001869 downstream target. hsa_circ_0001869 downregulation decreased tumor proliferation, invasion and migration by promoting miR-638 expression and decreasing FOSL2 expression. As a result of overexpression of FOSL2 or silencing of miR-638, the recovery of proliferation, migration, and invasion after hsa_circ_0001869 silencing. Overexpression of FOSL2 also led to recovery of migration, invasion and proliferation after upregulation of miR-638. In vivo studies confirmed that overexpression of FOSL2 or silencing of miR-638 led to the recovery of tumor growth ability regarding A549 cells after hsa_circ_0001869 knockdown. Present investigation discovered that hsa_circ_0001869 enhanced NSCLC progression via sponging miR-638 and promoting FOSL2 expression. hsa_circ_0001869 downregulation suppressed tumor growth and invasion ability.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Antígeno 2 Relacionado a Fos/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Circular/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Biologia Computacional , Bases de Dados Genéticas , Progressão da Doença , Feminino , Antígeno 2 Relacionado a Fos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Circular/genética , Transdução de Sinais , Carga TumoralRESUMO
Circular RNAs (circRNAs) belong to non-protein-coding RNAs that regulate different pathophysiological procedures. Upregulation of hsa_circ_0020123 is found in non-small cell lung cancer (NSCLC); however, its activity and functions are not clear. In this study, the results showed that hsa_circ_0020123 expression increased in both tumor tissues and NSCLC cells. A higher hsa_circ_0020123 expression also led to poor prognoses among NSCLC patients assayed via FISH. The data of FISH also confirmed that hsa_circ_0020123 primarily had a cytoplasmic location. Hsa_circ_0020123 knockdown caused a significant decrease in nude mouse xenograft growth. Bioinformatics analyses and dual luciferase reporter assays confirmed that hsa_circ_0020123 was an miR-495 sponge and that the HOXC9 gene was a miR-495 target. The miR-495 downregulation reversed cell migration and proliferation inhibition induced by hsa_circ_0020123 silencing in vitro. HOXC9 overexpression reversed miR-495-induced inhibition of cell migration and proliferation. The dual luciferase reporter assay demonstrated that hsa_circ_0020123 interacted with miR-495 by binding to the HOXC9 3'-UTR to suppresses post-transcriptional HOXC9 expression. Taken together, our study found that hsa_circ_0020123 functioned like a tumor promoter via a novel hsa_circ_0020123/miR-495/HOXC9 axis, highlighting its possibility as a new NSCLC therapeutic target.
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Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G0-G1 phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G1 phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis.
Assuntos
Ciclo Celular , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Neoplasias Pulmonares/patologia , Fator de Transcrição STAT6/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular , Inibidor de Quinase Dependente de Ciclina p27/genética , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Fator de Transcrição STAT6/genética , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Introduction: The anti-Nuss procedure has gradually been found to have several shortcomings in clinical practice. Accordingly, our department previously designed and introduced a new steel plate. However, there is limited evidence regarding its safety and efficacy. Thus, we aim to compare the efficacy and safety of the conventional anti-Nuss operation with those of a modified anti-Nuss operation using a flexible plate. Methods: Patients with pectus carinatum who underwent surgery between January 2014 and August 2019 were consecutively enrolled in this single-center, retrospective study. In all, 53 patients underwent the modified procedure using the new steel plate (new procedure group), whereas 43 underwent the conventional anti-Nuss procedure (traditional procedure group). Outcome analysis was performed using SPSS to compare the intraoperative and postoperative short-term outcomes. Results: All patients in the new procedure group had shorter operation duration (75.23 ± 11.90 vs. 82.45 ± 9.30 min, p = 0.008), postoperative hospitalizations (3.42 ± 0.95 vs. 4.64 ± 1.53 days, p = 0.039), and plate removal surgery durations (40.60 ± 3.47 vs. 60.30 ± 9.75 min, p = 0.041) than patients in the traditional procedure group. There were no significant differences in the length of incision, postoperative Haller index, cost, postoperative surgical outcome, and incidence of complications between the two groups. Conclusion: Our data reveal that the main clinical outcomes were similar for after anti-Nuss operation and modified anti-Nuss operation. However, the modified procedure for pectus carinatum had a shorter operation duration, postoperative hospitalization, and plate removal surgery duration.